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TABLE OF CONTENTS

PAGE

INTRODUCTION.. ..................... .i

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MEDICAL EXPE;RIMEZNT MOO1 Cardiovascular Conditioning
Lawrence F. Dietlein, M.D., NASA, Manned Spacecraft
. . .1 /t

Center
W i l l i a m V. Judy, NASA, Manned Spacecraft Center

.
MEDICAL EXPERIMENT MOO3 In-Flight Exerciser
Lawrence F. Dietlein, M.D., NASA Manned Spacecraft
. . . . . . . 37 J’
Center
R i t a M. Ram, NASA Manned Spacecraft Center

MEDICAL EXPERIMENT MOO4 .In-Flight Phonocardiogram


C. Vallbona, M.D., Baylor University College of
. . . . 49 v /
Medicine
Lawrence F. Dietlein, MODe, NASA, Manned Spacecraft
Center

Fluids . . . . . . .- . . . . . . . . . . . . . . . . .
MEDICAL EXPERIMENT MOO5 Biochemical Analysis of Body

H a r r y S. Lipscomb, M.D., Baylor Uaiversity College of


6~
Medicine
E l l i o t H a r r i s , Ph.D., NASA, Manned Spacecraft Center
Lawrence F. Dietlein, M.D., NASA Manned Spacecraft Center

MEDICAL EXPERIMENT MOO6 .


Bone Demineralization . . . . . . 83
IJ
Pauline Beery Mack, Ph.D., Texas Womanb University
Paul A. LaChance, Ph.D., NASA Manned Spacecraft Center
George P. Vose, Ph.D., Pennsylvania S t a t e University
Fred B. Vogt, M.D., University of m a s

.
MEDICAL EXPERIMENT MOO7 Calcium Balance Study . . . . . . 127
G. Donald Whedon, W.D., National I n s t i t u t e s of Health
J
Leo Lutwak, M.D., Caornell University
W i l l i a m Reurnan, M.D., University of Rochester
TABLE OF COMTplNTs
(Continued)

PAGE

MEDICAL EXPERIMEPf MOO8 -


In-Flight Sleep Analysis
Peter Kellway, Ph.D., Baylor University College of
. . . . . . 167
Medicine
Robert L. Maulsby, M.D., Baylor University College of
Medicine

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MEDICAL EXP~IMEWfMOO9 Human Otolith Function
Ashton Grwbiel, M.D.,
a. . . . . 191
Naval Aerospace Medical I n s t i t u t e
J
Ear1 F. Miller, Naval Aerospace Medical I n s t i t u t e

AND CONCLUSIONS CONCERNING MEDICAL RESULTS OF


SU~VIMARY
TKE GEMINI V I 1 MANHEXI SPACE FLIGHT
. 251 J’
Charles A. Berry, M.D., Director, Medical Research and
Operations, NASA Manned Spacecraft Center

SUMMARY OF MEDICAL EXPEXIMENTS PROGRAM REVIEW OF FINDINGS


THROUGH GEMINI VI1
S. P. Vinograd, M.D., Director, Medical Science and
. . 281 J
Technology, NASA Headquarters
On August 23, 1966, a review of the medical findings of
the fourteen day Gemini 7 mission and related f l i g h t s was

conducted.

This review was organized at the request of Dr. George E.

Mueller, Associate Administrator f o r Manned Space Flight, and


consisted of presentations by the P r i n c i p d Investigators OT

the Gemini Medical Flight Experiments and by the Director,

Medical Research and Operations, Manned Spacecraft Center.

This document is a campilation of t h e material presented at

t h e review. The Principals cooperated most significantly by

reviewing a transcription of atape recordlng of t h e i r presenta-

tion, e d i t i n g and providing a final version f o r publication.

Without t h i s most generous assistance, this document could not

have been published.

-le I, which follows immediately after t h i s Introduction,

is presented t o acquaint the reader w i t h the scope and sequence

of medical measurements and experiments w h i c h were conducted during


Project Gemini. This review was held prior t o the conduct of the

G e m i n i 11 and 12 missions, therefore, m a t e r i a l derived from those


GratefuL acknawledgement is given to Miss Joyce M. Patterson,
Space Medicine, for her efforts in compiling the final papers and

preparing the material for publication.

Biomedical Prograrn Specialist


Space Medicine
b133DICAJ,3 EXPERIMWrS/-S CONDUCTED ON FLIGHT CREWS
-
DURING PROJECT GEMINI
-
% 3
'3:= 79
$9
ss
=#=
Frn 3 "

1;2
0s
p3
3%

IN-FLIGHT 3d
7 -
brn gg --
R
MOO1 -
Cardiovascular X X 2
Conditioning - 9
MOO3 -
Ln-Flight
Bcerciser
X X 3

MOO4 -
Ih-Fligh% X X 3
Phonocardiogram
-
MOO5 Bioassays Body X 2
Fluids
~ 0 0 6- %ne mminera- X X 3
l i z a t ion

~ 0 0 7- Calcium Bslanc X 1
Study
-
~ 0 0 8 In-Flight Slee
Analysis
X 1

MOO9 - H ~ m a nOtolith X X 1
Function
He& Rate X X X X X 10

Respiration Rate X X X X X 10

Blood Pressure X X 5
O r a l Temperature X X X A A 7
PRE AND POST FLIGHT,
T i l t Table I: x X X X 10

Hematologp X X X X X 10
A. Blood Volume X X X X 6
B. RBC Indices X X X X 5
C. Reticulocyte C o a t X X X X 5
Urine* X X X X 9
Exercise m l e r s n c e X X X X 5
X X x X X 8
Body Weight

A = Available; # = To Nearest Hour;


/=
- -
Pre-Flight Only
- -
*Stmda.rd blood and u r i n e examinations, physical exambations and verbal debriefings
followed each f l i g h t .
iii
Medical Experiment MOO1

CARDIOVASCULAR CONDITIONING

Principal Investigators:

Lawrence F. Metlein, M.D.


Chief, Biomedical Research Office
NASfl M a n n e d Spacecraft Center
Houston, Texas

William V. Judy
Biomedical Research O f f ice
NASA Manned Spacecraft Center
Houston, Texas
EXPERIMENT M-1, CARDIOVASCULAR CONDITIONING

BY
Lawrence F. Dietlein, M.D.
Chief, Biomedical Research Office

NASA Manned Spacecraft Center

and
William V. Judy

Biomedical Research Office


NASA Manned Spacecraft Center

INTRODUCTION

Ground baseline studies in support of Experiment M-l indicated

that leg cuffs alone, when inflated to 70 to 75 millimeters of mercury

for 2 out of every 6 minutes, provided protection against cardiovascu-

which was occasioned by 6 hours of water immersion


lar lldeconditioningrl
(ref. 1). Four healthy, male subjects were immersed in water to neck
level for a 6-hour period on two separate occasions, 2 days apart.

Figures 39-1, 39-2, 39-3, and 39-4 indicate that 6 hours of water
immersion resulted in cardiovascular "deconditioning", as evidenced

by cardioacceleration in excess of that observed during the control


tilt and by the occurrence of syncope in two of the f o u r subjects,

The tilt responses following the second period of imersion, during

which leg cuffs were utilized, revealed that a definite protective

effect was achieved. Cardioacceleration was less pronounced, and

no syncope occurred.

2
The physiological mechanisms responsible for the observed efficacy

of the cuff technique remain obscure. One might postulate that the
cuffs prevent thoracic blood volume overload, thus inhibiting the so-
called Gauer-Henry reflex with its resultant diuresis and diminished

effective circulating blood volume. Alternatively, or perhaps addition-


ally, one might postulate that the cuffs induce an intermittent artifi-

cial hydrostatic gradient (by increasing venous pressure distal to the


cuffs during inflation) across the walls of the leg veins, mimicking

the situation that results from standing erect in a 1-g environment and

thereby preventing the deterioration of the normal venomotor reflexes.

Theoretically, this action should lessen the pooling of blood in the

lower extremities and increase the effective circulating blood volume

upon return to a 1-g environment following weightlessness or its simu-


lation. The precise mechanism, or mechanisms, of action must await

further study.

EQUIPMENT AND METHODS

The equipmenc used in Experiment M-1 consisted of a pneumatic


timing or cycling system and a pair of venous pressure cuffs (figs. 39-5

and 39-6). The cycling system was entirely pneumatic and alternately
inflated and deflated the leg cuffs attached to the pilot's thighs. The

system flown on Gemini V (fig. 39-7) consisted of three basic components:

(I) A pressurized storage vessel charged with oxygen to 3500 psig.


(2) A pneumatic control system for monitoring the pressurized
storage vessel.

3
(3) A pneumatic oscillator system for periodically inflating and
deflating the leg cuffs.
The equipment flown on Gemini VI1 was almost identical with that,used on

Gemini V and was supplied with oxygen pressure from the spacecraft

environmental control system. The pneumatic venous pressure cuffs


were formfitted to the proximal thigh area of the pilot. The cuffs
consisted essentially of a 3- by 6-inch bladder enclosed in a soft

nonstretchable fabric. The bladder portion of each cuff was positioned


on the dorsomedial aspect of each thigh. The lateral surface of the

cuffs consisted of a lace adjuster to insure proper fit.

RESULTS

The Cardiovascular Conditioning Experiment (M-1) was flown on the


GeminiV and VI1 missions, The pilots for these missions served as

experimental subjects; the command pilots were control subjects. The

experiment was operative for the first 4 days of the 8-day Gemini V
mission, and 13.5 days of the Gemini VI1 mission.
Prior to these missions, each crewmember was given a series of

tilt-table tests. These control tilts are summarized in table 39-1,


the numerical values indicated being mean values for the three control

tilts, The results of six consecutive postflight tilts for the Gemini V
command pilot and pilot are summarized in figures 39-8 and 39-9. Figure

39-10 summarizes the heart-rate change during the initial postflight


tilt expressed as a percent of the preflight value for all the Gemini

flights to date. The results of four consecutive postflight tilts for

4
the Gemini VI1 command pilot are indicated in figures 39-ll through

39-14, and f o r the Gemini VI1 pi1,pt in figures 39-15 through 39-18.
Figure 39-19 summarizes the Gemini VI1 tilt-table data,

The crewmembers f o r both the Gemini V and VI1 missions exhibited

increased resting pulse rates during the first 12 to 24. hours after

recovery. Resting pulse rate changes f o r both crews are indicated


as deviations from the preflight mean values in table 39-11.

The Gemini V crew exhibited a higher postflight mean resting


pulse rate than did the Gemini VI1 crew, with a maximal difference

of 2-fold (pilot's) occurring 2 to 4 hours after recovery. This

elevated resting pulse rate gradually returned to the preflight levels.

The Gemini VI1 crew exhibited a slight increase in postflight mean


resting pulse rate over preflight levels; these values returned to

preflight levels approximately 24 hours after recovery. The crewmem-


bsrs for both Gemini V and VI1 exhibited changes in their resting
systolic and diastolic blood pressures after the missions. These

values are indicated as deviations from the preflight mean values in


table 39-111 e

A l l crewmembers had a decreased resting systolic blood pressure

2 to 4 hours after recovery, The Gemini V command pilot and the

Gemini VI1 pilot maintained a lower-than-preflight systolic pressure

throughout the postflight test period. All crewmembers exhibited a

decreased resting diastolic blood pressure during each postflight

tilt test except during the first and last tilts for the Gemini V
command pilot, and during the second tilt for the Gemini VI1 pilot.

5
Daily changes i n r e s t i n g blood pressures a r e indicated i n f i g u r e s 39-9

and 39-19 a s deviations from t h e p r e f l i g h t mean values.

During t h e p o s t f l i g h t t i l t s , a l l t h e Gemini V and VI1 crewmembers

exhibited incressed pulse r a t e s , Highest r a t e s were observed during

the t i l t s performed 2 t o 4 hours a f t e r recovery. Pulse r a t e increases

over p r e f l i g h t mean values f o r each p o s t f l i g h t tilt a r e indicated i n

t a b l e 39-IV.

The Gemini V crew exhibited a twofold greater increase i n pulse r a t e

than did t h e Gemini V I 1 crew during t h e f i r s t two p o s t f l i g h t t i l t s .

Although t h e Gemini V I 1 crew sustained a smaller increase i n pulse r a t e

during the tilt procedures, the Gemini V I 1 p i l o t had t o be returned t o

t h e supine position a t t h e end of 1 2 minutes during t h e f i r s t tilt,

This syncopal response was of t h e vasodepressor type and i s i l l u s t r a t e d

i n figure 39-15. This untoward experience during the f i r s t tilt procedure

may account f o r h i s increased pulse r a t e during t h e second and t h i r d

tilts. The pulse r a t e s of a l l crewmembers decreased during succeeding

t i l t s t o near p r e f l i g h t l e v e l s ( f i g s , 39-8 and 39-19).


All crewmembers exhibited narrowed pulse pressures during t h e
f i r s t p o s t f l i g h t tilt (compared with t h e p r e f l i g h t tilt and t h e post-

f l i g h t r e s t i n g values). The Gemini V crew a l s o exhibited a marked

pulse pressure narrowing during t h e second (8 t o 1 2 hours) p o s t f l i g h t

tilt. The Gemini V command p i l o t maintained a low s y s t o l i c pressure


during t h e t h i r d and f o u r t h t i l t s , whereas t h e Gemini V p i l o t returned

t o normal p r e f l i g h t l e v e l s a f t e r t h e second p o s t f l i g h t tilt. The

Gemini V I 1 crew revealed no marked pulse pressure narrowing during

6
t h e i r second, t h i r d , or fourth p o s t f l i g h t t i l t s . The changes i n

s y s t o l i c and d i a s t o l i c pressures f o r both crews a r e indicated as

deviations from t h e p r e f l i g h t mean values i n t a b l e 39-V.

During the p o s t f l i g h t recovery phase, the blood pressure values

f o r t h e G e m i n i V and V I 1 crewmembers returned t o near p r e t i l t r e s t i n g

l e v e l s ( f i g s , 39-8 and 39-19). Leg volume changes during t h e post-

f l i g h t t i l t s i n d i c a t e t h a t the p i l o t s who wore t h e pneumatic suffs

did indeed pool s i g n i f i c a n t l y l e s s blood i n t h e i r legs during the

t i l t s than d i d t h e command p i l o t s . These values a r e indicated a t

percent increase above t h e p r e f l i g h t control values i n t a b l e 39-VI.

Although t h e Gemini V I 1 p i l o t exhibited a vasodepressor type

syncope during h i s first p o s t f l i g h t tilt, he did not pool an exces-

s i v e amount of blood i n h i s l e g s ( 2 percent above the p r e f l i g h t

control value). In addition, despite the f a c t t h a t the V and V I 1


command p i l o t s pooled similar q u a n t i t i e s of blood i n t h e i r l e g s

during the f i r s t p o s t f l i g h t tilt, they differed considerably i n the

volume pooled during t h e remaining t i l t s . These differences, a s well

a s those of t h e Gemini V p i l o t , may be a r e f l e c t i o n primarily of

differences i n tho, s t a t e of hydration.

Changes i n t o t a l blood volume, plasma volume, and red c e l l mass

were determined before and a f t e r f l i g h t , Radioactive isotope (I125

C r 51) techniques were u t i l i z e d i n these measurements. The r e s u l t s

a r e indicated a s percent c k n g e s i n t a b l e 39-VII.

The Gemini V I 1 crew sustained a 4- t o 15-percent increase i n

plasma volume during the U d a y mission, whereas the Gemini V crew

7
l o s t 4 t o 8 percent of t h e i r plasma volume during the $-day mission.

Both crews l o s t 7 t o 20 percent of t h e i r red c e l l mass. The Gemini V I 1

p i l o t , however, sustained only a 7-percent decrease a s compared with

the 19- t o 20-percent decrease of t h e other crewmembers. The decrease

i n red c e l l mass and t h e increase i n plasma volume of t h e Gemini V I 1

crew o f f s e t each other t o give a n e t zero-percent change i n t o t a l

blood volume, whereas the reduction i n plasma volume and t h e red c e l l

mass of the Gemini V crew contributed t o t h e measured 13-percent

decrease i n t o t a l blood volume. These changes i n t o t a l blood volume

may r e f l e c t , i n p a r t , t h e s t a t e of hydration of t h e Gemini V crew, but

t h i s i s not t r u e i n t h e case of t h e Gemini V I 1 crew. The p o s t f l i g h t

changes i n body weight a r e indicated i n t a b l e 39-VIII,

The Gemini V command pilot and p i l o t sustained a 7.5- and 8.5-

pound l o s s i n body weight, respectively. The Gemini V I 1 command p i l o t

and p i l o t l o s t 10.0 and 6.5 pounds, respectively. These values a r e

similar t o those observed a f t e r previous missions of shorter duration.

DISCUSSION

The f l i g h t conditions operative during t h e Gemini V I 1 mission

were notably d i f f e r e n t from those of t h e Gemini V f l i g h t . These

variables or differences were of s u f f i c i e n t magnitude t h a t a comparison

of the M-1 r e s u l t s on t h e two missions i s d i f f i c u l t , i f not $mpossible.

rsminiVI1 was decidedly d i f f e r e n t from previous Gemini f l i g h t s i n

t h a t t h e Gemini VI1 crew did not wear t h e i r s u i t s during an extensive

portion of t h e U - d a y Plight. Their food and water intake was more

8
nearly optimal than in previous flights; this assured better hydration

and electrolyte balance, and the Gemini VI1 exercise regimen was more
rigorous than that utilized on previous flights. These variables,
in addition to the usual individual variability always present, preclude
any direct comparison of M-1 results on the two missions. This is

particularly true since the pulsatile cuffs were operative during


only the first half of the 8-day Gemini V mission. The Gemini VI1

pilot's physiological measurements should be compared only with those


of the command pilot who served as the llcontrolll
subject.

It is indeed true that the postflight physiological responses

of the Gemini VI1 crew were vastly different from, and generally
improved over, those observed in the CeminiV crew. It is difficult,

however, to determine which of the previously mentioned variables

were responsible for the observed improvement, This improvement is

I perhaps best shown in figure 39-8, which depicts the change in heart

rate during the initial postflight tilts expressed as a percentage


1
?"I change with respect t o the preflight value. The responses of the
1

1 Gemini VI1 crew were far superior to the responses observed in the
1
4 1 Gemini IV and V crews, and they were very nearly comparable to the

response following 14. days of recumbency,

Additional comparisons between the Gemini VI1 and V crews may be

summarized as follows:

(1) The Gemini VI1 crew exhibited less increase in postflight


I
I mean resting pulse rate ( 4 and 10 beats per minute versus 21 and 59
I

3 beats per minute).

9
w
e

(2) The Gemini VI1 crew exhibited signs of o r t h o s t a t i c i n t o l e r -


ance f o r only 24 hours p o s t f l i g h t ; t h e Gemini V crew exhibited these

signs f o r 24 t o 48 hours.
( 3 ) The Gemini VI1 crew pooled less blood i n t h e i r lower extremi-
ties during a l l p o s t f l i g h t t i l t s .

( 4 ) The Gemini VI1 crew exhibited less pronounced changes i n


intravascular f l u i d volumes i n t h e p o s t f l i g h t period a s shown i n t h e

following:

(a) Total blood volume: 0 percent versus 13 percent,


I
(b) Plasma volume: i-15 percent and +4 percent versus -8
percent and -4 percent.

(c) Red c e l l mass: -19 percent and -7 percent Terms -20


percent and -20 percent,

( 5 ) The Gemini VI1 crew l o s t 10.0 pounds (command p i l o t ) and


6.5 pounds (pilot) during t h e i r f l i g h t , while t h e Gemini V crew l o s t
7.5 and 8.5 pounds, respectively.

(6) The Gemini VI1 crew regained less body weight during t h e
f i r s t 24. hours p o s t f l i g h t (40 percent and 25 percent versus 50 percent).
The physiological findings i n t h e Gemini V crew have been previously

reported ( r e f . 2) and w i l l only be summarized here.

(1) The p i l o t ' s r e s t i n g pulse r a t e and blood pressure returned


t o p r e f l i g h t r e s t i n g l e v e l s within 4.8 hours a f t e r recovery; t h e command
p i l o t required a somewhat longer period.
(3) The pilot's plasma volume decreased 4 percent, and the
command pilot's decreased 8 percent.

( 4 ) The pilot's body weight loss was 7.5 pounds; the command
pilot's was 8.5 pounds.

(5) The pooling of blood in the legs of the pilot was generally
less than that observed in the command pilot,
The observed differences between the Gemini V command pilot and
pilot probably reflect only individual variability and cannot be
construed as demonstrating any protective effect of the pulsatile
thigh cuffs. The Gemini V tilt data are summarized in figures 39-9

and 39-10.
Tilt-table data are graphically presented in figures 39-11

through 39-14.for thg command pilot and in figures 39-15 through

39-18 for the pilot. A l l the Gemini VI1 tilt data are summarized
in figure 39-19. During the first postflight tilt, the pilot exhibited
signs of vasodepressor syncope; the procedure was interrupted, and the

pilot was returned to the supine position. This episode occurred


despite the fact that there was no evidence of increased pooling of
blood in the lower extremities. In subsequent tilts, the pilot

exhibited no further signs of syncope or impending syncope. It is of


significance that this episode of syncope occurred despite the fact
that the measured blood volume of both crewmembers was unchanged from

preflight levels.

It would seem possible that this syncopal episode was the result
of sudden vasodilitation with pooling of blood in the splanchnic area,
diminished venous return, diminished cardiac output, and decline in
cerebral bloodflow.

As previously mentioned, there was no diminution in the total


blood volume of either crewmember after the mission. The pilot's

plasma volume increased 4 percent; the command pilot's increased 15

percent. The pilot's red cell mass decreased 7 percent; the command
pilot's, 19 percent. The pilot lost 6.5 pounds (nude body weight)

during the mission and replaced 25 percent of this loss during the
first 24. hours after recovery. The command pilot lost 10.0 pounds

and replaced 4.0 percent of this value within the first 24. hours
following recovery.

The pilot's subsequent tilts revealed a moderate cardioaccelera-

tion during tilts 2 and 3, with normal pulse pressure and insignificant

pooling of blood in the lower extremities (figs. 39-16, 39-17, and

39-18). The command pilot exhibited moderate cardioacceleration,

marked narrowing of the pulse pressure, and increased pooling of blood


in the lower extremities during the initial postflight tilt. Subse-

quent tilts revealed a rather rapid return to normal of heart rate


and pulse pressure, but a greater tendency to pool blood in the legs
than was observed in the pilot.

CONCLUSIONS
On the basis of the preflight and postflight data, it must be

concluded that the pulsatile cuffs were not effective in lessening

postflight orthostatic intolerance. This conclusion is based not on


the occurrence of syncope during the pilot's first tilt, but rather

on the higher heart rates observed during subsequent tilts, as compared

with the control subject. It is well established that syncope in

itself is a poor indicator of the extent or degree of cardiovascular


deconditioning.

The pulsatile cuffs appeared to be effective in lessening the

degree o f postflight pooling of blood in the lower extremities as


judged by the strain gage technique.

i
REFERENCES

1. VOGT, F. B.: Effect of Esrtremity Cuff-Tourniquets on Tilt-Table


Tolerance After Water Imersion. Aerospace Medicine, vol. 36,
May 1965, PP. 442-4.4.6-
2. D I ~ E I W ,L, F.; AND JUDY, W. V.: Experiment M-1, Cardiovascular
Conditioning. Manned Space-Flight Ekperiments Interim Report,
Gemini V Mission, Washington, D. C., January 1966.

14
F- wJo.END

Six-hnwr water 5mmrsion studies, first subject.

Six-hour water immersion studies, second subject.


Six-hour w a t e r bunersion studies, third subject.
Sa-hour w a t e r immersion studies, fourth subject.
Cardiovascular reflex conditionin& system.
Cardiovascular eonditionZng pnewastic cuffs.
Schematic diagraaa of cardiovascular reflex conditioner..
Summasy of pulse rate during tilt-table studies of
@ s i n i V fljght crew.

Fa*39-9 SMaaary of blood pressure during t i l t - t a b l e studies

for Gemini V P U g h t crew.


Fig- 39-10 Pulse-rate change after Gemini missions compared w i t h
bed-rest data.

F&* 39-11 Data from first t i l t - t a b l e study of Gemini VI1 command

pilot
Pig- 39-12 Data from second t i l t - t a b l e study of Gemini VI1 camrmand
pilot .
Fig. 39-13 Data from t h i r d tilt-table study of Gemini V I 1 conapland
pilot
Fig. 39-14 Data from fourth eilt-table- study of G e m i n i VI1 coxinand

pilot .
Data fmn f*st t i l t - t a b l e study of Ejemini VI1 pilot.

Data from second tilt-table study of Qemlni V I 1 pilot.

gig. 39-17 Data from t h i r d tilt-table study of Gemini VI1,pilot.


Fig. 39-18 Data from fourth tilt-table study of &zmininf p-t.
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i
Medica Experiment MOO3

Lawrence F. Dietlein, MIDI


Chief, BionWicaJ, Reseazch Office
NASA Manned Spacecraft Center
Houston, !Texas
R i t a M. Rapp
Biomedicsl Research Office
NASA Manned Spacecraft Center
Houston, Texas
EXFERIMENT M-3, INFLIGHT EZRCISE - WORK TOLERANCE
by
Lawrence F. Dietlein, M.D.
Chief, Biomedical Research Office
NASA Manned Spacecraft Center
and
R i t a M. Rapp
Biomedical Research Office
NASA Manned Spacecraft Center

SUMMARY
The response of the cardiovascular system t o a quantified workload i s an
index of the general physical condition of an individual. U t i l i z i n g mild
exercise a s a provocative stimulus, no s i g n i f i c a n t decrement i n the
physical condition of eikher of the Gemini V I 1 crewmembers was apparent.
The r a t e of r e t u r n of t h e pulse r a t e t o preexercise l e v e l s , following
i n f l i g h t exercise periods, was e s s e n t i a l l y the same as t h a t observed
during p r e f l i g h t baseline studies.

OBJECTIVE
The objective of Experiment M-3 was the day-to-day evaluation of the
general physical condition of t h e f l i g h t crew with inc5easing time under
space f l i g h t conditions. The b a s i s of t h i s evaluation w a s the response of
the cardiovascular system (pulse r a t e ) t o a calibrated workload.

EQUIPMENT
The exercise device ( f i g s . 1 and 2) consisted of a p a i r of rubber bungee
cords attached t o a nylon handle a t one end and t o a nylon f o o t s t r a p a t
the other. A s t a i n l e s s - s t e e l stop cable limited the s t r e t c h length of
the rubber bungee cords and fixed t h e i s o t o n i c workload of each p u l l .
The device could be u t i l i z e d t o exercise t h e lower extremities by holding
the f e e t s t a t i o n a r y and p u l l i n g on the handle. Flight bioinstrumentation
( f i g . 3) was u t i l i z e d t o obtain pulse rate, blood pressure, and r e s p i r a t i o n
rate. These data were recorded on the onboard bfomedicalmagnetic tape
recorder and simultaneously telemetered t o t h e ground monitoring s t a t i o n s
f o r real- time evaluation.

37
PROOW
The device used i n Gemini VI1 required 70 pounds of force t o s t r e t c h the
rubber bungee cords maximally through an excursion of 12 inches. Exercise
periods(crew s t a t u s reports) were scheduled twice d a i l y f o r each crew-
member. Additional isometric-isotonic exercises were performed by each
astronaut approximately three times d a i l y . Blood pressure measurements
were obtained before and a f t e r each exercise period (crew s t a t u s r e p o r t ) .

i?ESULTS
The f l i g h t crew performed the exercises as scheduled. Heart r a t e s were
determined by counting 15-second periods f o r 2 minutes before and f o l -
lowing exercise, as well as the f i r s t and l a s t 15-second periods during
each exercise. Comparison of 1-g p r e f l i g h t exercise periods with suc-
ceeding periods a l s o revealed l i t t l e difference i n heart-rate response.
Inf l i g h t responses t o exercise are graphically i l l u s t r a t e d i n f i g u r e 4.
Heart r a t e s are plotted f o r the command p i l o t and p i l o t before, during,
and following exercise. Both astronauts exhibited a moderate r i s e i n
pulse r a t e during exercise, with a rapid return t o near preexercise levels
within 1 minute following exercise. Similar M-3 r e s u l t s have been
previously reported f o r the Gemini I V and Gemini V crews ( r e f s . 1 and 2 ) .

Representative preexercise and postexercise blood pressures are i l l u s t r a t e d


i n figures 5 and 6 f o r the command p i l o t . The s y s t o l i c values tended t o
be s l i g h t l y higher following exercise. Diastolic values were more variable,
but generally tended t o be s l i g h t l y higher following exercise. Samples
of telemetered physiological data obtained during a t y p i c a l i n f l i g h t
exercise are i l l u s t r a t e d i n figure 7.

CONCLUSIONS
The M-3 experiment on Gemini VI1 was successfully performed. On the basis
of the data obtained during t h i s mission, the following conclusions appear
warranted :
(1) The response of the cardiovascular system t o a calibrated
workload i s r e l a t i v e l y constant f o r a g individual during space f l i g h t s
l a s t i n g 14 days.
(2) The crewmembers a r e able t o per mild- to-moderate amounts of
work under t h e conditions of space f l i g h t hin the confines of t h e
Gemini spacecraft. This a b i l i t y continue i a l l y unchanged f o r
missions up t o 14 days.
(3) Using a variant of the Harvard Step Test as
decrement i n the physical condition o f the crew was apparent during the
14-day missions, a t l e a s t under the s t r e s s of the r e l a t i v e l y mild work-
loads imposed i n t h i s experiment.

RJ3FERENCES
1. Dietlein, L.F.: Experiment M-3, I n f l i g h t Exerciser on Gemini I V .
Manned Space F l i g h t Experiments Symposium, Gemini Missions I11 and
I V , Washington, D . C . , October 1965.
2. Dietlein, L.F. ; and Rapp, R.M.: Experiment M-3, I n f l i g h t Exerciser.
Manned Space-Flight Experiments Interim Report, Gemini V Mission,
Washington, D .C ., January 1966.

39
Pig. 1 Inflight exerciser maJor components.
Fig. 2 Inflight exerciser in use.
Fig* 3 Biomedical and co31.pmaulicationsharness used during
Gemini m mission.
Fig. 4 Inflight responses to exercise.
Pier* 5 Blood pressure of Gemini V I 1 command pilot from

lift-off through 192 hours ground elapsed time.


Fig. 6 Blood pressure of Gemini VI1 command pilot f r o m 192
through 322 hours ground elapsed time.

FQ. 7 Sample of telemetered physiological data during inflight


exercise. .
(Recorder speed, 25 mm/sec )
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Medical Experiment MOO4
II?FLIGHT PEONOCARDIOGRAM

Principal Investigators:
6. Vallbona, M.D.
'Baylor University College of Nedicine
Texas Institute for RehabiJdtation and Research
Houston, Texas
L. F. Dietlein, M.D.
Chief, Biomedical Research Office
NASA M a n n e d Spacecraft Center
Houston, Texas
MEASUREMENTS OF THE DURATION OF THE CARDIAC CYCIi3 AND ITS PHASES
IN THE GEMINI ORBITAL FLIGHTS - e

By C. Vallbona, M.D. and


* - .
L.F. Dietlein, M.D. ._

Baylor University College of Medicine

Texas Institute f o r Rehabilitation and Research I

1
and

NASA Manned Spacecraft Center

SUMMAXY
Simultaneous electrocardiographic and phonocardiographic records

were obtained on both crew members during the flight of Gemini IV and

Gemini V and on the Pilot of Gemini VII. Analysis of the data recorded

during flight revealed: 1) wide fluctuations of the duration of the cardiac


cycle within physiological limits throughout the mission; 2) fluctuations

in the duration of the electromechanical systole that correlated with the


changes in heart rate; 3) stable values for the electromechanical delay;

4) higher values for duration of systole and electromechanical delay in


the Command Pilot of Gemini V suggesting cholinergic influences; and 5) evi-
dence of adrenergic response at lift-off, at reentry, and for the few hours
preceding reentry. This adrenergic response was observed in all astronauts
"-

participating in this experiment.

OBJECTIVE
The objective of Experiment M-4 was to measure the duration of the
various electrical and mechanical phases of the cardiac cycle of astronauts
during orbital flight in order to gain information relative to the

functional cardiac status of flight crew members during prolonged space

missions.

EQUIPMENT
The experimental equipment system consisted of: a) a phono-

cardiographic transducer, b) an electrocardiographic signal conditioner

(preamplifier and amplifier), and e) an on-board biomedical magnetic tape

recorder.
The transducer and signal conditioners were housed within the

Gemini pressure suit, as reported previously (1). The sensor for the
heart sounds was applied parasternally in the left fourth intercostal space
of each subject, and remained attached to the chest throughout the mission.

Electrodes for the detection of the ECG signals were applied in the usual
location for the MX (manubrium-xiphoid) lead. The phonocardiographic
transducer used to detect the chest vibrations produced by each heart beat,

consisted of a 7 mm. piezoelectric microphone, 1 inch in diameter and 0.2


inches in thickness. It was developed by the Bioinstrumentation Section

of the Crew Systems Division. A 10-inch shielded cable connected the heart
sounds transducer to the signal conditioner housed in a pocket of the

astronaut's undergarment. The phonocardiographic signal was then conducted

from the signal conditioner output to the suit bioplug and thence to the

biomedical recorder.
The electrocardiogram and phonocardiogram were recorded simultaneously

throughout the flights of Gemini IV and Gemini V. They were recorded inter-
mittently in the Pilot of the flight of Gemini VII. The recording procedure
was entirely passive and did not require active participation on the part
of the flight crew members.
50
ANALYSIS OF DATA

The analog data registered on the magnetic tapes were played

back i n r e a l time a f t e r completion of the mission. The records were

semiautomatically d i g i t i z e d with a Telecordex analog-to-digital converter.

D i g i t a l readings were taken a t each one of the following points: a) a t

the onset of the $pS complex o r the beginning of the e l e c t r i c a l systole,

b ) a t the onset of the f i r s t h e a r t sound, c ) a t the onset of the second

heart sound which indicates the end of the mechanical systole and the

beginning o f d i a s t o l e , and d ) a t the onset of the next QriS complex which

indicates the end of the cardiac cycle (Fig. 1). A computer program
permitted the calculation of the duration of systole and diastole, the

i n t e r v a l between the onset of &RS and the f i r s t h e a r t sound (electro-

mechanical delay), and the i n t e r v a l between the f i r s t and second h e a r t

sounds. The same program computed the means and standard deviations of these

variables a f t e r each 15 consecutive beats (Fig. 2 ) . The regression equation

proposed by Hegglin and Holzmann was used t o predict the duration of systole

f o r a given h e a r t r a t e ( 2 ) .

Data were obtained during the following periods: a ) continuously

s t a r t i n g a few minutes before l i f t - o f f u n t i l the spacecraft had s t a b i l i z e d

i n orbit, b) continuously from 5 minutes before reentry u n t i l s-plashdown,


and c ) continuously f o r 1 minute a t hourly i n t e r v a l s f o r the f i r s t 24 hours

of the mission and a t 4-hour i n t e r v a l s f o r the remainder of the fliat

u n t i l 5 ininutes before reentry.

Data on the P i l o t of Gemini V I 1 were obtained: a ) continuously

from 15 minutes before l i f t - o f f t o 11 minutes i n t o the mission, b ) continuously

f o r 1 minute a t 1, 3, and 4 hours, and e ) continuously f o r 1 minute a t


hourly i n t e r v a l s during the periods assigned f o r r e s t (night, Cape Kennedy

time) from the 5th day through the 14th day of the mission. Limitations

i n the number of measurements i n the P i l o t of Gemini VI1 were imposed by

the 100-hour recording c a p a b i l i t y of the biomedical tape recorder. No

a recordings were made during reentry.


i
i RESULTS AND DISCUSSION
i Similar p a t t e r n s of change were observed throughout the missions,

although there were quantitative differences among the individual astronauts.

Figure 3 indicates the s e r i a l changes i n the duration of the

t o t a l cardiac cycle ( l i n e R ) , electromechanical systole ( l i n e S ) , the

electromechanical delay { l i n e T ) , and the time i'nterval between the f i r s t

and the second h e a r t sounds ( l i n e X ) of the P i l o t during the f l i g h t of

Gemini V. The p a t t e r n of changes presented here i s similar t o the p a t t e r n s

observed i n a l l the astronauts who p a r t i c i p a t e d i n t h i s experiment,

There i s usually a marked acceleration of the h e a r t a t the time of

lift-off. 'This i s r e f l e c t e d i n a very s h o r t cardiac cycle accompanied by

a proportional shortening of Systole and the period of electromechanical

delay e

There i s a gradual deceleration following i n s e r t i o n i n t o o r b i t ,

but a steady s t a t e i s not reached u n t i l approximately 16 hours from the

onset of the mission. Throughout the mission the duration of the cardiac

cycle varies considerably with concomitant changes i n the duration of

electromechanical s y s t o l e and of the time i n t e r v a l between the f i r s t and

second h e a r t sounds. The eZeetromechanical delay remains r e l a t i v e l y constant,

b u t usually there i s a s i g n i f i c a n t "anticipatory" shortening t h a t begins


$
i
everalhours before reentry. I n the instance of the P i l o t of Gemini V,

t h i s phenomenon began 20 hours before reentry. Low values f o r the duration

of the cardiac cycle and f o r i t s various components are always observed a t

reentry &en peak h e a r t r a t e s of about 160 beats per minute are not uncommon.
I
Electromechanical systole and the electromechanical delay reach t h e i r lowest
!

values a t t h i s time.

An interpretation of the significance of these findings requires the

establishment o f a functional relationship among the measured variables: the

duration o f electromechanical systole, of the electromechanical delay, and

the t o t a l duration of the cardiac cycle. Figure 4 illustrates t h i s relation-

ship. The average values f o r the duration of the cardiac cycle corresponding

t o 15 h e a r t beats a t d i f f e r e n t periods of recording are plotted on the ordinate.

" h e corresponding average values f o r electromechanical systole ( S ) , f o r the

electromechanical delay ( T ) , and f o r the time i n t e r v a l between the f i r s t and

the second h e a r t sounds (X) a r e p l o t t e d along the abscissa. It i s clear t h a t

the values of S, X, and T are longer &en the t o t a l duration of the cardiac

cycle i s also longer ( t h a t i s , when the heart r a t e i s slower). The normal

relationship i s shown i n the regression l i n e s ,

In the case of the P i l o t of Gemini V, these relationships were normal

i n p r a c t i c a l l y a11 instances, although lower-than-predicted values f o r systole

were recorded a t the time of reentry. I n the case of the Command P i l o t of

Gemini I V and t o a l e s s e r extent i n the P i l o t s of Gemini I V and V I I , observed

values were s l i g h t l y lower than normal (Figs. 5, 6, and 7). The P i l o t of

Gemini VTI exhibited a very prolonged cardiac cycle ( i . e . low heart r a t e )

during periods of r e s t , the highest values having been recorded during

mid-mission night sleep periods (instantaneous h e a r t r a t e s of 37 t o 45 beats

per minute) (Fig. 8).

53
It may be s t a t e d t h a t , i n general, shorter-than-predicted

measurements of cycle components f o r a cardiac cycle of given duration

are observed under the influence of adrenergic or s t r e s s f a c t o r s , whereas

longer-than-predicted measurements are indicative of the influence of

cholinergic or vagal factors. A preponderance of adrenergic influences

was thus uniformly noticed i n a l l the astronauts a t the time of l i f t - o f f

and especially a t the time of reentry.


A remarkable quantitative difference was observed i n the Command
. P i l o t of Gemini V (Fig. 9). I n t h i s individual the durations of electro-

mechanical systole and of electromechanical delay were s i g n i f i c a n t l y longer

than predicted f o r normal healthy subjects There was a r e l a t i v e shortening

of these periods only a t the time of l i f t - o f f and reentry. It may be assumed

t h a t the longer duration of systole and of electromechanical delay of the

Command P i l o t of Gemini V was an expression of increased vagal tone except

a t l i f t - o f f and reentry. Increased vagal tone was further suggested b y the

marked sinus arrhythmia recorded during sleep and quiet periods.

A prolongation of the electromechanical delay was reported by

Baevskii and Gazenko i n the f l i g h t of Cosmonaut Titov (3). An absolute

and r e l a t i v e prolongation of the mechanical systole was reported also i n the

f l i g h t s of Tereshkova and Bykovskii (4). It i s l i k e l y t h a t an increased

vagal tone accounted f o r these observations; however, since i n the case of

the Command P i l o t of Gemini V, manifestations of nausea or other untoward

symptoms of vagal preponderance d i d not occur, we may conclude

54
that the isolated finding of a prolonged electromechanical delay period
does not in an of itself have pathological significance.

ACKNOWTXDGEMENT
The authors acknowledge the assistance of Mr. W. Young, of
the Bioinstrumentation Section of the Crew Systems Division, MSC-NASA

and of Mr. T. 0. Townsend of the Texas Institute f o r Rehabilitation and


Research f o r their participation in the playback and digitization of

records, and of Mrs. S. Gotcher and Mrs. E. Stallworth f o r their assistance

in the preparation of the reports.

55
REFE3RENCES

1. Dietlein, L. F.: Manned Space Flight Experiment Symposium

Gemini Missions I11 and IV, Washington, D.C., October 18, 1965.
2. Hegglin, R. and Holzmann, M.: Ztschr. f. klin. Med. 132: 1, 1937.
3. Baevskii, R. M., and Gazenko, 0. G.: Kosmicheskie Issledovaniya:

2 (2): 307, 1964.


4. Baevskiil R. M. and Volkov, Yu. N.: Klinicheskaya Meditsina.

43: 6, 1-96?.

56
P

FIGURE

Fig. 1 Analog record of electrocardiogram and phonocardiogram

simultaneously registered. The duration of the cardiac cycle

and its various intervals can be derived from digitization of

these records at the indicated points.

Fig. 2 Sample of the computer output of beat-by-beat measurements of

the duration of the cardiac cycle and its phases and of averages

and standard deviations for 15 consecutive beats.

Fig. 3 Serial changes in the duration of the cardiac cycle (R), in

the duration of electromechanical systole (S), in the interval


between first and second heart sounds (X), and in the duration

of the electromechanical delay (T) in the Pilot of Gemini V.

Midnight, Cape Kennedy time, is indicated by arrows.

Fig. 4 Relationship between electromechanical systole (S), the time

interval between first and second heart sounds (X), the electro-

mechanical delay (T), and the duration of the cardiac cycle (R),

throughout the mission for the Pilot of Gemini V. Each plot,

represents average values for each period of recording.

Fig. 5 Relationship between electromechanical systole (S), the time

interval between first and second heart sounds (X), the electro-

mechanical delay (T), and the duration of the cardiac cycle (R),

throughout the mission for the Command Pilot of Gemini IT. Each
plot represents average values for each period of recording.

57
w
%.

r*
f

Relationship between electromechanical systole (S) , the time

i n t e r v a l between f i r s t and second heart sounds (X), the electro-

mechanical delay (T), and the duration of the cardiac cycle (R),

throughout the mission f o r the P i l o t of Gemini IV. Each p l o t

represents average values f o r each period of recording.

Fig. 7 Relationship between the electromechanical systole (S), the time

i n t e r v a l between f i r s t and second h e a r t sounds (X), the electro-

mechanical delay (T), and the duration of the cardiac cycle (R),

throughout the mission f o r the P i l o t of Gemini VII. Each p l o t

represents average values f o r each period of recording. The

values shown i n t h i s graph include those obtained a t l i f t - o f f but not

a t reentry. Most of the values were obtained during periods of

rest.

Fig. 8 S e r i a l changes i n the duration of the cardiac cycle (R), the

duration of electromechanical systole (S), the i n t e r v a l between

f i r s t and second h e a r t sounds (X), and the duration of the electro-

mechanical delay (T) i n the P i l o t of Gemini VII. Midnight (Cape

Kennedy time) i s indicated by arrows.

Fig. 9 Relationship between electromechanical systole (S) , the time

i n t e r v a l between f i r s t and second h e a r t sounds (X), the electro-

mechanical delay (T), and the duration of the cardiac cycle (R),

throughout the mission f o r the P i l o t of Gemini V. Each p l o t

represents average values f o r each period of recording.


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67
Medical Experiment M-5
t

i, B IOCHEM ICAL ANALYS I S OF BODY FLU I D S

I N MANNED SPACEFLIGHT

Principal Investigators

Harry S. Lipscomb, M.D.


Professor o f Physiology
Chairman, Department of Biochemistry
Baylor U n i v e r s i t y College o f Medicine
Texas Medical Center
Houston, Texas 77025

E l 1 l o t H a r r i s , Ph.D.
Head o f Biochemistry and Toxicology S e c t i o n
Manned Spacecraft Center
N a t i o n a l Aeronautics and Space A d m i n i s t r a t i o n
Houston, Texas 77058

Lawrence D i e t l e i n , M.D., Ph.D.


C h i e f , Biomedical Research O f f i c e
Manned Spacecraft Center
N a t i o n a l Aeronautics and Space A d m i n i s t r a t i o n
Houston, Texas 77058
MED ICAL EXPERIMENT M-5
BIOCHEMICAL ANALYSIS OF BODY FLUIDS

IN MANNED SPACEFL G HT e - .

It is the purpose of the M-5 experiment to determine the


metabolic cost of manned spaceflight by the analysis of bio-
logical fluids. Results of these biochemical analyses are
used as an indication of the physiological status of the
astronaut. Where changes are found to occur, efforts are made
to understand the mechanisms producing these changes and to
assess their significance relative to the spaceflight. The
measurements are thus divided into three parts. The first

part consists of pre-flight collection of urine samples and

whole blood from each crewman to establish baseline values for

the individual astronaut. The second portion of the measure-


ments assesses the physiological status of the crewmen as
reflected through analysis o f urine samples collected in-flight.
The final portion of these measurements utilizes urine and
blood samples collected immediately post-flight, and on two
subsequent occasions at 24 and 48 hours post-flight to estab-
lish the rate of return to baseline pre-flight values. Within

this context a series of biochemical determinations are per-

formed consisting essentially of fluid and electrolyte balance,


hormonal studies, and correlation o f the two.
I n t h e f i r s t p r o f i l e , water and e l e c t r o l y t e balance i s

r e l a t e d t o an examination o f t h e l o s s i n body we

occurs d u r i n g f l i g h t and an attempt a t c o r r e l a t i o n o f these

losses t o changes i n f l u i d d i s t r i b u t i o n and t h e compartments

o f t h e e l e c t r o l y t e space. T h i s i n v o l v e s measurement o f sodium,

potassium, and c h l o r i d e s , c a t i o n s and anions which serve a

c r i t i c a l r o l e i n r e g u l a t i o n o f membrane t r a n s p o r t . Total

plasma p r o t e i n concentrations measured b o t h p r e - and p o s t -

f l i g h t a r e used as an i n d i c a t o r , along w i t h blood volume and

hematocrit s t u d i e s , as an [ n d i c a t o r o f p o s s i b l e dehydration.

Water i n t a k e and u r i n e o u t p u t a r e measured t o determine whether

t h e p r i m a r y loss o f weight i s t h e r e s u l t o f i n s e n s i b l e loss

o r o f changes i n renal f u n c t i o n . To a i d i n an understanding

o f water and e l e c t r o l y t e balance and renal f u n c t i o n , the

hormone vasopressin ( t h e a n t i d i u r e t i c hormone from t h e p o s t e r -

i o r lobe o f t h e p i t u i t a r y ) and t h e adrenal m i n e r a l o c o r t i c o i d ,

aldosterone, a r e measured i n t h e u r i n e . The r e l e a s e o f t h e

p o s t e r i o r lobe hormone vasopressin is r e g u l a t e d by changes

b o t h i n t h e osmolar c o n c e n t r a t i o n of t h e blood p e r f u s i n g t h e

hypothalamus as w e l l as by changes i n pressure sensed by

c e n t e r s w i t h i n t h e l a r g e vessels o f t h e neck. It has been

p o s t u l a t e d t h a t , as i n recumbency, z e r o g r a v i t y should p r o -

duce an increase i n t h e t h o r a c i c b l o o d volume. T h i s increase

i n t h o r a c i c blood volume r e f l e c t e d by increased pressure i n

70
- 1- -
- _-- .-/------

t h e c a r o t i d a r t e r y baroreceptors i n t h e neck would l e a d t o

a r e f l e x decrease i n t h e s e c r e t i o n o f a n t i d i u r e t i c hormones,

r e s u l t i n g i n an increased u r i n e o u t p u t d u r i n g f l i g h t . Re-

lease o f t h e hormone a l d o s t e r o n e from t h e adrenal c o r t e x i s


\

a l s o p o s t u r e - and perhaps pressure-sens it i v e . Aldosterone

s t i m u l a t e s t h e r e n a l t u b u l a r r e a b s o r p t i o n o f sodium
’-?=% \

passu, water. I t s release i s decreased i n recumbency and

increased by an e r e c t p o s i t i o n . It i s p o s t u l a t e d t h a t , a s

i n recumbency, z e r o g r a v i t y would produce a decreased secre-

t i o n o f a l d o s t e r o n e w i t h diminished sodium r e a b s o r p t i o n and

an increased u r i n a r y output. I t can thus be seen t h a t t h e

s e c r e t i o n o f vasopressin and a l d o s t e r o n e is p o s t u l a t e d t o be

decreased d u r i n g b o t h t h e recumbent and t h e z e r o g r a v i t y

conditions. The n e t e f f e c t o f these should be a s t r i k i n g i n -

crease i n u r i n a r y output. These r e l a t i o n s h i p s a r e d e p i c t e d

i n Figure 1. l m p l i c i t i n t h i s study, t h e r e f o r e , is t h e neces-

s i t y f o r a b s o l u t e l y c o r r e c t measurement o f t o t a l u r i n e o u t p u t ,

b o t h p r e - and p o s t - f l i g h t , as w e l l as d u r i n g t h e s p a c e f l i g h t

proper. Since t h e volume o f u r i n e v a r i e s w i d e l y throughout

t h e 24-hour p e r i o d s , and because t h e osmolar concentra i o n o f

dissolved solutes i n t h i s u r i n e a l s o v a r i e s widely, it i s clear

t h a t s i n g l e u r i n e samples c o l l e c t e d d u r i n g f l i g h t a r e nsuffi-

c i e n t f o r an assessment o f p h y s i o l o g i c a l f u n c t i o n . It i s f o r
t h i s reason, i n f a c t , t h a t t h e u r i n e c o l l e c t i o n device has

been employed i n f l i g h t s t o t h e most e f f e c t i v e advantage o f

a l l o w i n g us t o secure t o t a l u r i n e outputs, as w e l l as a l i q u o t

t h e v a r i o u s u r i n e c o l l e c t i o n p e r i o d s and o b t a i n some idea o f

f l u c t u a t i o n i n t h e o u t p u t o f b o t h f l u i d and s o l u t e .

The second p r o f i l e i n v o l v e s t h e e s t i m a t i o n o f t h e p h y s i -

o l o g i c a l c o s t o f m a i n t a i n i n g a g i v e n l e v e l o f performance

during spaceflight. T h i s c o u l d be considered a measure o f t h e

e f f e c t s of stress during f l i g h t . To t h i s end, two groups o f

hormones a r e assayed. The f i r s t , 17-hydroxycorticosteroids

(17-OH-CS), t h e s t r e s s hormones from t h e adrenal c o r t e x , p r o -

v i d e a measure o f long-term s t r e s s responses. The second group

o f hormones, g e n e r i c a l l y c a l l e d catecholamines, i s represented

by t h e substances epinephrine o r norepinephrine ( a d r e n a l i n o r

nor-adrenal i n ) , which a r e secreted i n response t o immediate

s h o r t - t e r m emergency s i t u a t i o n s . Assessment o f 17-hydroxycorti-

c o s t e r o i d s and catecholamines p r o v i d e s us w i t h an o b j e c t i v e evalu-

a t i o n o f b o t h t h e s h o r t - and long-term stresses o f manned

spaceflight. I n 1912, Cannon f i r s t described t h e " f i g h t o r

f l i g h t " reaction t o stress. T h i s response, c h a r a c t e r i z e d by

increased h e a r t r a t e , increased c a r d i a c output, increased

c o a g u l a b i l i t y of t h e blood, e l e v a t i o n o f b l o o d sugar, and

d i l a t a t i o n o f t h e p u p i l s , prepares one f o r an immediate p r o -


tection from danger. The development of more accurate methods
for determining plasma and urinary levels o f catecholamines
has furnished one of the most important biochemical indicators
of the degree of this very rapid response to stress.
In the 1920's, Selye suggested that the glucocortico-
steroids, hormones of the adrenal cortex, and especially the
17-hydroxycorticosteroids, were important in the stress res-

ponse. More recent work has suggested that an increase in


17-hydroxycorticosteroids is seldom as sensitive an indicator
of stress as the increase in catecholamines. These relation-
ships are depicted in Figure 2. This figure presents a dia-
gramatic representation of the factors involved in the maint-
enance of plasma volume and fluid and electrolyte balance
which may help in the assessment of the stress involved in
spaceflight: Both aldosterone and antidiuretic hormone are
important in the regulation of plasma volume, and 17-hydroxy-
corticosteroids are also thought to play a significant role.
Figure 3 reflects the measurement o f urinary 17-hydroxy-
corticosteroids by the crew personnel of GT-7 in the pre-
and post-flight periods. The anticipated finding, which is
the striking rise in 17-hydroxycorticosteroids immediately

following re-entry, reflects essentially the stress o f the


re-entry procedure proper. We know that this i s a normal

73
response which t h e body manifests t o severe s t r e s s , and a

response, i n c i d e n t a l l y , which one needs f o r s u r v i v a l . An

i n t e r e s t i n g and unexpla ned f i n d i n g i n regard t o t h e 17-

hydroxycorticosteroids s t h e s t r i k i n g l y low l e v e l s sus-

tained during f l i g h t .

A s i n d i c a t o r s o f t h e s t a t e o f h y d r a t i o n and t h e e l e c t r o -

l y t e changes o c c u r r i n g i n t h e f l i g h t , u r i n a r y e x c r e t i o n o f

sodium, potassium, and c h l o r i d e was measured f o r t h e p r e -

f l i g h t , the in-flight, and t h e p o s t - f l i g h t p e r i o d .

U r i n a r y sodium e x c r e t i o n decreased s l i g h t l y d u r i n g

f l i g h t i n b o t h members o f t h e crew. immediately p o s t - f l i g h t

t h e r e was a r e t e n t i o n o f sodium so t h a t i t s e x c r e t i o n was

s h a r p l y diminished. Then a s h o r t time l a t e r t h e r e was a

marked r i s e i n u r i n a r y sodium l e v e l s as t h e r e t a i n e d sodium

was b e i n g excreted.

The u r i n a r y e x c r e t i o n o f c h l o r i d e was found t o p a r a l l e l

t h a t o f sodium, as expected, w i t h a s l i g h t decrease d u r i n g

f l i g h t , a marked decrease d u r i n g t h e f i r s t 24 hours a f t e r

being o u t o f t h e c r a f t , and then a r e t u r n t o p r e - f l i g h t levels.

The amount o f potassium excreted i n t h e u r i n e d u r i n g t h e

14-day i n - f l i g h t p e r i o d was s i g n i f i c a n t l y l e s s than t h e amount

excreted e i t h e r b e f o r e o r a f t e r t h e f l i g h t . These f i n d i n g s

were seen t o be s i m i l a r i n t h e two crew members.

74
Urinary aldosterone levels (Figure 3 , black dots) are

determined by a double isotope dilsition technique using both


paper and gas-1 iquid chromatography. The procedure is

technically difficult and involved. Recovery rates are


about 40 to 60 per cent, and the error of the method under

the best of circumstances approaches 20 per cent. This


having been said, the pre-flight aldosterone levels are

essentially normal in both crew personnel. The trend in

both crew members is toward increased aldosterone excreti n

during flight with a rapid return to normal in the post-

flight period. The period of elevated aldosterone excret on


correlates with the period of sodium retention.

Urinary excretion of the adrenal medullary hormones


(Figure 4) reflecting short-term stress (catecholamines)
shows several interesting aspects. in one crew member,
adrenal in (epinephrine) is rather stable throughout pre-,
in-, and post-flight periods. The other crew member showed

significant elevations both on launch and during re-entry.

Nor-adrenal in (norepinephrine) for this latter crew member

showed para1 le1 launch and re-entry elevations, while the


first crew member demonstrated a significant rise o f nor-
epinephrine only upon re-entry. One is reluctant to specu-
late upon the significance of these varues, since they
c o n s t i t u t e a v e r y l i m i t e d s e r i e s of observations. A much

needed study on c o r r e l a t i o n s o f degrees o f s t r e s s w i t h p e r -

formance i n t h e Gemini program remains t o be made.

We now b e l i e v e t h a t norepinephrine r e f l e c t s p h y s i c a l

s t r e s s , w h i l e epinephrine more a c c u r a t e l y r e f l e c t s t h e

degree o f emotional s t r e s s . Ground-based s t u d i e s a r e

underway a t t h i s t i m e t o assess t h e importance o f these

two hormones as p r e d i c t o r s o f human performance under

c o n d i t i o n s o f a v a r i e t y o f stresses. i n - f l i g h t studies

o f these hormones remain, however, as t h e most s e n s i t i v e

i n d i c a t o r s o f b o t h p h y s i c a l and emotional s t r e s s .

From t h e data shown here, t h e f o l l o w i n g conclusions

can be drawn:

1. There a r e s i g n i f i c a n t decreases i n f l u i d i n t a k e

and u r i n a r y o u t p u t d u r i n g f l i g h t .

2. There a r e marked decreases i n t h e u r i n a r y e x c r e t i o n

o f sodium, of c h l o r i d e , and o f potassium d u r i n g f l i g h t .

3. There i s an apparently s i g n i f i c a n t t r e n d toward

elevation of aldosterone during f l i g h t .

4. As c o u l d be expected, t h e r e a r e considerable increases

i n catecholamine e x c r e t i o n immediately upon r e - e n t r y .

5. There i s a s i g n i f i c a n t increase i n 17-hydroxycortico-

s t e r o i d s a t t h e t i m e o f re-entry.
At this time, no explanation can be offered for the low
levels of 17-hydroxycorticosteroids during the flight.

Q. What effect would the accuracy of the volume


determinations have on your confidence in the reliability
of the data?
A. If the urine collecting devices were not working
properly and the total volume collections were not correct,
the data certainly would not be reliable. In such a case,
one would expect erratic results. However, in this case,
the values for sodium, potassium, and chloride are so remark-
ably similar for the two men that we believe the variations
seen are valid observations.

Q. Is there anything from ground-based studies that

would enable us to predict how best to protect personnel


from metabolic problems?
A. One might predict that adequate hydration and
assurance of the intake of at least 15-20 grams of sodium
chloride a day might prevent some of the in-flight sodium
retention observed. On the other hand, the data on aldosterone

may reflect an "in-flight1' primary hyperaldosteronism, a


possible result of the weightless state. More studies are
needed, however, to confirm this observation.

77
RENAL BLOOD
Perfus!on O=wrnrnmg points
Pulsation
Pressure

ERECT
POSTURE

CK'I

b'l
A ACTH
STRESS

I 1- PLASMA
VOLUME
H2°
REABSORPTION I 1 -'
t NO'
REABSORPTION
PLASMA
- I TUBULES
OSMOLALITY
U

78
CIRCA01AN
SYNCHRONIZATION I

CORTISOL

1 PLASMA CORTISOL

CONCENTRATION
- CORTI SOL
DISTRIBUTION
VOLUME

79
80
NO4
1
A-
x-- IN FLIGHT

Fig.
4 81
. .
. , , I

MEDICAL EXPERIMENT M-6

REVIEW OF MEDICAL FINDINGS OF GEMINI VI1

AND RELATED MISSIONS- BONE DEMINERALIZATION

h u l i n e Beery Mack, Ph D. .
Principal Investigator

Paul A . L a c h a n c e , Ph .D.

George P. Vose, M.S.

Fred B. Vogt, M.D.


Ass oc ia te Investigators
REVIEW OF MEDICAL FINDINGS OF GEMINI VI1

AND RELATED MISSIONS- BONE DEMINERAL

Experiment M-6 of the s e r i e s of investigations on bone

demineralization was designed t o find the effect upon the

human s k e l e t a l system of prolonged weightlessness and i m -

mobilization associated with confinement for a period of days

in the Gemini spacecraft This investigation was conducted

both on the primary and backup crews of the 14-day Gemini

VI1 mission, using the same method of radiographic bone den-

sitometry as that employed in the Gemini IV and Gemini V


s t u d i e s . Radiographs were made preflight and postflight of

the left foot in lateral projection and of the left hand in

posterior-anterior projection of each astronaut (a) 1 0 days and

three days preflight and on the day of launch at Cape Kenne-

dy: (b) on the aircraft carrier U .S .S. Wasp immediately after

recovery and again 24 hours later; and (c) at the Manned

Spacecraft Center at 11 days and 47 days following recovery.

In the laboratories of the Texas Woman's University

Research Institute, sections of the bones of the foot and

hand were evaluated for changes in s k e l e t a l mineralization

by the method of radiographic bone densitometry as developed


by Mack and associates. Although the left foot, with the d i s -

tal ends of the leg bones, and the left hand, with the d i s t a l

parts of the a r m bones, are the only parts of the anatomy of

the astronauts which a r e radiographed, a thorough histologic

study of multiple sections of cadaver bones of these parts of

the body shows that they contain all major types of trabecular

and compact skeletal t i s s u e .

As a complement t o the space fliuht s k e l e t a l investi-

gations , ground-based bed r e s t studies have been conducted


a t the Texas Woman’s University for the past three- and one-

half y e a r s , in which the calcium provision in the diet was

varied from one bed r e s t to the next, so that this nutrient was

fed at levels of 300, 500, 700, 800, 1 , 0 0 0 , 1 , 5 0 0 , and

2 ,000 milligrams per day, respectively, during s e v e n 14-day

bed r e s t periods and 1 , 5 0 0 and 2,000 milligrams during two

30-day periods of recumbency.

The subjects in these bed r e s t studies have been kept

consistently horizontal, with all of their needs cared for by

trained m a l e orderlies, and with their food spoon fed by the

dietitians on the project. With the broad range of calcium

levels in the bed r e s t d i e t s , and with x-rays of t h e s e subjects

84
taken d a i l y , it has been possible t o compare bone density

findings of the astronauts with those of certain of the bed r e s t

s u b j e c t s who were on the same dietary calcium level for the

s a m e period of t i m e . Moreover, more extensive radiographs

a r e taken of the bed r e s t subjects than of the a s t r o n a u t s ,

with routine balance studies a l s o made on them, which in-

volve calcium, phosphorus, nitrogen, creatine c r e a t i n i n e ,


@

17-ketosteroids and 17-hydroxycorticosteroids . This gives a

b a s i s for making many judgments which aid i n the prediction

of astronaut findings.
METHODS

Densitometer Assembly

The instrumentation employed for the photometric eval-

uation of bone density from radiographs in t h e s e reported

s t u d i e s was a special analog computer consisting of a s e r i e s

of s u b a s s e m b l i e s , all designed t o operate together a s a com-

pletely integrated system. The b a s i c units of the overall

a s s e m b l y , the theoretical aspects of the technique, and the

history of the development of the method have been reported

in references 1 , 2 , 3 , and 4 . Certain applications of the use

of the bone densitometric method employed in this study have

been described in references 5 , 6 , 7 , 8 , 9 , and 1 0 .


Standard Radiographic Exposure Technique

Because different x-ray units were used at the three

locales, the radiographs employed for densitometric measure-

ments at different sites are standardized by three methods:

(a) by the use of a n aluminum alloy wedge exposed on the

f i l m adjacent t o the bone; (b) by the u s e of a roentgen meter

t o determine the calibrated kilovoltage which would produce

identical beam qualities in each of the three x-ray units; and

(c) by exposing at each testing site a specially prepared

phantom containing a standard quantity of a s h enclosed in a

tissue-simulating absorber, shaped like a n os calcis , t o de-

tect possible technique variations .


The x-ray machines a r e calibrated before each group of

exposures by means of Victoreen roentgen-meters , in order t o

relate kilovoltage t o x-ray transmittance in milliroentgens

through a standard 2-millimeter aluminum filter under a spe-

cific x-ray intensity. Under the exposure conditions utilized,

a l l units yield a beam quality of 60 kilovolts, comparable with

the central unit at the Texas Woman's University.

The x-ray f i l m used in this investigation was Eastman

Type AA f i l m , which was exposed in cardboard holders.

86
The term “x-ray absorbence” by bone as used i n this re-

port refers to the beam attenuation resulting from the hydroxy-

a p a t i t e and water-organic contents of bone in their relative

molecular weight concentrations, together with the over- and

underlying soft t i s s u e . The results are reported in terms of

wedge m a s s equivalency of the bone s i t e s evaluated. Although

changes in composition or thickness of the extra-bone tissue

could account for slight changes i n t o t a l x-ray absorption, our

tests have shown t h a t , in the c a s e of t h e os c a l c i s particular-

l y , errors accountable to changes in soft t i s s u e mass a r e in-

significant .
Anatomical sites for bone evaluation have been chosen

and conditions of exposure have been developed which would

maximize the x-ray image of the mineral components of bone.

Evaluation of Wedge Mass Equivalency

in the Bones Evaluated

As noted, radiographs were made preflight and postflight

of the left foot i n lateral a s p e c t , and of the left hand in pos-

terior-anterior projection of e a c h astronaut in the Gemini VI1

study. In the previous investigations of bone mass changes

before, during, and after orbital flight, which has involved


the Gemini N and the Gemini V astronauts , the same radio-

graphic exposures were made.

C e n t r a l QS calcis s e c t i o n . -The tracing path a c r o s s the

left os calcis runs diagonally between conspicuous posterior

and anterior landmarks which, by superimposing s u c c e s s i v e

radiographs, c a n be reproduced accurately in s e r i a l f i l m s of

the same individual. This single path ( 1 . 3 mm in width) is

known as the "Conventional s c a n . " See Figure 1. This is a

revealing site for measuring bone mineral changes , since this

penetrates a highly trabecular area of t h i s bone, surrounded

by a periphery of cortical bone. A cross-section radiograph

of a cadaver bone made at the s a m e place at which the "con-

ventional" s c a n is traced is shown in Figure 2 .

p a r a l l e L x c a l c i g a a l u a t i a . -Approximately

60 per cent of the total os calcis mass was evaluated in the

parallel path system. After making the conventional s c a n , a

s e r i e s of parallel paths 1. O millimeter apart from center of

s c a n t o center of s c a n were scanned beginning 1 millimeter

above the conventional path and continuing to the lowest

portion of the bone The total number of paths scanned there-

after is proportional t o the s i z e of the bone which, of c o u r s e ,


h a s individual variations. For the command pilot of Gemini

VI1 38 paths and for the pilot 42 paths were required to cover

the os calcis portion examined. Figure 3 illustrates the

alignment of parallel paths through the os calcis portion ex-

amined, although the paths d o not go entirely a c r o s s the bone

i n the illustration.

n e t a h . - A single scanning path was made through

the t a l u s of the left foot originating at t h e inferior surface

and projecting anteriorly to the conspicuous landmark shown

in Figure 1.

Sections pf the phalanx 4-2 and 5-2. -The second pha-

lanx of the fourth and the fifth finger of the left hand was

scanned by parallel c r o s s -sectional paths 1 millimeter apart

aligned tangentially with the longitudinal axis and covering

the entire bone a r e a .

T& C a R i t a t c . - A section the width of the scanning beam

was traced a c r o s s the wrist c a r p a l capitate on a diagonal line

from a point above the capitate-hamate joint on the l e f t t o a

point at t h e lower right, which avoids overlapping of the


scaphoid. See Figure 4 for a n illustration of the tracing

paths of hand phalanges 4-2 and 5-2, and of the c a p i t a t e .

RESULTS

Bone Mass Changes in Central Os C a l c i s Section

("Conventional" Path) of Gemini VI1 Astronauts

The x-ray absorption values (in terms of calibration

wedge equivalency) which were obtained from the central os

calcis section throughout the Gemini mission are reported in

Table I and are shown graphically in Figure 5. Based on a

comparison of the data obtained from the radiographs made

immediately before and immediately after launch, this central

or "conventional" segment of the os calcis exhibited very

minor changes during the flight, both for the command pilot

and the pilot.

The c e n t r a l os calcis data for the command pilot show

that the second and third radiographs made before the orbital
flight were c l o s e l y similar, and were somewhat higher than

the initial preflight v a l u e . The x-ray made immediately post-

flight was only slightly lower than that made immediately pre-

flight. The f i l m made the day following recovery was essen-

tially the s a m e i n bone m a s s as t h e last preflight f i l m , with


the last two radiographs showing higher bone m a s s values than

the preflight f i l m s .

The values for the pilot ran approximately in the s a m e

order as those of the command pilot. For both astronauts, the

x-ray made 11 days after the orbital flight was highest in cali-

bration m a s s equivalency of a n y radiograph of the s e r i e s . It

should be noted t h a t the astronauts were encouraged t o con-

sume foods high in calcium and phosphorus during this period.

Moreover, this fell in the Christmas holidays when extensive

food consumption was the order of the d a y .

Os Calcis Values of Back-up Crew

The back-up crew for Gemini VI1 consisted of Astronaut

Edward White and Astronaut Michael Collins. The spread

from the highest to the lowest x-ray absorbency value in the

central os calcis section of Astronaut White was 2 . 5 per

c e n t covering a period of three months and 10 d a y s . That of

Astronaut Collins was 3 . 2 per c e n t over the same period.

The back-up crew was ground based with limited dietary

records during the preflight but not during the postflight period.
Bone Mass Changes in Multiple Sections

of the Os C a l c i s

Table II shows that the changes i n the overall sum of

the s e c t i o n a l v a l u e s obtained from the parallel s c a n s made in

the radf command pilot on the carrier im-

diately recovery was only -2.49 per c e n t less

de immediately before launch. The comparable

change in values for pilot was -2 -63 per c e n t (Table

The tables show also that t h e greatest change during flight i n

multiple s e c t i o n s of the os calcis of

the command lot was -5.17 per c e n t , while that of the

pilot was -7 -66per c e n t . A graph of the sums of the cali-

bration wedge equivalency values for the multiple os calcis

sections for e a c h of the preflight and postflight radiographs

is shown for both astronauts in Figure 6 .

Although there are inconsistencies i n the magnitude of

changes from section t o section in the multiple scans of the

os c a l c i s , it is seen in Figure 2 that the trabecular t i s s u e

in the interior of the os calcis is irregular in design through-

out.

92
X-Ray Absorption Changes i n Section

of the Talus

Figure 7 shows t h a t , during the preflight the m a s s of

the section evaluated in the talus f i r s t increased and then de-

c r e a s e d for the command pilot, with a value at the time of

launch which was slightly higher than the initial preflight

level. The pilot showed a slight decrease in this site pre-

flight. Postflight, both astronauts exhibited a marked in-

crease for 11 d a y s , with f i n a l values not markedly different

from t h e initial levels. In general this represents t h e s a m e

pattern of change as t h a t shown by the "conventional" sec-

tion of t h e os calcis, although the bone mass losses were

slightly greater in the section of the t a l u s which was eval-

uated than in t h e os calcis. The calibration wedge m a s s

equiva'lency at the talus scanning site obtained from the

radiograph made immediately postflight was 7.06 per c e n t

lower than the f i n a l preflight value for the command pilot and
2

4 .OO per c e n t lower for the pilot. The t a l u s showed the

same directional changes postflight in bone m a s s as did the

os c a l c i s in the c e n t r a l , or "conventional" s e c t i o n .

93
Bone M a s s Changes in the Hand

Hand Phalanx 4-2. The method of positioning the hand

for exposure of a radiograph is shown in Figure 8 . As in the

case of the os calcis, multiple parallel s c a n s were made

a c r o s s hand phalanges 4-2 and 5-2 with distances of 1 mil-

limeter from the center of one s c a n t o that of the next s c a n .

In this manner, the entire area of e a c h phalanx was evalu-

ated in posterior-anterior projection.

From the t i m e of taking the radiograph made immedi-

ately before launch until that which was made 14 days l a t e r ,

immediately after recovery on the carrier, the command pilot

sustained a n overall change in the 25 s c a n s required t o cover

phalanx 4-2 of -6.53 per c e n t . The change in this anatomi-

c a l site for the pilot during the same period was -3.82 per

c e n t , with 25 s c a n s required to cover this bone.

Figure 9 c o n s i s t s of graphs of the calibration wedge

equivalency values for hand phalanges 4-2 for the s e r i a l

radiographs of the two Gemini VI1 astronauts. The graph of

the command pilot shows that the value for phalanx 4-2 was

higher at the beginning of the orbital flight than was the first

94
preflight value, with a decline by the close of the flight This

was followed by a gradual increase after the flight. The graph

for phalanx 4-2 of the pilot shows a marked increase in bone

m a s s during the first seven days of preflight, followed by a

decrease during the last four preflight days Following the de-

c r e a s e during the flight, there was a sharp and then a gradual

postflight increase .
Phalanx 5-2. Figure 1 0 includes a graph of the

calibration wedge mass equivalency data on hand phalanx 5-2

of both Gemini VI1 astronauts. The values for the command

pilot did not experience a s marked preflight and postflight

changes a s did those of the pilot.

From the beginning t o the c l o s e of the orbital flight,

the command pilot sustained a n overall change in the 18 par-

allel sections required to cover phalanx 5-2 amounting t o

-6.76 per c e n t . In the 17 s c a n s which covered hand phalanx

5-2 of the pilot, a n overall chaage in bone m a s s of -7.03 per

c e n t was iound.

m a t e . Between the x i a y made immediately before

the orbital flight and that made immediately after recovery on

95
the c a r r i e r , the change in m a s s of the section of the capitate

which was evaluated was -4.31 per c e n t for the command pilot

and -9.30 per c e n t for the pilot. (See Figure 11). As i n the

x-rays made in other anatomic sites, the astronauts both went

u p slightly between the first two f i l m s of the capitate series,

and then decreased in calibration wedge m a s s equivalency be-

tween the second and final preflight radiographs, Character-

i s t i c of all s i t e s evaluated, the capitate made a marked re-

covery of m a s s (in terms of x-ray absorbency) during the first

24 hours following the mission hi both astronauts. Then there

was a marked increase in m a s s of this bone during the next

1 0 d a y s , reaching the highest l e v e l a t this t i m e . Then the

bone m a s s decreased somewhat until the last radiograph was

taken 37 days after the orbital flight was over. The final

level of m a s s in this bone for both men, however, was higher

in the last radiograph than in the x-ray immediately before

the flight.

Work on Fine Structure Changes in Bone Tissue

from Radiographs

In all anatomical sites upon which measurements were

made on the astronauts of the Gemini VI1 mission, rapid gains


in bone m a s s were found during the f i r s t 1 2 hours in which the

command pilot and the pilot were ambulatory on the carrier.

(See Figures 5 , 6 , 7 , 9 , 1 0 , and 11) This s a m e bone mass

phenomenon h a s been found in astronauts during other mis-

s i o n s , and in bed r e s t subjects who have changed from bed

r e s t to a n ambulatory p h a s e , or from one extreme dietary level

of calcium t o another.

A means of verifying these rapid changes is being ex-

plored by studying fine structure patterns in bone by methods

previously used exclusively for photographic interpretations ,

with applications primarily made in reconnaissance s t u d i e s .


The first s t e p is being made in this direction by the Principal

Investigator in cooperation with Mr. Lyle D. C a h i l l , using

f a c i l i t i e s and techniques available at Data Corporation

(Dayton, Ohio), a company of which he is president. Some

of the x-ray f i l m s of Gemini V , a mission during which bone

m a s s changes were greater than in the Gemini VI1 mission,

have been used in this i n i t i a l x-ray fine structure study (11).

This constitutes the beginning of routine three-dimensional

tests on our x-rays t o locate fine structure pattern changes

in the bone s e c t i o n s evaluated.

97
Comparison of Bone Changes i n Astronauts

of the Gemini IV, V , and VI1 Missions

Bone mass l o s s e s in the crew of Gemini VI1 tended t o be

markedly lower in all anatomical sections which were evalu-

a t e d than in the astronauts of Gemini IV, and particularly than

those of Gemini V. This is shown clearly in Table 111, in

which the overall values for the various sites are outlined 8

and in Table N in which changes are given for all c r o s s -


sections of hand phalanx 5-2 for all six of the astronauts of

these three missions.

The summary on the following page gives the mean daily

calcium intakes and the os c a l c i s bone changes on the part of

the astronauts of the three missions under d i s c u s s i o n , and of

TWU bed r e s t subjects consuming a comparable quantity of

calcium for the same period of t i m e . The general relation-

ships between dietary intake and bone m a s s changes in the os

calcis are obvious from a n examination of the summary, both

for the astronauts and for the corresponding TWU bed r e s t

subjects. The most distinct differences are s e e n in a c o m -

parison of the results of the astronauts of Gemini V and Gem-

ini VII, the former having consumed about one-third as much

calcium during flight as the latter.


Calcium Intakg nsitv Chancre
(calibration wedge
(milligrams) e quiva len e y )
(srams 1
Command Pilot .......... 679 -7.80
Pilot .................. 739 -10.30

TWU Bed R e s t
Subject 1 ............ 675 -2.67
Subject 2 ............ 659 -4.25
Subject 3 ............ 636 -3.39
Subject 4 ............ 636 -3.59
Mean of Bed Rest
Subjects .......... 651 -3.47

GXWJUY
Command Pilot .......... 373 -15.10
Pilot .................. 333 -8.90

T W U Bed Rest
Subject 1............ 307 -8.65
Subject 2............ 292 -5.06
Subject 3............ 303 -7.89
Subject 4............ -3.06
Mean of Bed Rest
..........
Subjects 302 -7.41

Gl3!muu
Command Pilot .......... 945 -2.91
Pilot .................. 921 -2.84

TWU Bed R e s t
............ 931
........... . l .021
Subject 1 -3.46
Subject 2 -3.56
............l. 034
............l .020
Subject 3 -5.79
Subject 4 -5.11
Subject 5 ............ 930 -5.86
Mean of Bed Rest
Subjects .......... 987 -4.76

99
Figure 11 brings together the findings concerning the

"conventional" segment of the largest bone in the foot, the os

calcis , of the astronauts in Gemini IV, Gemini V , and Gemini

VI1 during flight, in comparison with the Texas Woman's Uni-

versity bed r e s t subjects on the s a m e level of dietary calcium

for a n equivalent period of time. The astronauts of Gemini VII,

who participated in the longest period of flight,experienced

far lower l o s s e s in the os calcis, as has been shown a b o v e ,

than were found in the crews of Gemini IV or V. The l o s s e s

were even lower than those in the TWU comparable bed rest

s u b j e c t s . For the crews of Gemini IV and Gemini V , the


l o s s e s in os calcis values were greater than occurred in the

bed r e s t s u b j e c t s .

The s a m e comparisons are shown in Figure 1 2 for hand

phalanx 5-2. In this case , however, notably greater de-

c r e a s e s in bone m a s s during flight were found for all astro-

nauts than for the TWU bed r e s t subjects who consumed

equivalent quantities of calcium for a time period equal t o

the t i m e of the respective f l i g h t s , This would indicate that

there is the need t o find whether or not exercise routines are


possible which would affect the bone m a s s in the hands and

fingers t o a greater degree.

Texas Woman's University 14-Day Bed R e s t Study

including Isometric and Isotonic Exercises as in

the Gemini VI1 Mission

In order to t e s t the possibility t h a t , a s i d e from the im-

portance of dietary calcium, the isometric and isotonic exer-

cise program practiced on a daily routine basis by Astronauts

Borman and Love11 during the Gemini-Titan VI1 mission could

have been one parameter which contributed to the lowered

bone m a s s loss by these a s t r o n a u t s , a 14-day bed r e s t pro-

gram was planned and carried out as one of the bed rest

units conducted at the Texas Woman's University.

Four men were equilibrated with respect to os calcis

bone m a s s and calcium balance, after which they took part in

a 14-day s u p i n e , horizontal bed r e s t unit without e x e r c i s e .

After this i n i t i a l 14-day bed r e s t unit, during which 8 00 mil-

ligrams of calcium were provided d a i l y , two of the same

men took part in a second bed r e s t , following an ambulatory

period of equilibration. Throughout all phases of this study

800 milligrams of calcium per day was provided, as in the

101
first bed rest. The second bed r e s t was conducted i n exactly

the same manner as the first I except for the f a c t that the e x -

e r c i s e program used in Gemini VI1 was followed.

Dietlein and Rapp (12) reported on the u s e of a n inflight

exercise instrument used in Gemini VII. The b a s i s of the

evaluation of the e x e r c i s e on Gemini VI1 was the response of

the cardiovascular system (pulse rate I blood pressure I and

respiration rate) t o a calibrated workload. The exercise de-

vice, used both on the Gemini VI1 astronauts and on the two

T W U bed r e s t s u b j e c t s consisted of a pair of rubber bungee


I

cords attached to a nylon handle at one end and t o a nylon

foot s t r a p a t the other.

The exercise program utilized in the Gemini VI1 and i n

the TWU bed r e s t programs were the s a m e I and were more

extensive than that described in the report cited in the above

paragraph. The program followed in the bed r e s t study is

described in more d e t a i l by Mack and a s s o c i a t e s (6). A

previous bed rest study described in Reference ( 8 ) shows the

s a m e trend in bone mass of the os c a l c i s in a ground based

study conducted cooperatively by the Texas Institute of


Rehabilitation and Research (Houston) and the Texas Woman's

University,

When the classical "t" test was applied t o a comparison

of the bone mass findings during the first bed r e s t without ex-

e r c i s e and the second bed r e s t with programmed e x e r c i s e ,

with the data for both men pooled, the bed r e s t unit with exer-

cise surpassed that without exercise in bone mass (in terms

of wedge m a s s equivalency) by a difference which was statis-

tically significant (P.(O. 05).

A comparison of the pooled data of both men on urinary

calcium excretion using the "t" test, showed that the amount

of calcium l o s t in the urine was greater when the bed rest

without exercise was in progress, than in the bed r e s t period.

The former surpassed the latter by a highly significant dif-

ference (P< 0.01).

Figure 13 c o n s i s t s of regression lines for the bone

mass pooled data of both men for the bed r e s t periods with

and without e x e r c i s e , drawn by a n IBM 1620 computer. The

only difference between the regression lines for the two bed
r e s t periods were the slopesl which were steeper for the bed

r e s t without e x e r c i s e . Figure 1 4 gives a graphic representa-

tion of the regression lines for the urinary calcium excretion

levels pooled for both men during the respective bed r e s t

periods, the first with no exercise and the second with a pro-

gram of isometric and isotonic e x e r c i s e .

SUMMARY

The level of food intake undoubtedly h a s been one of

the major parameters accountable for the difference in levels

of mineral l o s s by the astronauts. This has been supported

by the ground based bed r e s t studies of the Texas Woman’s

University s e r i e s . Another factor probably responsible at

least in part for the comparatively low l o s s e s in bone mass of

the largest bone of the foot by the astronauts of Gemini VI1

was the fact that they engaged in isotonic and isometric ex-

e r c i s e following a ne-designed program and using a n exer-

c i s e r developed by Dietlein and Rapp (1 2). This exercise

routine h a s been repeated in a TWU bed r e s t unit with highly

positive results ( 6 ) . In addition the Gemini-Titan VI1 astro-

nauts slept for longer periods of time than did those of

Gemini IV and Gemini V.


The findings of the bone l o s s e s in the various anatomical

sites discussed in the three Gemini missions of this report

show that time is not the chief factor responsible for s k e l e t a l

l o s s during space flight, but that some other factor or factors

play a part in t h e s e changes.

In c l o s i n g , it should be noted that the s k e l e t a l l o s s e s

experienced by the astronauts during t h e s e studies were re-

placed within short periods of t i m e following the close of the

respective flights. As examples, see Figures 6 , 7 , and 8 .


REFERENCES

1. Mack, Pauline Beery; George P. Vose; and James Donald


Nelson, New QeveloDments b E u u i ~ m e n for
t the Roent-
uenouraDhi(; Measurement of Bone Density, American
Journal of Roentgenology, Radium Therapy, and Nuclear
Medicine, Vol. 8 2 , p. 647 (1959)

2. Mack, Pauline Beery, RadiouraDhiG Bone Densitometry,


Conference under sponsorship of the National Aeronau-
tics and Space Administration and the National Insti-
tutes of Health, NASA SP-64, Washington, D.C , .
March 25-27, 1965 (Published 1966)

3. M a c k , Pauline Beery , Results from the Studv d B o n e nw-


& , & y h u A D m a i s a lQf Calcium S t a t u s , Papers Pre-
sented at the 1949 conference of the Milbank Memorial
Fund, November 16-17, 1949, Published by Milbank
Memorial Fund (Published 1950)

4. M a c k , Pauline Beery: Anne T . O'Brien; Janice M. Smith:


and Arthur W. Ejauman, A, Method for Estimatinq the De-
uree of. Mineralization of Bones from Tracinq of Roent-
w u r a m , Science, V o l . 8 9 , p . 467 (1939)

5 . Mack, Pauline Beery and Staff, Semiannual Reports to


the National Aeronautics and Space Administration,

Fourth Semiannual Report, March 31, 1965


Fifth Semiannual Report, September 3 0 , 1965
Sixth Semiannual Report, March 31, 1966

6 . Mack, Pauline Beery: Ralph E . Pyke; Effie Boggs Cream-


er: Betty Bohon Alford; Elsa Arciniegas Dozier: and
.
Fred B. Vogt , M .D , A Bed Rest Study with and without
Exercise Involvina 800 Millimams of Dietary Calcium
Daily, Seventh Semiannual Report to the National
Aeronautics and Space Administration, September 3 0 ,
1966

106
7. Mack, Pauline Beery: Roy E . Beauchene; Conrad L. Kinard,
M.D.; Helen Buck Campbell: George P. Vose; Albert L.
Kubala ,A- . . Studv Involvi n g iha Feledilasad smuzi
Juice &Q pe-School and Elementary School Children,
Bulletin Number 4 , Human Nutrition S e r i e s , Nelda Chil-
ders Stark Laboratory for Human Nutrition Research,
Texas Woman’s University (1958)

8 . V o g t , F. B.; P. B. Mack: W. G. Beasley; W. A. Spencer;


D. Cardus; and C . Valbonna, E f f e c t of Bedrest ~n
Various Parameter9 ef Phvs ioloaical Functions, Part Xu.
The Effect of Bedrest on Bone Mass and Calcium Balance,
Texas Institute of Rehabilitation and Research, Report
to the National Aeronautics and Space Administration
(April 1965)

9. Vose , George P. : Pauline Beery Mack; Sidney 0. Brown;


and Ammon B. Medlen , Badiouraphic Determination sf
the Rate of Bone Healinq, Radiology,, V o l . 76, p . 770
(1961)

10. Vose , George P., and Pauline Beery Mack, poentueno-


louic Assessment of Femoral Neck Density as Related
&QFracturinu , The American Journal of Roentgenology,
.
Radium Therapy and Nuclear Medicine , V s l LXXXIX, p .
1296 (1963)

11 . Cahill , Lyle D ., and Pauline Beery Mack, Mathemati-


gal Determination sf.padioaraphic Pattern Density
Chanaes i n the Os Galcis of the Command Pilot of
&mini V durina Orbital Fliaht (in publication)

.
1 2 . Dietlein, Lawrence F , and Rita M. Rapp, Ex= riment
M-3, h f l i a h t Exercise- Work Tolerance, Gemini Mid-
program Conference, National Aeronautics and Space
Administration, Manned Spacecraft Center, NASA SP-
1 2 1 (February 23-25, 1966)

10’7
TABLE I

BONE DENSITOMETRIC VALUES OBTAINED FROM SCANNING

THE CENTRAL SECTION OF THE OS CALCIS OF GEMINI-

TITAN VI1 ASTRONAUTS AT INTERVALS THROUGHOUT THE

PRE-FLIGHT , ORBITAL FLIGHT, AND POST-FLIGHT PERIODS

Calibration Wedge M a s s
E quiva lency
Date
Pilot

2.4061

2.3846

2.4693

2.3991

2.4145

I I I

6 12/29/65 2.3526 2,6428

7 2/3/66 2.3081 2.5171

108
, TABLE -II.-Comparison of Bone Changes During Flight in Total Os Cab& From Multiple Sections
of the Os Calcis of the Crewmen in the Gkdni VI1 M.ission

I Command pilot Pilot

Position of tracing
IIntegrator
counts from
densitometer
12/4165
Integrator
ounts from
ensitometer
12118/65
Percent
change
from
1214 to
Integrator
:ounts from
ensito meter
12/4/65
Integrator
ounts from
ensitometer
12/18/65
Percent
change
from
1214 to
(average) (average) 12/18/65 (average) (average) 12/18/65

l m m above-_-__-_-------- 12 136 11 652 -3.99 13 791 13 359 -3.13


_ ___
Conventional - - _
- -- -- - - 12 409 12 049 -2.91 13 719 13 329 -2.84
1 mm below- ___
- _ _ _ _ _ -_- - _ 11 468 11 124 -3. 00 12 592 12 239 -2.81
2 mm below- _ - _ _ _ _ _ _ _ _ - - - _11 229 10 836 -3.50 11 937 11 689 -2.08
3 mm below _ _ _ _ _ _ _ _ _ _ _ - _ - 10 _ 988 10 648 -3.09 11 838 11 550 -2.43
4 mm below- _ _ _ _ _ _ _ _ _ _ - - - 10 _ 956 10 628 -2.99 11 928 11 465 -3.88
5 mm below _ _ _ _ _ _ _ _ _ . . _ 10-726
_-- 10 418 -2.87 11 613 11 306 -2.64
6 mm below- _ _ _ _ _ _ _ _ _ _ - _ -10 _ 460 10 142 -3. 04 11 314 11 186 -1.13
7 mm below _ _ _ _ _ _ _ _ _ _ _ _ _ -10 _ 332 9 934 -3.85 11 214 11 013 -1.79
8 mm below _ _ _ _ _ _ _ _ _ _ _ _ _ - 10 _ 238 9 709 -5.17 11 122 10 898 -2.01
9 mm below- _ _ _ _ _ _ _ _ _ _ _ _ _ _ 9 978 9 597 -3.82 10 799 10 591 -1.93
10 mm below _ _ _ _ _ _ _ _ _ _ _ _ _9- 690 9 415 -2.84 10 630 10 275 -3.34
11 mm below _ _ _ - _ - - _---- -- 9 630 9 248 -3.97 10 394 10 046 -3.35
12 mm below _ _ _ _ _ _ _ _ _ _ - - - - 9 294 8 964 -3. 55 10 126 9 890 -2.33
__
13 mm below- - - - - - - - - - -_
14 mm below _ _ _ _ _ _ _ - _ - _ - - - 8 694
8 968 8 690
8 568
-3.10
-1.45
9 790
9 536
9 562
9 276
-2.33
-2.73
15 mm below _ _ _ _ _ _ _ _ _ - _ - - - 8 557 8 381 -2. 06 9 280 9 186 -1.01
16 mm below _ _ _ _ _ _ _ _ _ - - - - - 8 090 7 996 -1.53 9 056 8 866 -2.10
17 mm below _ _ - _ _ _ _- -_-_- _ 7 795 7 578 -2. 78 8 979 8 586 -4. 38
18 mm below _ _ - _ _ _ _---- ___ 7 570 7 451 -1.57 8 960 8 274 -7.66
19 mm below- _ _ _ _ _ _ _ _ _ _ - - - 7 470 7 328 --1. 90 8 222 7 892 -4. 01
20 mm below _ _ _ _ _ _ _ _ _ - - - - - 7 403 7 268 -1.82 7 452 7 432 70.27
21 nun below _ _ _ _ _ _ _ _ _ - _ - L - 7 295 7 20c -1. 18 7 331 7 290 -0.56
22 mm below _ _ _ _ _ _ _ _ _ _ - - - - 7 221 7 184 -0. 51 7 241 7 lea -1.01
23 mm b e , _~_ _~ _ _ _ _ _ _ _ - - - - 7 176 7 141 -0.49 6 893 6 989 +l. 39
24 mm below- _ _ _ _ _ _ _ _ _ _ _ - -7 192 7 13C -0.86 6 890 6 843 -0.68
25 mm below _ _ _ _ _ _ _ _ _ c - - _ - 7 172 7 102 -0. 96 6 843 6 702 -2.05
26 mm below _ _ _ _ _ - _ _-_- _ - - 7 097 7 002 -1.34 6 829 6 503 --4.77
27 mm bleow _ _ _ _ _ _ _ _ _ _ - - - -6 914 6 83E -1.10 6 645 6 400 -3.69
28 mm below _ _ _ _ _ _ _ _ _ _ - _ - 6- 845 6 74C -1.53 6 451 6 243 -3.23
29 mm below _ _ _ _ _ _ _ _ _ _ - _ - -6 801 6 684 -1. 72 6 312 6 18C -2. 09
30 mm below _ _ _ _ _ _ _ _ _ L - - - -
6 319 6 21( -1. 72 6 218 6 12E -1.45
31 mm below _ _ _ _ _ _ _ _ - _ - - - - 6 022 5 96: -0.95 6 090 5 91c -2.95
32 mm below _ _ _ _ _ _ _ - _ L - - - -
5 694 5 60t -1.51 6 033 5 74E -4.72
33 mm below _ _ _ - _ - _ _ _ - - _ - - 4 98C 4 965 -0.54 5 764 5 631 -2.30
34 mm below _ _ _ _ _ _ _ _ - - - _ - _ 4 44E 4 385 -1.48 5 769 5 54E -3.81
35 mm below 3 75c 3 76: -1. 97 5 452 5 31s -2.44
_
_ _ _ _ _ _ _ _ _ L - - - -

36 mm belos- _ _ _ _ _ _ -- - _ - - 2 89€ 2 81f -2. 76 5 391 5 08s -5.63


37 mm below- _ __----_r ---- x 1 X 4 804 4 614 -3.96
38 mm below- _ _ _ _ _ _ _ _ _ - _ - _ x 1 X 4 362 4 25: -2.51
39 mm below- _ _ _ _ _ _ _ . . _ - _ -3 _ I! x 3 714 3 63i -2.06
40 mm below _ _ _ _ _ _ _ _ _ - - _ - - s 1 X 3 07C 3 32: +8.22

Total _ _ _ _ _ _ _ _ _ _ - _ _311
- _91: 304 241 x 352 394 343 427 X
Mean change-------- s a -2.46 s -2.54
I I
0, w
03 03
N 0

-
I
I w
co 0
N W
cn 0

I
r
0
N
w
-
I I
co 03
03 03
U aJ

I I
w Po

0 A
0, Q)

-
I I
rp Po

0 cn
0 A
FIGURE LEGENDS

Fig. 1 Positive of lateral foot radiograph showing location of

t h e c e n t r a l section of the os c a l c i s ("conventional"

section) which is evaluated f o r bone density changes,

as w e l l as the location of t h e section of t h e t a l u s

which is scanned.

Fig. 2 Cross-section of o s calcis at t h e position at which t h e

"conventional" segment is scanned.

Fig. 3 Radiograph of positive of os c a l c i s showing location of

t h e multiple sections which are evaluated. These scans are

made e n t i r e l y across t h e bone, p a r a l l e l with the conventional

section. They are 1 m m wide from t h e center of one scan t o

the center of the next scan, and hence they cover all of t h e

60 per cent of this bone which is involved i n t h i s evaluation.


Fig. 4 Positive of hand radiograph i n posterior-anterior projection,

showing position of p a r a l l e l traces on phaanges 5-2 and

4-2. The edges of t h e scans slightly overlap each other

and aover t h e e n t i r e bone i n each case.

Fig. 5 Graph of t h e c a l i b r a t i o n wedge mass equivalency data on

t h e "conventional" os calcis section which =re evaluated

f o r the two Gemini-VI1 astronauts.

111-a
Fig. 6 Graph of the c a l i b r a t i o n wedge mass equivalency d a t a

on t h e multiple os c a l c i s sections which were evaluated

for the two Gemini V I 1 astronauts.

Fig. 7 Graph of t h e c a l i b r a t i o n wedge mass equivalency d a t a

on the section of the t a l u s which w a s evaluated f o r t h e

two Gemini V I 1 astronauts.

Fig. 8 Positioning a subject f o r a hand x-ray. The subject i s

shielded by m e a n s of vinyl p l a s t i c sheeting which is

impregnated with a lead compound.

Fig. 9 Graph of the c a l i b r a t i o n wedge mass equivalency d a t a on

hand phalanx 4-2 f o r the two Gemini-VI1 astronauts.

Fig. 10 Graph of the c a l i b r a t i o n wedge mass equivalency data on

hand phalanx 5-2 for the two G e m i n i - V I 1 astronauts.

Fig. 11 Graph of the c a l i b r a t i o n wedge equivalency d a t a on t h e

c a p i t a t e f o r t h e two Gemini-VI1 astronauts.

Fig. 12 Comparison of Per Cent Charges i n X-Ray Absorbency

(Calibration Wedge Mass Equivalency) i n the "ConventionaJ"

O s Calcis S i t e by t h e Command P i l o t , t h e P i l o t , and the

Mean of ?wu Bed Rest Subjects who Consumed Comparable Amoun-bs

of CrilciumPer Day for the Crews of Gemini Tv, V, and V I I .


Fig. 13 Comparison of Per cent change i n X-ray absorbency ( c a l i b r a t i o n

wedge mass equivalency) i n t h e hand phalanx 5-2 s i t e by t h e

ornmand P i l o t , the P i l o t , and the mean of TW bed rest


subjects who consumed comparable mounts of calcium per

111-b
day for the Crews of Gemini TV, V, and V I I .

Fig. 14 First order regression lines for bone mass (data for

two subjects pooled) during the first I&-day supine,


horizontal bed rest when no exercise was taken (lower

the second bed rest when isometric

d Gemini V I 1 exercises were followed


te: regression lines were drawn by

fg. 1 5 F i r s t order re ession lines f o r UT calcium excretion

(data for two subJects pooled) durf first lbday

bed rest when no exercise was taken (upper curve), and

during Lhe second bed rest when programmed GemSni VI1

exercises were followed. Note: regression lines

dram by an 1620 computer e

Ill-c
. . .

. . .._
.. . . - .._.

Fig. 2
-5
J
%

4
I
C A LI 8 R A T ION W EDG E EQUI VALE NCY

C
C A L I B R A T I O N W E D G E EQUIVALENCY
(Grams)
O N W E D G E E Q U VALENCY
(Grams)
- - -

121
CALIBRATION WEDGE E Q U I V A L E N C Y
- -
-
g-
(G rams)
0 -
'0
-
L f u 'f; b
'00 0 0 0
'ts
0 0
0
I w I I Q I I

122
CHANGE IN O S C A L C I S X-RAY A B S O R B E N C Y ( P E R CENT)

I 1

O N - I b uO
1 1
_ - - - -N N N N N G ,
1 1 1

m o N P cno, 0 N P o m 0
1 1 1 1 1 1 1 1

- . - - . . . . n I m u

f---Command
Pi1ot

-
-Pi1 ot
Mean Of Bed
Rest Subjects

Command

+Pilot

Mean O f Bed
f--
Rest Subj ects

Command
t-
Pilot

f-- Pilot

M ean O f B ed
f--
Rest Subjects
CHANGE I N HAND PHALANX 5-2 %RAY ABSORBENCY

I 1 1 1
-1 - 1- _1 -1 1 1 1
n,n,I\)1\1Ncr,
1 1 1 1
0 n, + m a l O N P mal O N P mal
. # . 1 1 . . 1 . . 1 1 1 1
0

f---Command
Pilot

- Mean Of Bed
Rest Subject:

&,Command
I

2 Pilot

+Pilo+

t--M e a n Of Bed
Rest Subjects

.c- Command
Pilot

+Pilot

Mecn Of Bed
f--
Rest Subject2

Fig. 13 124
' !

-?
2. I

TIME IN >AYS

Fig. 14.
EFCRETION OF URINARY CALCIUM
(M1 If I grams)

CJ
9
-c
v,

-
N'
. . . . . .
...............
e.
E.. ..
. . . . . . . . . . . .
- ........
: -
v, .. ..P.
. a ..............
... .........
"--..&-
~ ~

..__.___--.-n L -...--.
-
LJ I--
. . . . . -0
0
. . . .
........
-.--.-.--..-____L_
. . . . . .

_-.._
0
I_____.
L
.
....
. . . .
.
. . a ...... . .

F --E
. . a. . . . . . . . . . . . .
__ ___ Ll
0 - r-..

3.26
Medical Experiment M 7
CALCIUM AMD NITROGEN BALANCE

Principal Investigators

NAME: Dr, G. Donald Whedon


TITLE: Director of Mational Institute of Arthritis and
Metabolic Disease
LOCATION: National Institutes of Health, Bethesda, Maryland

NAME: Dr. Leo Lutwak


TITLE: Jamison Professor of Clinical Nutrition
Director, Clinical Wztrition Unit
LOCATION: Graduate School of Nutrition
Cornel1 University
Ithaca, New York

NAME: Dr. William Neuman


TITLE: Professor of Radiation Biology
LOCATION: University of Rochester
Rochester, New York
CALCIUM AND NITROGEN BALANCE

DR. LU'IWAK: The M-7 experiment, flown only on the Gemini 7

f l i g h t , w a s a &day attempt t o l e a r n about metabolic balances

i n space. Although t h e formal t i t l e describes t h i s as a calcium

balance study, the experiment involved more than measurements of

calcium alone. About 99 percent of t h e body calcium i s present

i n t h e skeleton, but t h e movement of calcium i n t o and out of t h e

body i s dependent upon t h e movement of other substances as w e l l .

Calcium i s present i n t h e bone primarily as calcium phosphate;

thus i f we are Interested i n calcium balance we must measure

phosphate balance as w e l l . Phosphate i s a l s o r e l a t e d t o protein

metabolism and therefore nitrogen balance must a l s o be evaluated.

Balance may be defined as t h e difference between what comes

i n and what goes out. If you l o s e more than you put i n , you are

i n negative balance. If you are retaining, then you are i n pos-

i t i v e balance. There are various f a c t o r s t h a t may influence bal-

ance of an element. "he sources of l o s s may be through t h e urine,

through the feces, and through t h e sweat. Other f a c t o r s can in-

fluence t h e loss of calcium, of phosphorous, and of nitrogen i n

t h e urine, feces, and sweat and therefore these were measured as

well. "he goal w a s t o evaluate t h e effect of t h e Gemini 7 f l i g h t

on t h e metabolic balances of several substances. Originally t h e

i n t e r e s t w a s i n t h e e f f e c t of weightlessness, but t h e Gemini 7 f l i g h t

included variables other than weightlessness. The first s l i d e


(Figure 1) has been borrowed from the Mid-bogram Review dis-

cussion by Dr. Berry.

In the space flight we were concerned with influences of

the full-pressure suit, confinement and restraint, an abnormal

atmosphere for breathing, abnormal cabin pressures at varfous

times, abnormal temperatures, varyfng g forces at different times,


weightlessness, vibration, a variable degree of dehydration, and

so forth, and one other factor which is not listed in the figure,

’ a variable degree of activity. The subjects were not in a com-


pletely inactive state; they performed programmed activity, in-

cluding Bungee cord exercises at regular intervals in addition

to scheduled isometric exercises. Thus we were trying to measure

the effects of a variable number of variables on certain param-

eters that were related to the overall body economy, in an at-


tempt to see what the effect of this space flight could be - to
use the word that has been used before - on the cost of perform-
ing space flight. Now may I have the next slide please?
{Figure 2)

To this end, we measured many substances in the samples.


There were collections of urine and of feces, as well as of sweat.

The volume of the urine was measured; we measured the specific


gravity, which gave us some indication of the concentration of

the urine. Although I am not going to go into great detail in the

time we have, I do want to mention in passing that the specific


gravity of the urine was definitely increased during the in-flight
phase, indicating some degree of concentration; t h i s correlates

w e l l w i t h t h e observation t h a t t h e urine volumes in-flight were

low. We measured t h e pH of the urine. Creatinine i n t h e u r i n e

was determined because t h i s is a breakdown product of endogenous

muscle metabolism whose excretion i s considered t o be r e l a t i v e l y

constant i n any given individual. Variations i n creatinine ex-

cretion of a s m a l l order of magnitude could be a t t r i b u t a b l e t o

changes i n kidney function, but large changes i n creatinine ex-

cretion would indicate some e r r o r s i n collection. This i s t h e

first t i m e so ambitious a project was undertaken, t h e determina-

t i o n of complete metabolic balances i n t h e f i e l d , where the

"field" w a s several hundred miles away, completely out of t h e

control of t h e investigators; as we w i l l see, t h e measurement of

constancy of creatinine excretion, therefore, was a r a t h e r c r i t i -

cal measurement f o r US.

We measured calcium i n the urine, feces, d i e t , and sweat, as

w e l l as magnesium, sodium, potassium, phosphate, sulphate, chlo-

ride, and nitrogen.

The o v e r a l l plan consisted of three phases: a pre-flight

control phase; t h e in-flight study, and a post-flight control. It

was obvious t h a t t h e interpretations would be very limited; there

were two subjects involved, and any two individuals i n t h i s room

could vary from each other by a considerable order of magnitude.

Therefore, by using t h e same individuals as t h e i r own controls,

we hoped t o a t least diminish t h i s degree of v a r i a b i l i t y . Each


individual w a s t o be Studied during; a control phase, pre-flight,

This involved four subjects, t h e crew and t h e back-up crew,

Thereafter t h e crew would be studied during f l i g h t , and hope-

f u l l y we would have a post-flight control phase, t o see what the

degree of recovery w a s from whatever changes we might see in-

flight,

May I have t h e next slide?

(Figure 3)

The v a l i d i t y of a balance study depends upon constancy of

d i e t a r y intake, with a t l e a s t as good a knowledge of t h e dietary

intake as possible, "he discussion today is r e a l l y going t o be

a c r i t i q u e of our investigation r a t h e r than a s e r i e s of firm

conclusions, because of many things we have learned about haw not

t o do such a study. One.of t h e problems encountered w a s that t h e

d i e t a r y intakes varied considerably during each phase, The stan-

dard deviations f o r t h e intakes of n u t r i e n t s during each of t h e

phases are not listed, but t h e means vary considerabw. W


e tried

t o provide a constant d i e t , but since the men were r e s t r i c t e d i n

t h e amount of t i m e they could spare f o r pre-flight indoctrination,

since they w e r e q u i t e busy with many other tasks, t h e study was

started before having achieved constant intake. Every b i t of col-

l e c t i o n and analyzed material has been used because calcium

changes are very slow - a t e n day balance study i s a bare minimum


for validity - as t h e t e n days of pre-flight study were based on

e s s e n t i a l l y t e n d i f f e r e n t diets f o r each man, Because of t h i s ,

t h e r e w a s a s i g n i f i c a n t v a r i a b i l i t y i n each of t h e intakes of each


of the elements we were studying, for each man as well as from
man to man. The pre-flight diet was calculated to be as close

88 possible to the calculations of the in-flight diet as pre-

pared by Dr. LaChanee of the Crew Systems Division.


However, appetites vary, and the men took second helpings
of various foods; thus there was a significant difference in the
intake of every single food element when the pre-flight phase

was compared with the in-flight phase. Post-flight dietary in-

takes were very similar to the pre-flight, but comparisons be-

tween the pre- and in- or in- and post- showed significant dif-

ferences for both men. These differences were in addition to

the d w to day variability for each man. Phis immediately casts

doubt on the validity of any of the conclusions that could be


drawn based on balance data because of extreme variability,

first of all within each phase, and secondly because of the


changes between phases by a whole order of magnitude, for in-

stance, in potassium (the pre-flight intake was 100 milliequiv-

alents per day and in-flight was less than 40 milliequivalents

per day). This is a serious error for this particular study.

M e y I have the next slide, please.

(Figure 4 )
This figure shows some of the degree of variability. The

graph expresses balances (without any orders of magnitude) for

the four men who were studied during the pre-flight phase of ten-

days duration, It can be seen that, generally, there is a


$ i m i l a r i t y of pattern. (Mean values are p l o t t e d t o show t h e '

v a r i a b i l i t y from man t o man). Generally, t h e r e w a s constancy i n

terms of intake, (Intake is p l o t t e d from t h e zero l i n e down;

excretions are then p l o t t e d from t h e intake l i n e up. This i s t h e

standard technique f o r p l o t t i n g balances ) . The sweat l o s s e s

were measurable f o r calcium, magnesium, sodium, potassium, and

nitrogen; no phosphate loss could be measured i n t h e sweat,

These sweat losses, incidentally, are r e l a t i v e l y i n s i g n i f i c a n t i n

terms of t h e o v e r a l l amount ingested a n d ' t h e o v e r a l l balance.

But there w a s considerable v a r i a b i l i t y from man t o man. The pur-

pose of t h i s f i g u r e i s a p l e a f o r more s t u d i e s before drawing

conclusions about balances because of t h e tremendous interindivid-

ual variability.

For t h e in-flight intake, i d e n t i c a l menus were packed for

both men. The foods were i n sealed meal-packs, labeled i n terms

of day and Meal A, B, o r C f o r days one through fourteen. However,

f o r reasons which we haven't learned as y e t , t h e meals were n o t

eaten i n sequence o r were not available t o be eaten i n sequence.

Both men ate t h e same menu from day t o day. W e received an in-

f l i g h t log which w e t r i e d t o use as our basis f o r calculation of

in-flight intake. The log indicated t h a t Meal 5A may have been

the first meal eaten, Meal ?A t h e second m e a l , and Meal 1OC the

third meal. I n addition, some of t h e meals t h a t were ingested in-

f l i g h t probably were not eaten completely a t t h e t i m e they were

logged. Portions t h a t were l e f t over were eaten at a l a t e r time.

133
Therefore, t h e only data I am going t o s h b me mean figures f o r

t h e t o t a l period.

VOICE: Were you able t o get a good enough record so t h a t you

knew i n general what they ate so t h a t you could go back and re-

construct t h e diet?

DR. LUTWAK: Well, we have a record. I don't know how good

t h e record is. e are assuming the record i s accurate.


W W e know

t h a t it probably is not wholely accurate. For instance, t h e re-

cord states t h a t Meal 9 A w a s eaten on Day ? and then was eaten

again on Day 11. Obviously, one of t h e 9A's must have been a dif-

ferent meal. Presumably t h e r e were logging e r r o r s which would oc-

cur under such strenuous conditions. W e were able t o a r r i v e a t

approximate values f o r t h e means f o r 1 4 days. We have mean values,

which are r e a l l y t h e only basis we have f o r arriving a t any con-

clusions. N e x t s l i d e , please.

(Figure 5 )

Our primary i n t e r e s t was i n calcium balance, and p a r t i c u l a r l y ,

urinary calcium excretion. The reason f o r t h i s derives from ground-

based studies of normal subjects. Such studies of immobilization,

o r i g i n a l l y carried out some 20 years ago by Dietrich, Whedon, and

Shorr at t h e Cornel1 Medical School, and similar studies t h a t have

been carried out i n many other places subsequently, have indicated

t h a t under conditions of complete bedrest, urinary calcium increased

i n some individuals. Therefore, t h e urinary calcium excretion might

be an indicator of changes i n bone metabolism and bone physiology.


If immobilization i n ground-based studies may be equated t o con-

d i t i o n s of zero gravity, t h e primary change one might e to

see would be an increase i n urinary calcium, This has two implica-

tions: (1) urinary calcium can be derived from e i t h e r d i e t a r y

calcium o r from skeletal calcium; i f urinary calcium increases

excessively, it must come from t h e skeleton and demineralization

of t h e skeleton would be expected. ( 2 ) an increased urinary cal-

cium i n some individuals predisposes t o kidney stones (which can

produce t h e most excruciating pain known t o man). So t h e r e are

two s i g n i f i c a n t reasons f o r looking a t t h i s question of calcium

metabolism.

When t h e values f o r urinary excretion of calcium i n - f l i g h t

were examined, these were extremely low, much lower than t h e urinary

calcium measured during t h e pre-flight and t h e post-flight phases

f o r both individuals. We then looked a t t h e c r e a t i n i n e excretion.

As you recall, c r e a t i n i n e is measured as an index of complete col-

l e c t i o n s ; the c r e a t i n i n e values s i m i l a r l y were q u i t e low i n compar-

ison w i t h pre- and post-flight phases. This suggested t o us t h a t

t h e r e were e r r o r s i n t h e c o l l e c t i o n system, Whether t h e e r r o r was

i n t h e tritium d i l u t i o n o r i n t h e urine transport system itself,

we are not i n a position t o say. However, t h e in-flight urinary

c r e a t i n i n e values were approximately two-thirds those of t h e pre-

and post-flight phases. Since there w a s no other evidence f o r

severe kidney damage (and it would require extremely severe kidney

damage t o produce t h i s much of a diminution i n urinary c r e a t i n i n e ) ,

135
we f e l t j u s t i f i e d i n correcting t h e data t o t h e pre- and post-

f l i g h t mean excretions of creatinine. Now t h i s immediately in-

troduces another e r r o r of about 15 - 20% i n our values f o r urinary


calcium excretion, However, we have corrected a l l in-flight uri-

nary excretions t o t h i s base of creatinine. A l l subsequent pre-

sentations t h a t show in-flight data are based on corrected uri-

nary excretions.

VOICE: Pre-flight or post-flight data?

DR. LUTWAK: W e used t h e mean of t h e pre- plus post-flight

creatinine excretions. There were 10 days of pre-flight and 4 days

post-flight collections. W e used t h e sum divided by 1 4 because

we didn't feel j u s t i f i e d i n dropping any of t h e values. "here w a s

one very high value post-flight i n one man; there was one very high

value pre-flight i n another man. There w a s no r e a l reason f o r

dropping e i t h e r of these. May I have t h e next s l i d e , please.

(Figure 6 )

What could w e have expected t o f i n d ? This figure i s taken

from a paper of Dietrich, Whedon and Shorr, showing t h e changes

t h a t were found w i t h complete bedrest for periods of several weeks

duration. Four individuals are shown i n t h i s s l i d e and there are

several points t o be made. Let's j u s t concentrate on the urinary

calcium excretions. There i s extreme interindividual v a r i a b i l i t y .

If our two astronauts were t h e lower two subjects shown, one would

not expect t o find any s i g n i f i c a n t changes i n urinary excretion of

calcium. If, however, our two astronauts resembled t h e subject i n


t h e upper portion of t h e figure, w e would expect t o find s i g n i f i c a n t

increases. Therefore, we began our analyses with no prejudice.

Whether o r not we found any change i n urinary calcium, it s t i l l

wouldn't prove an e f f e c t of Gemini 7 Flight on calcium excretion.

Another point i s t h a t calcium excretion usually rose, beginning

during t h e f i r s t week and approaching a maximum by the second

week. Plateau values weren't reached u n t i l a f t e r t h e t h i r d week.

e were concerned with a two-week f l i g h t i n t h e present study and


W

therefore we might o r might not expect t o f i n d a plateau. Still

another s i g n i f i c a n t observation i s t h a t urinary calcium changes

recover q u i t e rapidly after a c t i v i t y i s r e i n s t i t u t e d , but it takes

a t least two t o four weeks before baseline values a r e again achieved.


We had planned o n l y , a four day post-flight control. May I have t h e

next slide?

(Figure 7)
Now, these are t h e data f o r urinary excretion of calcium. The first

portion represents t h e cormnand p i l o t and the other t h e p i l o t . Two


points here again. One, t h e command p i l o t had a baseline urinary

excretion of calcium t h a t w a s much i n excess and s i g n i f i c a n t l y dif-

f e r e n t from t h e baseline excretion of t h e p i l o t . If we extrapolate

from the findings of t h e Cornel1 Medical School study of 20 years ago,

one might predict t h a t one man would show a change in-flight and t h e

other would not, because individuals w i t h lower excretions under

control conditions did not show s i g n i f i c a n t changes as a result of

137
immobilization. This i s e s s e n t i a l l y what w a s found i n t h e

Gemini V I 1 study. The dotted l i n e s represent one standard de-

v i a t i o n from t h e mean; t h e points are individual d a i l y values of

urinary calcium excretion. There w a s a s i g n i f i c a n t difference i n

excretion, using t h e moving average type of calculation, during

t h e second week, i n comparison with the f i r s t week; these r e s u l t s

are p a r a l l e l t o those of ground-based studies. I n both men in-

f l i g h t calcium excretion w a s elevated; i n t h e p i l o t it w a s s l i g h t -

l y elevated while i n t h e command p i l o t it w a s s i g n i f i c a n t l y eleva-

ted. Post-flight, both men showed elevated urinary excretions of

calcium i n comparison w i t h t h e pre-flight values. The in-flight

data have some elements of doubt about them because of correction

f a c t o r s f o r c r e a t i n i n e excretion, but t h e post-flight/pre-flight

comparisons are q u i t e s i g n i f i c a n t . Next slide, please.

(Figure 8)

These are t h e a c t u a l figures f o r urinary excretion of t h e

various elements. There is a tremendous number of numbers on t h i s

slide; t h e standard deviation f o r each of these values i s not l i s t e d

here. The standard deviations were of t h e order of 20% of t h e

mean and were q u i t e similar f o r most of t h e figures. There w a s

a s i g n i f i c a n t increase i n urinary excretion of calcium; there w a s

no s i g n i f i c a n t change i n magnesium (I'm t a l k i n g only about t h e

command p i l o t ) . There w a s a s i g n i f i c a n t increase i n urinary excre-

t i o n of phosphate, a decrease i n nitrogen, but i f you r e c a l l

(Figure 3 ) , t h e nitrogen intake in-flight w a s much lower. The

sodium excretion in-flight w a s Increased, however, not by a


s i g n i f i c a n t amount. Urinary potassium was not s i g n i f i c a n t l y

changed i n t h e command p i l o t .

The p i l o t , on t h e other hand, d i d show a s i g n i f i c a n t change.

The point here again is t h e f a c t o r of interindividual. variabili-

ty. I n addition, t h e r e is a r e l a t i o n s h i p between t h e d i e t a r y in-

take and t h e urinary excretion i n some instances. Urinary mag-

nesium is related t o dietary intake of magnesium. Urinary phos-

phate, generally, i s related t o t h e intake, and t h e f a c t t h a t

t h e phosphate intake was considerably lower i n f l i g h t while t h e

phosphate excretion w a s considerably higher means t h a t t h e in-

creased lass of phosphate i s s i g n i f i c a n t . May I have t h e next

slide, please.

(Figure 9 )
I'll t r y t o summarize t h e data very rapidly with a series

of balance slides. These are p l o t t e d by the t r a d i t i o n a l tech-

nique of A l b r i g h t and Reifenstein; i n t a k e i s p l o t t e d down from t h e

zero f i n e , excretions are then p l o t t e d up from t h e intake. Sweat

l o s s e s were i n s i g n i f i c a n t throughout. These comprised less than

one milliequivalent of calcium, l e s s t h a n 20 milligrams a t any

phase of t h e study. Urinary lasses of calcium increased in-flight,

and increased by a g r e a t e r amount during t h e second week of f l i g h t .

The intake vas less in-flight by about 300 milligrams and t h e net

r e s u l t w a s s l i g h t l y negative calcium balance. The difference be-

tween t h e balance pre-flight and i n - f l i g h t i s s i g n i f i c a n t , but i n

terms of a c t u a l amount lost from t h e body, t h i s i s not a great

139
dI

loss. Post-flight, t h e r e appeared t o be a s l i g h t retention. The

a c t u a l balance post-flight was very similar t o t h a t pre-flight,

indicating t h e r e probably had not been s i g n i f i c a n t losses. Next

s l i d e , please.

(Figure 10)

For t h e p i l o t , t h e l o s s e s were even less s i g n i f i c a n t insofar

as calcium i s concerned and one cannot r e a l l y d e t e c t any serious

loss of t h i s element. Next slide, please.

(Figure 11)

Nitrogen balance i n t h e command p i l o t , which is related t o

p r o t e i n metabolism and muscle metabolism, on the other hand, d i d

show s i g n i f i c a n t l o s s e s of nitrogen during t h e f l i g h t phase which

p e r s i s t e d post-flight despite an increase i n d i e t a r y intake. Next

slide, please .
(Figure 1 2 )

This p i l o t showed a similar loss in-flight, but then shoved

a r e t e n t i o n post-flight when t h e d i e t a r y intake increased. Next

s l i d e , please.

(Figure 13)

The phosphate balances show t h e most s i g n i f i c a n t l o s s e s ob-

served; we have no explanation f o r t h i s as y e t ; we will be t r y i n g

t o c a l c u l a t e t h e s e losses i n terms of nitrogen and bone equivalents.

There w a s a definit,e loss of phosphate despite a decreased d i e t a r y

intake. Urinary yhosphate increased in-flight indicating s i g n i f i c a n t

140
l o s s from t h e body. Next s l i d e .

(Figure 1 4 )

The same w a s seen f o r t h e p i l o t , a s i g n i f i c a n t l o s s of phos-

phate. Next slide.

(Figure 15)

I'm not going t o go i n t o d e t a i l concerning sodium and potas-


sium, but w i l l simply i n d i c a t e t h a t t h e negative balance of sodium

t h a t was seen w a s probably due t o a change i n t h e intake. The

sodium intake w a s q u i t e high pre-flight, w a s s i g n i f i c a n t l y lower

i n - f l i g h t , and w a s back up t o t h e higher values post-flight. How-

ever, post-flight t h e r e was a d e f i n i t e r e t e n t i o n of sodium.

VOICE: Have a l l of these been corrected f o r t h e creatinine?

DR. LUTWAK: A l l of t h e in-flight d a t a have been corrected

f o r t h e creatinine. It w a s impossible t o p l o t any balance d a t a

without corrections. The s i g n i f i c a n t finding with sodium balance

w a s a d e f i n i t e r e t e n t i o n of sodium post-flight.

VOICE: Is t h e height of t h a t sodium output block i n t h e in-


f l i g h t area less than t h a t i n t h e pre-flight area?

DR. LUTWAK: The urinary output w a s J u s t about t h e same, but

post-flight t h e r e w a s a d e f i n i t e retention. Next s l i d e , please.

(Figure 16)

The same was seen f o r t h e other man, a very d e f i n i t e reten-

t i o n of sodium post-flight which c o r r e l a t e s with t h e aldosterone

values t h a t D r . Lipscomb reported earlier.

VOICE: Do you have any measurements t h a t would show whether

141
o r not your c r e a t i n i n e correction i s valid?

DR, LUTWAK: Well, we've done t h i s w i t h a g r e a t many other

smples. We've taken individuals i n whom we've collected t h e

u r i n e i n separate portions throughout a 24 hour period, analyzed

t h e separate portions, and analyzed t h e t o t a l , and then attempted

t o apply correction factors. I f w e have more than 2/3 of 24 hour

collection, then t h e correction f a c t o r appears t o be valid. If

we have less than that, t h e values are not v d i d . There is a

diurnal v a r i a t i o n i n c r e a t i n i n e excretion and t h e r e a r e d i u r n a l

v a r i a t i o n s i n t h e excretion of other metabolites which do not

always coincide. With a 2/3 of t o t a l sample, t h e r e i s a fair

degree of approximation. We had, I believe, about a 2/3 sample

i n each case, and therefore we have a f a i r approximation f o r t h e

24 hours. This appears t o be valid within about 20%. Next slide.

(Figure 17)

Potassium balances a r e going t o give us a l o t more trouble

because potassium intake in-flight w a s so d i f f e r e n t from t h e pre-

and post-flight phases t h a t t h i s i n itself may have introduced

f a c t o r s which would have changed t h e production of aldosterone

and other hormones which a r e dependent upon potassium economy of

t h e body, Here it i s hard t o say whether we are seeing a cause

o r an e f f e c t because of t h e very d i f f e r e n t intakes. The reason

f o r t h i s difference i n intake w a s t h a t pre-flight and post-flight

t h e men ate a good deal of fresh f r u i t s and vegetables. In-

f l i n h t . of course. t h e menu w a s a l l prepared dehydrated food much

142
lower i n f r u i t and vegetable content and therefore i n potassium

content. N e x t slide, please.

(Figure 18)

The same is seen f o r t h e other man i n regard t o potassium

balance. Next slide, please,

(Figure 19)

This i s a summary of a l l of t h e balances t h a t have been

calculated thusfar. The chart summarizes t h e balance figures i n

terms of a c t u a l numbers. There are s i g n i f i c a n t differences i n

balance f o r calcium between the pre-flight and in-flight phases.

This i s possibly due t o d i e t a r y intake. Significant differences

i n magnesium were d e f i n i t e l y due t o d i e t a r y changes. Signifi-

cant differences occurred i n phosphate balance which we have not

explained. Significant differences i n nitrogen balance were def-

i n i t e l y due t o dietary intake v a r i a b i l i t y . Sodium and potassium

balance changes w e r e probably a l s o due p a r t l y at l e a s t t o d i e t a r y

variability.

I n summary, we have t r i e d t o do a balance study. We knew

i n i t i a l l y t h a t what we were attempting was an estimation of t h e

f e a s i b i l i t y of carrying out a long-term balance study under ex-

tremely arduous conditions, arduous f o r t h e investigator, but

even more arduous f o r t h e subjects. We f e e l fortunate t h a t we

were able t o obtain any type of data. We have not obtained suf-

f i c i e n t data t o be a b l e t o cane t o any conclusions. To f o r e s t a l l

the up-coming question, I don't t h i n k we can say t h a t providing


high calcium d i e t s o r low calcium, feeding high protein intakes

o r low protein, may be of any benefit o r of any harm u n t i l we

have more data of t h i s type, u n t i l we have more opportunity t o

evaluate t h i s type of study. This meeting can be used as an oc-

casion t o plead. We'd l i k e t o plead f o r longer pre-flight con-

t r o l phases and longer post-flight control phases so t h a t we

can i n t e r p r e t some of t h i s data more s i q n i f i c a n t l y .

VOICE: Does t h a t profound difference i n t h e potassium in-

t a k e during f l i g h t automatically c a s t a considerable amount of

doubt on t h e significance of t h e aldosterone observations i n

flight?

DR. LUTWAK: Yes, because low potassium d i e t s can change

aldosterone s e c r e t i o n as has frequently been shown a l s o f o r low

sodium d i e t s .

VOICE: I guess I can't argue t h a t it would be nice t o have

longer pre- and post-flight controls, but more p a r t i c u l a r l y , it

appears t h a t you need a b e t t e r control of t h e a c t u a l d i e t .

DR. LUTWAK: There were mechanical problems and technical

problems that have been discovered and I hope we won't run i n t o

t h e same ones next time around. This w a s a learning process f o r

us; it w a s a learning process f o r everyone involved i n the study.

W e had t o l e a r n where t h e e r r o r s could come i n , and I t h i n k we

have n'ow.

VOICE: Have you r e a l l y sat d o q now and set up a set of

s p e c i f i c a t i o n s , I c a l l it, as t o how you're going t o carry out

144
t h i s experiment, if you have t o carry it out again, so t h a t we

don't have unanswered questions about how much they've eaten i n

the way of potassium and how much i n calcium? It should be speci-

f i e d t h a t t h e c r e w i s t o eat meals i n a c e r t a i n order. The

crew should understand why it is important t o t h e whole experi-

ment.

DR. LUTWAK: These are t h e o r i g i n a l specifications t h a t w e r e

w r i t t e n i n t o t h e first description of t h e M-7 project. All we

can do is t o r e i t e r a t e them and hope t h a t next time other prob-

lems won't come alonq t h a t w i l l confuse and confound t h e issue.

VOICE: Do you want us t o accept t h a t experiment w i t h t h e

same ground r u l e s except f o r a f e w minor changes?

DR. LUTWAK: "hat would be a very good approximation. Yes.

VOICE: It would be a valid experiment, then.

DR. LUTWAK: It would be a b e t t e r approximation than t h i s one;

it would be a more v a l i d one than t h i s one.

VOICE: It seems t h a t you a r e saying t h a t due t o t h e fact

t h a t t h e d i e t was switched i n the in-flight area - it w a s very d i f -


ferent from t h e pre- and post-flight area - t h a t much of t h i s i s
r e a l l y masked by the change of d i e t . Now, t h i s would i n d i c a t e t h a t

if you r e a l l y want t o get meaningful data, you have t o put t h e crew

f o r t h e e n t i r e pre-, in-, and post-flight periods on t h e same d i e t

formula.

DR. LUTWAK: The i d e a l s i t u a t i o n which we've t a l k e d about but

which apparently i s not f e a s i b l e a t present i s t h e use of a formula

145
diet. A formula diet would be identical pre-flight, in-flight, and

post-flight.
VOICE: It seems to me that it is important to try to be sure

that we understand all of these variables and also understand how

this works on the ground as well as in-flight, I would think, and

I haven't heard it discussed, that one could duplicate every-


thing here, including keeping people in bed for the duration of

a 14-day flight or 28 days, and run the same type of blood tests

and urine tests,


DR. LWAK: That's been done many times. The ultimate ques-

tion still remains..,


VOICE: H o w does this compare with all of these balance stud-

ies?
DR. LUTWAK: Well, this comparison is what we have attempted,

but we can't do it successfully because of the variability of the

conditions encountered in-flight. We can say that there seems to

be a tendency so far as calcium, nitrogen, and phosphate metabolism


are concerned, for parallel results to have been observed as a re-

sult of weightlessness as compared with the bedrest studies.


VOICE: Do we have a bedrest study now that has the same di-
etary variations that this flight had?

DR. LIJTWAK: No, because we prefer to study one variable at


a time. Here we have about 15 variables simultaneously. This is

a difficult experiment to interpret. What we would like to do is

to isolate variables.
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S OLU 61LlTY
RECOVERY

ITRIG ACID

Fig. 118. Effect of immobilization on the urinary excretion of calcium and citric
acid and on urinary pH in four normal male aubjecta. Daily calcium intake was
0.852 gm.for subject E.M., 0.920 gm.for aubjecta C.O., A.S. and S.W.

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Medical Experiment ~008
INFLIGHT SLEEP ANALYSIS

Principal Investigators
Peter Kellaway, Ph. D.
Professor of Physiology
Department of Physiology
Baylor University College of Medicine and
The Methodist Hospital, Houston, Texas

Robert L. Maulsby, M.D.


Assistant Professor of Physiology
Department of Physiology
Baylor University College of Medicine and
The Methodist Hospital, Houston, Texas
MEDICAL EXPERIMENT ~ 0 0 8
t

1WLIC;HT SLEEP ANALYSIS

The electroencephalogram of Cormnand Pilot Frank Borman

was recorded continuously during the first two days of the

Gemini VIT flight in December, 1965. This first U.S. attempt

to record EEG during orbital flight was designed to study sleep

cycles during flight and to assess the effect of "weightless-

ness" upon the electrical activity of the brain. This report

gives the technique used and the preliminary results of vis-


ual interpretation of the record.
The recording was of good technical quality. The two
sleep periods which occurred during the record were evaluated

visually for depth of sleep versus time on a minute-to-


minute basis. The first sleep period was found to be inade-
quate in terms of depth and length, but the second sleep

period was normal. The tracing during the alert state,


including ascent and orbital flight, showed no pathological

changes and no definite alterations which could be attri-

buted to "weightlessness. I ' It is concluded that these

preliminary results confirm the view that orbital flight

has no apparent deleterious effect on cerebral function.


OBJECTIVES

Recordings of the electroencephalogram (EEG) on a p i l o t

during o r b i t a l f l i g h t were made f o r t h e first time i n t h e

U.S. space program on t h e Gemini V I 1 f l i g h t . The immediate

goal of t h i s project (called the M-8 experiment) was t o ob-

t a i n an objective evaluation of the p i l o t ' s sleep p a t t e r n i n

order t o discover any deviation from p a t t e r n s recorded on

e a r t h and t o assist i n revealing f a c t o r s which may i n t e r f e r e

with sleep i n an o r b i t i n g spacecraft, since some d i f f i c u l t y

sleeping has been reported by several astronauts. I n addition

t o t h i s p r a c t i c a l goal, t h e experiment was a l s o intended t o

determine the e f f e c t s , i f any, of "weightlessness" on t h e

e l e c t r i c a l a c t i v i t y of the brain.

This report gives the technique of EEG recording used

i n the Gemini V I 1 f l i g h t and presents the r e s u l t s of v i s u a l

i n t e r p r e t a t i o n of t h e data. Computer analysis of t h e same

data w i l l be reported by others.

METHODS

Two channels of EEG data from Command P i l o t Frank

Borman were recorded on an onboard tape recorder. The

electrodes were chlorided s i l v e r d i s c s imbedded i n a l u c i t e

cup. These were f i l l e d with NASA e l e c t r o l y t e j e l l y and

attached t o the scalp with Eastman 910R adhesive over s i t e s


which had been denuded with depilatory cream and d r i l l e d

168
4
w i t h a high-speed d e n t a l burr. EEG channel No. 1 w a s derived

from t h e l e f t c e n t r a l and l e f t o c c i p i t a l electrodes; EEG

channel No. 2, from t h e midline c e n t r a l and midline o c c i p i t a l

electrodes. The l i n i n g material of the astronaut's helmet

was designed with indentations over each electrode position

i n order t o avoid pressure on the electrodes. Transistorized

s i g n a l conditioners were worn i n pockets of t h e astronaut's

underwear.

The onboard tape recorder w a s capable of recording 100

hours of data on one r e e l of magnetic tape. After recovery

of t h e spacecraft, t h e data w a s re-recorded onto another tape

having a standard I R I G format. This tape was written out on

an ink-writing oscillograph a t an equivalent real-time paper

speed of 15 mm/sec f o r v i s u a l i n t e r p r e t a t i o n .

RESULTS

Quality and Quantity of Data--Most of the EEG data

recorded was of excellent q u a l i t y from t h e standpoint of

visual interpretation. During r e s t and sleep, t h e tracings

were as good as any obtained on earth, even i n carefully-

controlled laboratory s i t u a t i o n s . When the astronaut was

a l e r t and a c t i v e , t h e record contained electrode movement

and muscle p o t e n t i a l a r t i f a c t s which tended t o obscure

the normal low voltage wakeful pattern. Except during meals,

however, t h e a r t i f a c t s i n a c t i v e periods were not of such


magnitude as t o have prevented detection of pathological

changes, since t h e l a t t e r a r e almost always characterized by

an increase i n voltage and a decrease i n frequency.

Figure 1 i s a bar graph representing quantity of data

recorded. A t o t a l of 54 hours and 43 minutes of i n t e r p r e t a b l e

EEG data was obtained, s t a r t i n g from 15 minutes p r i o r t o l i f t -

off. EEG derivation No. 1 ( l e f t c e n t r a l t o o c c i p i t a l ) became

noisy after 25 hours, 50 minutes of f l i g h t (point B i n Figure 1)

and it ceased t o function a f t e r 28 hours, 50 minutes (point C) .


EEG derivation No. 2 (midline c e n t r a l t o o c c i p i t a l ) gave

a r t i f a c t - f r e e data up t o 43 hours, 55 minutes (point D ) , and

ceased t o function a f t e r 54 hours, 28 minutes.

A l s o indicated i n Figure 1 a r e t h e two sleep periods

(shaded areas) which occurred during t h e recording, one

period during which the astronaut closed h i s eyes f o r t h e

greater p a r t of two hours (between dotted l i n e s ) , and meals

(black rectangles). The s l e e p periods are discussed below.

The meals (or periods of gum chewing) are noted because they

represent temporary interruptions i n t h e i n t e r p r e t a b i l i t y

of t h e EEG data due t o a r t i f a c t s produced by rhythmic chewing

mot ions.

EEG P a t t e r n i n the Active State--Examples of the EEG

p a t t e r n i n t h e active s t a t e are shown i n Figures 2B, 3, and

3B. Before l i f t o f f (Figure 2B) the record showed occasional


astronauts' report t h a t they were able t o exclude sunlight

from the spacecraft completely, the shadow h i s t o r y i s the only

factor showing a suggestive relationship with arousal. Of

the t o t a l one-minute epochs i n the two sleep periods, 26.4 per

cent contained some arousal-type EEG a c t i v i t y (EO and stage 0

on Figure 8). O f the sleep minutes recorded while the space-

c r a f t was i n sunlight. 35.2 per cent showed some arousal,

whereas only 9.3 per cent showed arousal while the spacecraft

was i n the e a r t h ' s shadow.

DISCUSSION

The Russians began i n f l i g h t EEG recording with the

f l i g h t of Nikolayev and Popovich and have continued t o monitor

EEG i n a l l subsequent f l i g h t s . Judging from the few available

English translations of t h e i r reports >7%he Russians use only

one EEG channel, which can be telemetered t a earth or recorded

on board. The two electrodes (mid-occipital and mid-frontal)

are held i n place by an e l a s t i c cap o r band. The quantity

of EEG data obtained on e a r l i e r f l i g h t s i s not mentioned, but

on the recent three-man flight (Komarov, Feoktistov, and

Yegorov), only b r i e f (about 40 second) i n t e r v a l s of EEG data

were recorded periodically during the f l i g h t while the crew

members were performing hand and eye coordination t e s t s . No

mention has been made of EEG recordings while the cosmonauts

were asleep i n o r b i t .
second) a c t i v i t y i n the a l e r t s t a t e , but t h i s could not be

evaluated quantitatively by visual means.

EEG Pattern During SleeE--As shown i n Figure 1, twr, sleep j

periods occurred during the recording. The f i r s t sleep period

occurred a t 14:07 hours ( f l i g h t time) and l a s t e d only 1hour,

28 minutes. The second sleep period began a t 33:lO hours and

l a s t e d 8 hours, 46 minutes.

The E%G patterns during sleep are very d i s t i n c t i v e and,

since the astronaut i s quiet, no a r t i f a c t obscures the record.

Figures 5, 6, and 7 i l l u s t r a t e the EEG patterns a t various

stages or levels of sleep. Stage 0 consists of a f u l l alpha

rhythm, and i s interpreted as the r e s t i n g , eyes-closed pattern.

I n the t r a n s i t i o n from stage 0 t o stage 1 sleep (Figure 5A and B),

the alpha rhythm decreases i n voltage and i s gradually replaced

by low voltage t h e t a a c t i v i t y , mixed with some l o w voltage f a s t e r

components; t h i s i s the f i r s t EEG sign of drowsiness. Stage 2

sleep, o r l i g h t sleep, i s characterized by moderately high vol-

tage, semi-rhythmic and rhythmic t h e t a a c t i v i t y and sharp

t r a n s i e n t waves. This a c t i v i t y i s a mixture of o c c i p i t a l and cen-

t r a l sleep characters (Figure 5C). Stage 3 sleep, o r moderate

sleep (Figure 6A), i s characterized by sigma a c t i v i t y (14 cps),

mixed with vertex transients and some low voltage d e l t a a c t i v i t y

(1-3 cps). Stage 4 sleep, or deep sleep, i s distinguished by

almost continuous high voltage d e l t a a c t i v i t y , as shown i n


Figure 6B. When the subject arouses, o r i s aroused, from

sleep (Figure 6 6 ) , the record quickly reverts t o stage 0, o r

the r e s t i n g , awake pattern.

The recently-described "paradoxical" phase of sleep i s

d i f f i c u l t t o recognize without simultaneous recordings of eye

movement (electro-oculogram) . The sample i n Figure 7, which

resembles a mixture of stages 1 and 2 sleep, shows some of the

EEG c h a r a c t e r i s t i c s observed during "paradoxical" sleep with

rapid eye movements: runs of 3 per second "saw-tooth" waves,

runs of low voltage alpha a c t i v i t y and t h e t a a c t i v i t y , low

voltage fast a c t i v i t y without spindles of sigma a c t i v i t y , and

occasional very s l o w transients having a period of more than

one second. This type of pattern, which might represent

"paradoxical" sleep, o.ccurred f o r t w o f a i r l y long sections

during the second sleep period i n flight--beginning a t ll:O5

hours and 14:ZO hours.

The sleep periods were located by v i s u a l l y scanning the

write-out of the tape. Each minute of sleep was c l a s s i f i e d

as t o stage of sleep according t o the above c r i t e r i a , and

p l o t t e d graphically versus time, as shown i n Figwe 8 wfiich

i l l u s t r a t e s the sleep p a t t e r n of both f l i g h t sleep periods,

as w d l as a control sleep period recorded p r i o r t o f l i g h t .

The uppermdst l e v e l on the v e r t i c a l axis represents the eye-open,

a l e r t pattern. The next l e v e l i s the eyes-closed, r e s t i n g

pattern, or stage 0. The heavy horizontal l i n e i n the center of

173
stage 0 represents the d i v i s i o n between waking and sleeping

EEG p a t t e r n s . The next four l e v e l s represent the four stages

of sleep from l i g h t sleep down t o deep sleep. When, as i s the

usual case, more than one EEG, sleep stage was seen during a

one-minute epoch, the v e r t i c a l l i n e f o r t h a t epoch was drawn

t o overlap the tm or mare stages seen during t h a t minute. The

horizontal axis of these graphs i s marked i n elapsed flight

time. The control sleep period (upper l e f t graph i n Figure 8)

was s i m i l a r l y analyzed f o r comparison of r a t e of f a l l i n g t o

sleep and depth, but the o v e r a l l p a t t e r n cannot be compared t o

t h e f l i g h t periods since t h e subject was not allowed t o complete

a spontaneous sleep period.

The depth of sleep p a t t e r n i n t h e second sleep period

c l e a r l y shows t h e normal c y c l i c a l variations i n l e v e l of sleep

described by Dement and Kleitman.* The t r a n s i e n t arousals

within t h e period, however, seem t o be s l i g h t l y more frequent,

and f u l l y a l e r t p a t t e r n s ( l e v e l s above the horizontal black bar

i n Figure 8) are seen more often i n t h i s period than were

found i n Dement and Kleitman's laboratory studies of normal

individuals.

An attempt was made t o c o r r e l a t e t h e t r a n s i e n t arousals

from sleep with various environmental f a c t o r s , such as s u i t

and cabin temperature variations, cabin pressure variations,

and the shadow h i s t o r y of the spacecraft. I n s p i t e of the

174
runs of low voltage alpha rhythm superimposed upon a somewhat
unsteady baseline and mixed with eye-blink potentials ( t r a n s i e n t

downward deflections). Occasional runs of low voltage 5-7 cycle

per second a c t i v i t y also appeared i n the record; these resemble

t h e t a a c t i v i t y but are d i f f i c u l t t o distinguish with c e r t a i n t y

from rapid ocular o r eyelid movement potentials. During ascent

(Figure 3A) continuous high frequency muscle potentials were

superimposed upon the trace. After 24 hours i n o r b i t (Figure 3B)

the record showed a more "relaxed" pattern, with more rhythmic

alpha a c t i v i t y and l e s s muscle p o t e n t i a l a r t i f a c t .

During meals, or when the astronaut chewed gum (Figure 4 A ) ,

the record consists of high voltage 1.5-2.0 cycle per second

waves mixed w i t h muscle potentials. These a r t i f a c t s , produced

by rhythmic chewing motions, obscure cerebral potentials entirely.

When the astronaut closed h i s eyes, such as i l l u s t r a t e d

i n Figure 4B, the record shows a strong alpha rhythm and i s f r e e

of a r t i f a c t . This sample i s from a two-hour period i n the f i r s t

day of f l i g h t during which the astronaut apparently tried t o

sleep but was unable t o do so.

The e n t i r e wakeful record (which constituted 77.5 per cent

of the t o t a l recording) was visually scanned f o r evidence of EEG

changes of c l i n i c a l significance; none were found, e i t h e r during

ascent o r i n o r b i t . By comparison with the p r e f l i g h t baseline

study, there seemed t o be s l i g h t l y more t h e t a (4-7 cycles per

second) activity.

3-75
The EEG recording on Gemini VI1 i s , therefore, probably

the most complete study yet made during o r b i t a l f l i g h t i n

terms of number of channels, length of recording, and

variety of su3ject a c t i v i t y and s t a t e s of consciousness. Two

channels of EEG d a t a were recorded continuously from before

l i f t - o f f through the f i r s t day of f l i g h t . The recording

thus covers ascent, three working periods of o r b i t a l f l i g h t ,

and two sleep periods. It i s hoped t h a t a longer-lasting


electrode system can be developed i n the near future so

t h a t a recording can be made throughout an e n t i r e f l i g h t ,

including re-entry and recovery.

From a medical point of view, the r e s u l t s of the current

study were e s s e n t i a l l y negative i n t h a t no pathological EEG

changes were observed, and visual inspection of the tracing

revealed no changes ~ i c could


h be a t t r i b u t e d t o the "weightless"

state. Furthermore, it i s d i f f i c u l t t o draw conclusions from

the two recorded sleep cycles. The f i r s t sleep period was

d e f i n i t e l y inadequate i n terms of length and depth of sleep,

but the p a t t e r n was t y p i c a l of ordinmy insomnia or disturbed

sleep, which can e a s i l y be exrplained on the basis of the

understandable anxiety of the s i t u a t i o n and the unique con-

d i t i o n s of o r b i t a l flight. The second sleep period was ade-

quate i n terms of depth and length, but t h i s cannot be used

as d e f i n i t e evidence against o r b i t a l sleep disturbance since


the p i l o t was probably quite fatigued due t o loss of sleep

i n t h e f i r s t sleep period. Sleep patterns i n subsequent

sleep periods l a t e r i n the flight will have t o be obtained

i n order t o a r r i v e a t any d e f i n i t e conclusions as t o whether

--
o r b i t a l f l i g h t per se tends t o d i s t u r b sleep.

The EEG's of t h e cosmonauts were analyzed i n terms of

alpha, beta, and t h e t a indices. I n general, most showed an

i n i t i a l decrease i n alpha index (per cent t i m e alpha) e a r l y

i n the f l i g h t , followed by a progressive increase i n alpha


index. These changes, the Russian authors opine, are indicative

of a "poorly defined f a t i g a b i l i t y of the cosmonauts," but a r e

not pathological. The EEG recoydings from Tereshkova Were

somewhat d i f f e r e n t i n t h a t she showed an augmentation of t h e t a

index during ~ e i g h t l e s s n e s s . ~Since we have not found such

index determinations t o be usef'ul c l i n i c a l l y , t h i s type of

analysis has not been c a r r i e d out on EEG records from Gemini

VII. Other investigators will employ computer analysis of

the EEG data from Gemini V I 1 i n order t o search f o r any changes

which are not evident i n visual interpretation.

CONCLUSIONS

(I) "he f i r s t U. S. attempt t o record the electro-


encephalogram during o r b i t a l f l i g h t was successful. It

demonstrated t h a t it i s possible t o obtain good-quality EEG


tracings f o r a r e l a t i v e l y long period €rom an astronaut

during ascent, while operating the vehicle i n o r b i t , and

during sleep.

(2) Visual interpretation of the EEG tracing revealed no

abnormalities and no obvious changes a t t r i b u t a b l e t o "weight-

lessness."

(3) Depth of sleep patterns of the f i r s t two sleep


1
periods during the flight were not unusual. The f i r s t sleep

period was inadequate i n terms of depth and length, but the

second sleep period was normal.

(4) The r e s u l t s of t h i s preliminary EEG study confirm

the view t h a t o r b i t a l f l i g h t has no apparent deleterious

e f f e c t on the a c t i v i t y of the brain.

378
REFEBE3CES

1. Akulinichev, I. T., Bogdanov, V. V,, Maksimov, D. G.,

and Popov. I. I.: Rezul'taty nekotoryk;h elektrofiziologicheskikh


issledovaniz na korable "Voskhod." Paper presented at the

XVI International Astronautical Congress, Athens, September

13-18, 1965.

2. Dement, W., and Kleitman, N.: Cyclic Variations in EEG

Dpring Sleep and Their Relation to Eye Movements, Body

-
Motility and Dreaming. Electroenceph. Clin. Neurophysiol,

9:673, 1957.

3. Parin, V. V., Volynkin, Y. U. M., and Vassilyev, P. V.:


Manned Space Flight--Some Scientific Results. In Florkin,
M.: Life Sciences and Space Research, Vol. 111. North

Holland Pub. Co., Amsterdam, 1965.

4. Shackel, B.: Skin-drilling: A Method of Diminishing

Galvanic Skin Potentials. her. J. Psychol, 72: 114, 1959.


Fig. 1 Bar graph representing quantity of EZG data obtaiued.
See text for aplanatlr>n.
Fig. 2 A. (Vpper two tracings): Write-out of calibration sigrtals
w h i e h were applied t o the data tape prior t o liftoff. A l l

EEG illustrations in this paper used t h i s gsl;Ln and chart

Speed.

3. (mwer two tracings): EEO pattern prior t o l i f t o f f .


Fig. 3 A. (Upper tvro tracings): Hco pattern dur- ascent, near
peak acceleration.

3. (Lower two tracirys): EB3 pattern d u r a orbital flight.&

Fig. 4 A. (Vpper two tracings): Artifacts produced i n EECC pattern


by rbytbmic chewing &tiow.

B. (mer two tracings): Fully expressed alpha rbytbm

present when eyes are closed while p i l t is alert.


Fig. 5 A and B. (Upper two tracings): Illustration of the transi-
tion from the alert, resting pattern t o drmsineers, or
stage 1 sleep.
C. ( m e r trace): L i g h t sleep pattern, or stage 2 sleep.

Fig. 6 A. ( @ p e ~trace): stage 3 sleep, or moderate sleep.


B. (Mtddle trace): Deep sleep, or stage 4.
C. (ulustration of a transient arousa,l from stage 4 sleep
t o stsge 0.

Fig. 7 Continuous tracings showing a m;lxture of sleep stages 1 and


2. This pattern occurred for long intervals and resembles
the EBG seen during the rapid eye movement phase of sleep,

or "pruradoxial sleep "

180
Pig. 8 Graphs showing the minute-to-minute variations in depth
of sleep. See text for explanation.
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a
EXPERIMENT M-9, HUMAN OTOLITH FUNCTION:

MEASUREMENTS IN GEMINI FLIGHTS V AND VI1

Rinci pal Investigators

NAME Ashton Graybiel, Me D .


TITLE Director of Research
LOCATION Naval Aerospace Medical Institute, Pensacola, Florida 32512

NAME Earl F. Miller, II


TITLE Head, Physiological Optics Branch
LOCATION Naval Aerospace Medical Institute, Pensacola, Florida 32512
EXPERIMENT M-9, HUMAN OTOLITH FUNCTION:

MEASUREMENTS IN GEM1N1 FLIGHTS V AND VII*

The otolith orggns and semicircular canals which comprise the

nonacoustic labyrinth i n man contain the only sensory receptors

which specifically react to gravitoinertial forces. Many investigators

refer to them collectively as the vestibular organs, which emphasizes

the difficulties under many circumstances of distinguishing between

these two closely related sensory systems. Under *ordinary conditions,

the physiological stimolus to the otoliths i s linear and to the canals,

angular acceleration. Thus, the canals are stimulated by the inertial

forces generated by the rotary movements of the head (body) and sob-

serve such normal functions as sensing rotation and aiding i n visual

tracking and i n maintaining postural equilibrium. The otolith organs

are stimolated by gravity, by changes i n the gravitoinertial force

vector with respect to the head, and by changes i n position of the

head with respect of this vector; they contribute to such useful functions

*Answers to questions raised at the time of this presentation have been

incorporated in the text.


as the perception of linear motions, orientation to the upright, and

maintenance of postural equilibrium Loss of the semicircular canals

in man under terrestrial conditions results i n qualitative loss of certain

functions whereas loss of otolith function results mainly i n quantitative

deficiencies; the receptor organs responding to mechanical forces

including the direct and indirect effects of weight often act in a

complimentary or synergistic fashion

The vestigular organs are affected quite differently in weightless-

ness, and their individuality i s emphasized. At rest there i s

"physiological, deafferentation" of the otolith apparatus, but there is

no corresponding effect on the canals. With movement of h e body (head)

the angular accelerations generated would stimulate the canals much the

same as under terrestrial conditions, but the smal I linear accelerations

might not aIways,constitute an adequate stimulus to the otoliths and, when

they di k would not provide a cue to the upright of the spacecraft. Stated

differently, when a person makes his first transition into weightlessness,

the normal stimulus to the otolith apparatus i s lost for the f i r s t time i n his

life. It i s analogous to closing the eyes, with the important difference

that we are habituated to eyes closed as well as open. In the absence

of linear accelerations, cues provided by contact with the environment

are i n response to mechanical force.


Although a unique and remarkable opportunity exists i n orbital

space flight to investigate many aspects pertaining to the role of

the otoliths and canals, such experimentation i s difficult and only

limited possibilities were afforded i n the Gemini flights. The

experiment agreed upon comprised two distinct but not wholly un-

related parts. One consisted of the pre- and post-flight measurement

of ocular counterrolling, a measurement of otolith function (1). The

other was concerned with the influence of nonvisual cues on spatial

localization. Here the astronauts' task was to set a luminous line to

the horizontal i n an otherwise dark visual field; pre- and post-flight

i t was set to the Earth horizontal, and inflight, to an element i n the

spacecraft horizontal with respect to the astronaut. The data were

collected under the immediate supervision of Dr. Earl F. Miller; the

Center investigator i n GT V was Dr. John Billingham, and i n GT MI,

Mr. Richard Waite.

SPATIAL LOCALIZATION

The purpose of this experimental probe was to compare the

influence of nonvisual sensory information under terrestrial and weight-

less conditions on the visually perceived direction of space. Data


obtained from earlier experiments not only are relevant for

comparative purposes but also serve as a necessary introduction.

SE NSORY SYSTEMS

It is generally held that physical space is not provided by a

specific quality of sensations themselves but by a construct placed

upon them. It is acquired as man becomes aware of the external

environment in relation to himself. Under natural living conditions

the most important cues for the perceived direction of space are

furnished by the visual and gravitoinertial force environments. The

best concordance between the two i s manifested with man upright,

and its achievement represents one of the most dramatic manifestations

of man's adaptation to his outer environment. In the course of his

primitive sense experiences, man's perception of the visual world

underwent a reversal to conform with the gravitational upright, and

the central nervous system integrative mechanisms, continuously

ensuring spatial orientation, constitute an elegant example of homeostasis.

It i s necessary to keep in mind the evolutionary manner in which

orientational homeostasis was acquired to appreciate properly how and

why it is disturbed when man extends his natural abilities by artificial

meansD In adjusting to these new force environments man at once

reflects his habituation to specific natural terrestrial conditions and


-

the plasticity of his central nervous system.

194
I n Figure 1 i s shown a simplified analysis of cues to space perception

provided under terrestrial conditions and some of the possibilities for

interaction among them. The great concordance between cues from

the gravitational and visual environments is obvious i n natural environ-

ments and yet more so i n artificial ones which are based on the

gravitational coordinate system.

Some of the possibilities for interaction can be artificially

contrived, not only by manipulations of the visual and force environments

but also by the use of subjects with or without labyrinthine function.

In general, manipulations are far easier to accomplish i n the visual

than in the force environment; moreover , with vision a unique situation

exists i n which one can study nonvisual influences on visual space

localization i n the absence of visual cues to space. This i s represented

by the broken lines i n Figure 1. It i s important to emphasize that i n

the articulation between sensory information from the visual and force

environments, visual cues are inadequate and only a very slight

influence i s demonstrable.

- -----
Examples of Interactions Between Cues From Visual and Force

Environments

In Figure 2 (top) i s shown a naive normal subject on an open

centrifuge and facing the center of rotation. When he is exposed


to a centripetal force of 1 .O g unit, the centrifuge appears to slope

upward away from him and the room appears similarly sloped (2).

This is at once a demonstration of preternatural control over the

force environment and a partial conformity of the visually perceived

upright to the gravitoinertial upright. This has been termed the

oculogravic illusion (3) based on the Earth reference.

In Figure 2 (below) h e is exposed to 2.0 g units, and, some

persons at least, soon feel as if they are stationary and on their

back and perceive the room rotating around them. This is probably

analogous to experiences of aviators in certain types of spin (4).

Not only are visual cues overwhelmed but also there is over-

compensation with reference to the gravitoinertial upright. The

curious reversal with regard to relative motion between centrifuge

and room might have its genesis in the fact that the force

environment i s static i n the sense that the force pattern with

reference to the subject i s unchanging at constant velocity and is

supernormal in magnitude.

In Figure 3a the subject i s seated in a closed lighted room on

a human centrifuge and facing in the direction of rotation. When

exposed to a centripetal force of 1 .O g unit, h e perceives the room

196
a s sloped with down on his right side. When visual cues are greatly

reduced (Figure 3b), the slope increases, and there may be good

concordance between the visual and force upright. This orientation

of the subject creates a more favorable opportunity for him to indicate

horizontality by clockwise o r counterclockwise rotation of Q visual

target or rod than when he faces the center where estimates would

be made as deviations above or below a n imaginary horizon.

-- ---
of Nonvisual Cues on the
Examples of the Influence -

--
Visually Perceived Direction of Space

A large body of information has been obtained by having subjects set a

visual target or rod in a n otherwise uniform visual field either to internal

or external spatial coordinates (5-9). Many investigators since Aubert

(10) have explored the effects of tilting their subjects in the gravitational

field, and with the introduction of the human centrifuge (1 1, 12) it

became possible to change the direction of the gravitoinertial fore3

vector with respect to the subject. There a r e interesting and important

differences between the responses obtained with tilt and on the centrifuge,

not all of which have been satisfactorily explained.

THE OCULOGRAVIC I LLUSlO N

In Figure 4 a subject is shown seated facing the direction of

rotation while exposed to a centripetal force of 1 .O g unit (13). The


sketch depicts the arrangement of physical objects as viewed by

closed circuit television. Note the free swinging plumb bob

which i s the only indication of the gravitoinertial vertical.

Figure 5 shows how a naive subject perceives the situation with

eyes closed; he feels as i f he i s tilted to the right i n an upright

room. A sophisticated subject i s also aware of the tilt but w i l l

realize his position has not changed with reference to the room.

Both subjects, i f viewing a luminous line i n the dark while suddenly

subjected to a centripetal force of 1 .O g unit, would perceive the

line as rotating slowly clockwise from the horizontal position through

an arc usually greater than 45'. This i s an illusory or apparent motion

representing influences of cues from the force environment on visual

spatial localization. If the subject is requested to set the line to the

Earth horizontal, he rotates i t counterclockwise from i t s original setting

toward the gravitoinertial horizontal, usually overcompensating at this

level of force; grasping a swivel rod with eyes closed, he also sets

this near the gravitoinertial horizontal. The results are scored i n

terms of correspondence of the settings to the gravitoinertial horizontal .


With the visual target the threshold* of perception for perceiving the I

"75 per cent (or greater) correct responses


illusory rotation with the subject upright i s 1 .OW3 g units, about

equivalent to a n angle phi of i .5O (14).

The settings by normal subjects and by persons with bilateral

labyrinthine defects (L-D subiects) (13) who were requested to

maintain the line at the horizontal continuously throughout a n

experimental trial in which they were subjected to a change in

direction of gravitoinertial force of about 20° are shown in Figure 6.

Note the delay or lag between the change in force vector and the

apparent rotation of the line, indicating, presumably, the complex

nature of this integrative mechanism (15).

The effects of having the subject delay in opening his eyes a r e

shown in Figure 7. This demonstrates that visual perception is not

essential for the integrative action, although it tends to favor it

slightly. Vision is essential only to display the effects.

n Figure 8 is shown a comparison between the settings of naive

normal and L-D subjects exposed to gravi toinertial forces corresponding


to deviations from the gravitational vertical (cngle phi) of loo, 20°,
30°, and 40° (13). The variance was great in the case of the ten

L-Ds, but not in the normal subjects. The group differences were

attributed to the presence and absence of vestibular, and more likely

otolith, function.

199
The L-D subjects over a period of time demonstrated

improvement" i n the correspondence of their settings with the


II.

gravitoinertial horizontal. I n addition to a possible practice

effect, although the means of monitoring was not evident, the

settings were greatly improved with prolonged exposure (16) and

by encasing the subjects in Fiberglas molds. Some of these factors

were evident i n the experimental findings upon comparing the

settings of the luminous line between normal and L-D subjects

when exposed to identical changes in the gravitoinertial upright,

once when submerged to the neck, and again under dry conditions (17).

In the latter circumstance the use of Fiberglas molds tended to

maximize the area of good contact with the centrifuge while under

water these contacts were minimal.

The curves in Figure 9 summarize the findings. Three normal subjects

manifested little difference i n setting the line to the gravitoinertial

horizontal under dry and wet conditions. On the other hand, the L-D

subjects manifested a great difference; submerged they set the line very

close to the Earth horizontal which coincided closely with their internal

horizontal coordinate; when dry, the settings were qualitatively similar

but quantitatively about half the value indicated by the normal subjects.
Put in other terms, the loss of cues from the receptor organs

responding to mechanical force had only a slight effect in the

normal subjects inasmuch as the distance receptors in the otolith

organs were functioning normally; the quantitatively slight

decrease might be said to represent the contribution of the non-

otolith receptors under dry conditions. The L-D subjects under

dry and favorable conditions demonstrated that the nonotolith

receptor organs provided good cues to the force environment

despite the absence of distance receptors, and their settings were

a measure of these cues alone. Underwater, the cues were greatly

diminished, and in the absence of distance receptors there was

shown fo be little influence from gravitoinertial cues.

- - -
Certain Effects of Lateral Tilt in the Gravitational and
,a?-,- I__ I -
Gravitoinertial Fields

Seated upright in a tilt chair normal subjects set a luminous line

approximately to the gravitational horizontal but manifest a

characteristic bias as they are tilted leftward or rightward through

90°. Initial ty, the bias appears as an over- and later as a n under-

compensation termed, respectively, the E- and A-phenomenon, as

201
shown in Figure 10 (18). The bias i s greater and the consistency

less i n L-D subjects.

This bias as a function of increasing G load was measured on

the centrifuge by controlling the deviation of a freely swinging

platform from the gravitoinertial upright (19). In Figure 11 the

family of curves obtained from eight normal subjects shows the

increase i n bias with increasing magnitude of force, and i n

Figure 12 are the findings under similar conditions i n two subjects

without vestibular function. Note that the change from the E- to

A-phenomenon occurs with smaller angles of t i l t i n L-D subjects

compared with normal subjects and that the bias tends to be greater

and the variance i n the settings far greater.

When fixating the luminous line while lying on the side as depicted

i n Figure 13 not only i s the A-phenomenon prominent but also, for

some subjects, the line appears slowly to rotate clockwise and counter-

clockwise, a form of apparent motion (20). The estimations of a

Mercury astronaut, of a normal, and of an L-D subject are shown in

Figure 14 (21). The estimations of the astronaut were typical for two

subjects while those of the normal and L-D subjects represented the

modes for both groups who manifested great individual variance.


These findings indicate that the best concordance between

nonvisual and visual cues to the gravitational vertical is provided

with man upright or nearly upright. Presumably this is the result

of much practice with excellent monitoring possibilities. A

constancy bias with regard to nonvisual cues can be demonstrated

with increasing angles of tilt and with increasing g load for the

same angle of tilt in normal persons. To persons without vestibular

(otolith) function the bias and its variance a r e greater, and under

gravitational conditions the angle at which E to A reversal occurs


is smaller than in normals.

Insofar as these findings may be extrapolated to weightlessness,

it would appear that agravic touch, pressure, and kinesthetic cues

representing an unusual pattern would increase the tendency toward

bias while lifting the g load would reduce it. The poverty of cues

from the several sensory systems is summarized in Table I .

Important questions were whether a person in weightlessness

would perceive a line of light in the dark as stationary with respect

to clockwise or counterclockwise rotation, and how readily it would

be influenced by agravic touch, pressure, and kinesthetic cues. It

was with these considerations in mind that we suggested the

experiment now to be described.


THE IN-FLIGHT EXPERIMENT

Me thodo logy

Subjects. The medical findings on the four astronauts who

participated in GT V and VI1 flights are available elsewhere in

NASA publications

Equipment. The goggle device used represented a modification

and miniaturization of a target-device previously described (22). It

consisted essentially of a collimated line of light in an otherwise

dark field. This "line" could be rotated about its center by means

of a knurled knob. A digital readout of "line" position was easily

seen and was accurate within 0.25O.

The goggle device was monocular and fabricated in duplicate

so that the astronaut in the lefthand seat used the right eye with

the readout visible to the astronaut on his right, and vice versa.

The readout was adjusted for each flight so that the instrument's

zero was represented by a value other than zero or 180° to

eliminate or reduce the possible influence of knowledge of the

settings upon subsequent judgments. Horizontality with respect to

the apparatus was 6 1 . 3 O for the astronaut on the left and 98.8O

for the astronaut on the right in the Gemini V, and 76.6O and

101.6' for the left and right Gemini VI1 astronauts.


It was necessary to incorporate the device with the Vision Tester

which wds used i n another experiment (Figure 15). The device was

held at the proper position, with the lines of sight coincident with

the optic axes of the instrument, by means of a bite-board individually

fitted to the subject. A head brace, as shown in Figure 15, was

provided to connect the bite-board of the instrument to the map

board slot of the spacecraft and thereby eliminate any rolling move-

ment or displacement of the zero target setting for horizontal with

respect to the spacecraft; a limited amount of freedom around its

pitch axis was permitted by the folding configuration of the brace as

designed for storage purpmes. This method of fixing the Vision Tester

to the spacecraft was not used i n the GT V mission, but a similar

positioning of the instrument was achieved by having the subject s i t

erect in his seat with his head aligned with the head rest.

Procedure. The preLflight testing of the Gemini V crew was

accomplished sixteen days prior to their flight. The Gemini VI1

crew were similarly tested on two different occasions, nineteen

and six weeks prior to their flight.


Pre- and post-flight, the measurements were made with the

subject rigidly secured i n the upright position. The experimenter

offset the line clockwise or counterclockwise i n variable amounts,

then the subject set i t to what he regarded as vertical. This was

repeated five or more times.

The method in-flight was as follows; Immediately after

completion of the Visual Acuity Experiment, and without removing

the instrument from his face, the subject prepared for making his

judgments of horizontality by occluding the left eyepiece and

turning on the luminous target before the opposite eye. The target

appeared against a completely dark background. The observer

astronaut offset the line, and the subiect's task was to set i t parallel

t o an element of the spacecraft panel horizontal with respect to

himself. When satisfied with the setting, he closed his eyes and

removed his hand from the knurled knob. This served as a signal

to the observer to record the setting and offset the target. This

procedure was scheduled to be repeated five times during each

of the daily test sessions. In the interest of conserving vital

spacecraft power during the early part of the Gemini V flight, no

settings were made; for the same reason during revolution 24, 39,

206
and 54 only one judgment of horizontality was made by each

subject. Upon completion of a test session by the first subject

the Vision Tester was handed to the other pilot, and the same sequence

was carried out after completion of the visual acuity test. Finally,

the readings for each pilot were tape-recorded by voice.

RESULTS

In Figure 16 i s shown the measurements obtained i n GT V. The

striking feature i s the difference i n estimations of horizontality i n

the case of Pilot A obtained in-flight as compared with pre- and

post-flight . Post-flight variance was significantly greater than the

variances for each of the in-flight measurement groups and was also

significantly greater than pre-flight variance. The estimates of

Pi lot B revealed no systematic differences except that the post-flight

variance was greater than pre-flight .


The findings obtained on the two astronauts in GT VI1 are shown

i n Figure 17. For Pilot C there i s no systematic variance differences

among the pre-, eost- and in-flight measurement. For Pilot 0

variance of pre-f light measurements was significantly greater than

variances for a l l other sets of measurements including post-flight.

Post-f light variance was significantly greater than the variances


of in-flight measurement and for 9 of the 14 sets of measurements obtained

during orbital flight.

Two findings deserve further comment, namely, the small intra-

test variance in a single series of inflight settings and the apparent

bias manifested by astronaut A.

The finding that the intratest variance of in-flight settings never

exceeded and often was smaller than the pre- and post-flight settings

becomes even more significant when account is taken of the unfavorable

conditions aloft, especially in GT V, where it was not feasible to use

a "biting board." It is a safe prediction that if the in-flight settings

had been made under terrestrial gravitational conditions, the intratest

variance would have been far greater than pre-flight and probably

greater than post-f light measurements aboard the carrier.

As pointed out above, in attempting to anticipate the influence

of agravic cues on spatial localization the loss of G loading might

be expected, by extrapolation, to reduce the tendency toward a

bias while t h e unusual patterning of sensory cues, especially in the

absence of otolith function, might tend to increase this tendency.

The small intra- and inter-teg variance in setting the line during

exposure to weightlessness strongly suggests that cgrcvic cues exert

a weak influence on central intergravi tational processes underlying


visual spatial localization, Stated i n another way, the loss of sensory

information from the otolith organs and other receptor organs stimulated

by gravity following transition into weightlessness did not appear to

influence visual mechanisms concerned with the perceived direction

of space. Under these circumstances the sensory information i s so

meager and the pattern so unusual that i t would hardly serve as adequate

primitive sense experience out of which to construct a concept of

physical space. Once this concept has been established, however,

meager postural cues may suffice for spatial orientation even i n

darkness.

These findings have important implications for the interpretation

of ground-based experiments using essentially the same procedure.

They strongly suggest that the A- and E-phenomena and their variants

and the oculogravic illusion and i t s variants are the positive results

of sensory inputs and that the differences observed between normal

and L-D subjects imply either a greater or modulating influence or

both. Lifting the gravitational load did not lead to rotary autokinesis,

for example, implying, i n turn, possible influences via the extra-

ocular muscles .
The question arises whether the in-flight settings would have

revealed less variance i f the astronauts' task had involved setting

the line to the horizontal body coordinate representing personal

space rather than to an external reference. Although this question

cannot be answered, i t would seem that the variance might have

been less inasmuch as setting the line to an external reference

involved an extra step dependent on memory of the relation betwen

the two frames of reference.

With regard to the in-flight settings of astronaut A, they differed

from those of the other three i n that they were approximately 300

clockwise with respect to the external horizontal reference but were

similar in that the intra- and inter-trial variance were small. The

question arises whether the settings near 30° represent a systematic

procedural error? a bias, or settings with reference to independent

symbolic cues. The same goggle device was used post-flight; hence,

a mechanical error is ruled out. Inasmuch as the task involved

setting the line to a horizontal cabin reference coinciding with the

astronaut's body horizontal, it did not matter if the body reference

210
was chosen, thereby eliminating any confusion between the two,

Our experience is so limited that we cannot even answer the

question whether a bias of this magnitude based on nonvisual

sensory inputs under agravic conditions is possible The

phetmmenon does not seem typical of the characteristics of biases

manifested under terrestrial conditions, but this does not rule out

the possibi l i t y . This can of course be put to the test whenever


i t becomes feasible i n weightlessness to manipulate sensory cues

and investigate the effects on spatial localization. There is too

the possibility that the settings were made using a cue other than

the internal coordinates of the body. This of course can be

controlled i n the future.


subject's head with respect to the tilt device. This method has been

used i n parabolic flight, and some of the findings are depicted i n

Figures 19 and 20,

I t would have been of interest to determine any changes in roll as

a firnction of exposure aloft i n the Gemini flight, but for obvious

reasons thio was out of the question, Measurements were made, however,

pre- and post-flight,

APPARATUS AND PROCEDURE

The apparatus used for measuring ocular counterrolling i s essentially

a tilt device on which a camera system i s mounted (25), The main

supporting part of this device acts as a carrier for the stretcher-like

section, This section contains Velcro straps and a saddle mount to secure

the subject i n a standing position within the device and can be rotated

+ o
laterally to -90 about the optic axis of the camera system and, when

the subject Os pro rly adjusted, a ut the visual axis of his right

d was also used i n counterroll!

~ e s t ~ ntog fix the subj ith respect to the camera reco

system,

The camera system use h the natural irls landmarks

includes a motor driven 35 mm camera with bellows extension an

electronic flash unit (25). A console located at the

device contains a cks which supply the electronic

212
flash, a timer control mechanism, and controls for the flashing, round-

fixation light which surrounds the camera lens. A triaxial accelerometer

unit which senses and relays signals of linear acceleration to a Consolidated

Electrodynamics Corporation galvonometer recorder was mounted to the

head portion of the device for shipboard use.

A test cubicle 12' x 16' x 10' insulated against outside sounds, light,

and temperature was constructed for carrying out the post-flight tests

of spatial localization and counterrol ling onboard the recovery carrier.

Immediately prior to the pre- and post-flight testing one drop of

1% pilocarpine hydrochloride ophthalmic solution was instilled i n the

subject's eye which was opposite to the one he used for making visual

orientation judgments. These judgments were made first. Then the

subject remained i n the upright position i n the tilt device, the Vision

Tester and i t s bite-board were removed, and preparations were made for

photographicall'y recording the eye position associated with a given

position of body tilt. The counterrolling bite-board was inserted i n the

subject's mouth, and the position of his appropriate eye was adjusted so

that it coincided with the optic axis of the camera system when he fixated

the center of the flashing red ring of light, Six photographic recordings

were made at this position; then the subject was slowly tilted i n his

lateral plane to each o f four other positions 6250, 5509, apld the Same
photographic procedure was repeated

213
o f g loading, which should tend to reduce it. Although one astronaut

consistently set the line approximately 30 degrees from the external

reference while in-flight, it remains to be verified whether these

settings represented the internal (body) reference, which, under the

experimental conditions, should have been the case

Stated differently, the results demonstrate the possibility of

investigating the influence, i f any, of agravic sensory information on

perceived spatial visual localization.

I f our conclusion i s correct that the influence of agravic cues on

visually perceived direction i n space i s small, this influence should

be even less discernable when visual cues are present. Thus, i n

weightlessness the interaction between visual and non-visual cues

should favor the former to a greater degree than under terrestrial

conditions

214
OTOLITH FUNCTION AS ~ E T E ~ I ~ ~ Q

BY OCULAR COUNTERROLLING

Direct testing of the function of the otolith organs as in the case

of the semicircular canals, vision or hearing i s not done routinely because

of the great difficulties involved and the limited clinical interest in these

organs, The difficulties include manipulating the physiological stimulus

and lack of a specific, accurate indicator. Among the methods used,

estinwtion of the oculogravic illusion with the subject submerged to reduce

nonotolith sensory inputs and ocular counterrolling with head fixed to reduce

influences from 'kwvical reflexes" a r e in all likelihood the most accurate.

Only the latter i s pmctical, and the most accurate measurements of the

roll or ocular torsion have been made using "landmarks" in the fundus (23)

or artificial or natural external markings (1). In Figure 18 Is shown the

change in position of the eye as a function of lateral tilt from the upright;

the measurements were made from photographs of the face o

upright and tilt positions (2 l ~ a b ~ l of


~ tthe
y method was e s ~ a ~ l ; s h

subjects. Moreover, when these same subjects were

exposed to changes in direction and ~ g n i t u d of


e force on a h u m n

cenirifuge, the amount of the roll in the nor

a function of the l a t e r a ~ l y ~ a c t ~(sn g

a photographic procedure which depends on tching crypts in the iris

between photographs taken with the subject upright and in lateral ~ i (25)
l ~

inates the need for sutures but requires absolute


The accelerometer system was used post-flight during a l l testing

to continuously record motions of the recovery ship around i t s roll,

pitch, and yaw axes.

Post-flight examinations were begun for pilots A, B, C, D,

approximately six, five, six, and four and one-half hours,

rsspectively, following their recovery at sea.

RESULTS

The counterrolling measurements are summarized i n Figures 21

and 22. The values for pilots A and B were i n the lower range of a

large random group of normal persons while the values for pilots C

and D were i n the mid-range. No significant differences were found

pre- and post-flight i n any of the four astronauts. The slight

difference i n the counterroiling curves can be accounted for by the

small rotary oscillations (physiological unrest) of the eye cnd the fact

that an average of several recordings is used to define the position of

the eyes associated with any given body tilt.

216
DISCUSS1ON

The failure to find any significant changes was not unexpected but

i t remained to be done, The only feature worthy o f comment i s the

relatively small roll in the case o f astronauts A and B. Inquiry has not

disclosed any common factor associated with the flight which might

account for the findings,

SUMMARY AND CONCLUSIONS

Two experimental probes were carried out involving the astronauts

in the Gemini V and VI1 flights.

One was concerned with the influence o f nonvisual cues on spatial

localization, The astronauts' task was to set a dim line of light in an

otherwise dark field to an external horizontal reference; the Earth's

horizontal was used pre- and post-flight and an element i n the spacecraft,

horizontal with respect to the astronaut, was used in-flight.

The second experiment consisted i n the pre- and post-flight

measurement of ocular counterrolling which depended, for the greater

part at least, on a reflex response having i t s genesis in the otolith appmtusa

No significant pre- and post-flight differences i n response were demonstrated

The outstanding finding was the small intratest variance i n the

settings made in-flight and relatively small bias in three of the four

astronauts, These results suggested that the unusual patterning o f tactile

cues, which would tend to induce a bias, was more than offset by the loss
ACKNOWLEDGMENTS

We are extremely pleased to acknowledge the support of

the Cffice of Advanced Research and Technology (Biotechnology

and Human Research) i n obtaining ground-based data which

provided important background information for the in-flight

experiments. We are grateful to the Manned Spacecraft Center

for extending us the remarkable opportunity together with the

necessary support for conducting vestibular experiments i n

conjunction with the Gemini V and VI1 manned space flights.

The success of these experiments was i n large part dependent upon

the subjects involved, astronauts Frank brman, Charles Conrad,

Gordon Cooper, and James Love1I. These men deserve special

commendation for their extraordinary effort i n gathering these

research data under the considerable constraints necessarily imposed

i n these’historical events.

218
REFERENCES

1 , Graybiel, A,, and Woellner, R. C., A new and obit-stive method

for measuring ocular torsion, --


Amer. J . Ophthal .,-
47~349-352,

1959.

2, Graybiel ,A,, The effect on vision produced by stimulation of the

semicircular canals by angular acceleration and stimulation of

the otolith organs by linear acceleration. In: White, C , S o


-3
,
and knson, 0. O,,Jr. (Eds,), Physics and Medicine of the

Upper Atmosphere, Albuquerque, NoM,: University of New

Mexico Press, 1952 Pp 494-508.

-
3. Graybiel, A., Oculogravic illusion, Arch, Ophthal., -
48:'605-615,

4. Vinacke, W. E., Illusions experienced by aircraft pilots while flying,

-J ,aviat . - -
Med,,18:308-325, 1947,

,Uber das Aubertsche Pknomen. -Z,


II
5. MClller, G o E. Sinnesphysiol,,

6. Witkin, H, A. , Perception of the upright when the direction of the


--
force acting on the body i s changed, J expo Psychof ,,-
40:93-

106, 1950,

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7, Teuber, H,, Perception, In: Field, Jo, Magoun, Ho Wo, and

Hall, V. E. (Eds.), -
Handbook of Physiology. Section I , -
--
Neurophysiology. Vol. 111 , Washington, D o C,: American

Physiological Society, 1960, Pp 1595-1668.


8. Whiteside, T. C, Do,Graybiel, A,, and Niven, J . I., Visual

illusions of movement. - - 88:193-210,


Brain, 1965.

9. Correia, M. J,, Hixson, W. Go, and Niven, J. I . , Otolith shear


and the visual perception of force direction: Discrepancies

and a proposed resolution. NAMl-951 , NASA R-93. Pensacola,

Fla.: Naval Aerospace Medical institute, 1965,

10. Aubert, H., Eine scheinbare bedeutende Drehung van, Objekten bei

Neigung des Kopfes nach rechts d e r links. Arch. path. Anat,


- I -

physiol .,
g:381-393, 1861 ,

11. Purkinje, J .:,


Beitrage zur niiheren Kenntnis des Schwindels aus

Heautognostischen DaDen. Med. Jb. _I_-


,--
Wien, 6:79-125, 1820.

12. Mach, E., Grundlinien der Lehre von den Bewegungsempfindungen.

Leipzig: Wilhelm Engelmann, 1875.

13. Graybiel, A., and Clark, B., Validity of the oculogravic illusion

as a specific indicator of otolith function. Aerospace Med.,-


36:1174-1181,
_I 1965.

14. Graybiel, A., and Patterson, J. L., Jr., Thresholds of stimulation

of the otolith organs as indicated by the oculogravic illusion.

.
J- -appl , Physiol ,,7:666-670, 1955.

15. Graybiel, A,, and Brown, R. H, The delay in visual reorientation

following exposure to a change i n direction of resultant force

--
on a human centrifuge. J, gen, Psychol., 45:143-150, - 1951 .

220
I60 Clark, Bo ,and Graybiel ,A, ,Contributing facton in the perception
of the oculogravic illusion, - - J, Psycho10,76:18-27,
Amer, 1963,

17. Graybiel, A, ,Miller, E, F. ,I I , Newsom, 80 Do, and Kennedy,

R, S o ,The effect of water immersion upon the oculogravic

illusion in normal and labyrinthinedefective subiects. To be

publi shed,

18, Miller, E, F., I I , Fregly, A, R., van den Brink, Go, and Graybiel,

A,, Visual localization of the horizontal as a function of body

filt up to f 900 from gravitatF,onaI vertical , NSm\-942,

R-47, Pensac-ola, Fla,: Naval Sch6ol of Aviation Medicine,

1965,

19, Miller, E , F. ,! I , and Graybiel ,A, ,Magnitude of gmvitoinertial


force, an independent variable i n egocentric visual localization

J ,-
of the horizontal e - expo Psychol Of-
71 :452-460, 1966.

20, Miller, E, F,, I I ,and Graybiel, A., Rotary autokinesis and

displacement of the visual horizontal associated with head

- -
(body) position, Aerospace Nied., 34:915-919, 1963.

21, Miller, E, Fa, I!, and Graybiel, Ao, l e of the otolith organs in

the perception of horizontalP l y .--


Amer. J , Psychol .,-79:24-37,
1966.

22. Clark, B o , and Graybid ,A. ,A device to manipulate and to indicate


the position of remote test-obiects. --
Amer. J Psychol ., -
65:286-
287, 1952.
23. Opfer, Po H,, Untersuchungen Uber die Raddrehung der Augen

beim Normalen, gemessen am Augenhintergunde nach Gmhe .


Arch. Ohr,-Nas,-KehlkHeiIk, , 136:298-313,
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24, Woellner, R, Go, and Graybiei, A,, Counterrolling of the eyes and

i t s dependence on the magnitude o f grbvitational or inertial

force acting laterally on the body, J a appl ,. Physiol


- - ,,
_14632-634, 1959,
I

25, Miller, E, Fa, ! I , Counterrolling of the human eyes produced by

head tilt with respect to gravity, -


Acta otolaryng., Stockh,,

54:479-501 ,1 962.
-

222
TABLE LEGEND

1 ,. Contribution to the perception o f extrapersonal space of various

sensory cues derived from natural and weightless conditions.

223
C

224
FIGURE LEGENDS

Figure 1 - Extrapersonal Space


Figure 2 - Interaction Between Cues From Visual and Gravitoinertial
Force Environments.

Figure 3 - Depicting the Illusory T i l t of a Physically Upright Room

Perceived by a Subject on a Human Centrifvge.

Figure 4 - Physical conditions as perceived by closed circuit television

with subject fixed during exposure on human centrifuge. Plumb bob only

indication of change.

Figure 5 - Naive subject facing away from direction of rotation fixating

a luminous line i n the dark regards himself as tilted in an upright room.

Figure 6 - Change in setting of star os function of time compared with

change in direction of resultant force of 20'. Curves depict mean values,

Figure 7 - Mean values for the oculogravic illusion in five normal subjects

with progressively longer delay time i n presenting the target.

Figure 8 - Estimates of the oculogravic illusion by normal and L-D subjects.


Single settings of star.

Figure 9 - Change i n direction of gravitoinertial vertical with respect to

subject (Angle Phi).

Figure IO - Mean curves represent E & A phenomena of individual test


sessions of one subject .
Figure 11 - Change i n E-phenomenon as a function of increasing G level i n

normal subjects.
Figure 12 - Change in E- and A-phenomena as a function of increasing
G level in L-D subjects.

Figure 13 - Diagram of apparatus used to determine location of visual


horizontal with subject in upright or recumbent position

Figure 14 - Localization of a dim line of light in the dark to the


horizontal by three subjects lying on their left side.

Figure 15 - Photograph illustrating the Vision Tester and i t s use within


the spacecraft. Note head brace connecting the biteboard of the

Vision Tester to the instrument panel.

Figure 16 - Estimations of visual horizontality ,made by crew of


Gemini V pre-, in-, and post-flight.

Figure 17 - Estimations of visual horizontality made by crew of


Gemini VI1 pre-, in-, and post-flight.

Figure 18 - a) Showing sutures i n conjunctiva and markers at outer


canthi; b) Demonstrating counterroll of eye with lateral tilt.

Figure 19 - Counterrolling as a function of magnitude of gravitational


force (Zero 6, 1/2 G, 1 G) and body position with respect to direction

of force i n normal and labyrinthine-defective subjects.

Figure 20 - Relative otolith activity (mean counterrolling response of


three subiects) as a function of the logarithm of the gravitational stimulus.

226
Figure 21 - Ocular counterroiling measurements of the Gemini V crew
obtained pre- and post-flight.

Figure 22 - Ocular counterrolling measurements of the Gemini VI1


crew obtained pre- and post-flight.
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MEAN VALUES FOR THE OCULOGRAVIC ILLUSION IN FIVE NORMAL SUBJECTS
WITH PROGRESSIVELY LONGER DELAY TIME IN PRESENTING THE TARGET

“t

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Tlme of rotation In seconds

CONTINUOUS SETTINGS, NORMAL SUBJECTS


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236
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SUMLURY AND CONCLUSIONS CONCERNING MEDICAL
RESULTS OF THE GEMINI V I 1 MANNED SPACE F L I G H T

C h a r l e s A. B e r r y , M. D.
D i r e c t o r of M e d i c a l R e s e a r c h and O p e r a t i o n s
NASA M a n n e d Spacecraft C e n t e r
Houston, Texas

/
i
SUMMARY AND CONCLUSIONS CONCERNING MEDICAL
RESULTS OF TEE GEMINI VI1 M A W D SPACE FLIGHT

In summation, I think it is quite obvious that


there are two principal tasks we must accomplish if
we are to evaluate man's response to the space en-
vironment. The first task requires realistic
answers to the questions of whether it is safe to
expose man to the environment anticipated and if
so, a determination of how long you can expose
him without encountering significant physiological
or performance decrements. The second task relates
more closely to the previous discussion. It requires
a search for the causes of some of the changes which
have been seen and an attempt to learn more about
man's basic system functions in the space environ-
ment. In accomplishing these tasks, we have used
a rather false separation into what might be called
operational tasks and those that could be called
experimental tasks.
I think you are all well aware of our medical
position prior to Gemini. There were many predic-
tions about what man could and could not do and in-
deed many people felt that man was the limiting
factor as far as our space activities were concerned.
Our primary job then became one of obtaining infor-
mation enabling us to commit man to longer periods
of time in the space environment. Our immediate
goal was to qualify him if possible for the lunar
mission.
The operational activities accomplished in
attaining this goal have included routine pre-
and postflight medical studies consisting of phys-
ical examination, blood, urine, and x-rays studies,
supplemented by inflight observations made by real-
time physiological monitoring and adequate re-
porting of the crews inflight. Additional crit-
ical information was obtained from debriefing the
crews postflight. The purpose of all of these
activities was to secure information allowing us
to assess the physical and mental status of the
crew and their capability to perform their partic-
ular mission. I would like to summarize some of
the data obtained from these operationa medical
activities.
The tilts have been previously discussed by
Dr. Dietlein. A comparison of pre- and postflight
t i l t s has provided u s an assessment of t h e cardio-
v a s c u l a r response t o t h e t o t a l s p a c e f l i g h t environ-
ment. The t y p i c a l p o s t f l i g h t tilt response of in-
creased p u l s e r a t e and decreased blood p r e s s u r e
h a s been seen on each of our missions. Figure 1
summarizes t h e i n c r e a s e i n h e a r t r a t e during t h e
tilt from a comparison of t h e p r e f l i g h t w i t h t h e

f i r s t p o s t f l i g h t and second p o s t f l i g h t tilts.


The percentage i n c r e a s e i n h e a r t r a t e appears t o
i n c r e a s e i n v i r t u a l l y a l i n e a r f a s h i o n through
t h e eight-day f l i g h t and t h e t h e o r e t i c a l projec-
t i o n of t h i s curve t o 14 days caused some concern
p r i o r t o t h e 14-day f l i g h t . You w i l l n o t e t h a t t h e
14-day data are more l i k e t h e four-day d a t a . It

i s our f e e l i n g t h a t many f a c t o r s are involved i n

t h i s less s e v e r e response, some of them being t h e


t h r e e 10-minute exercise p e r i o d s p e r day, t h e
d i e t , t h e removal of t h e s u i t s f o r a c o n s i d e r a b l e

period of t i m e . and perhaps t h e longer period of


t i m e f o r adaption t o t h e s p a c e f l i g h t environment-
W e have noted a r e t u r n t o normal p r e f l i g h t v a l u e s

w i t h i n a 50-hour period r e g a r d l e s s of t h e d u r a t i o n

of t h e s p a c e f l i g h t . Some i n d i v i d u a l v a r i a t i o n w a s

seen and was expected- There w a s a near syncopal

253
affair in one instance following the 14-day flight
and one instance during a preflight tilt on an
earlier mission,
The next major group of observations conducted
as operational procedures involved the blood studies.
In addition to the normal Poutine of blood counts
pre- and postflight, blood volume studies were
conducted on the four- eight- and 14-day flights.
Figure 2 graphically represents the absolute neutro-
philia observed. It has returned to normal in
24 hours. Figure 3 summarizes the blood volume re-
sults obtained, the most noteworthy being a de-
crease in red blood cell mass which like the tilt
data appeared to be increasing through the eight-
day flight. We had expected to see most of the
change in plasma volume studied by the RISA tech-
nique. The data reveal a normal vascular or blood
volume maintained by an increase in plasma volume
of the 14-day flight. A decrease in red cell mass
is still noted, but it does not appear to increase
with increasing duration of flight. The RISA and
chromium-51 studies have not been done since the
14-day flight and we look to the Apollo flights
to provide additional data in this area. An

254
example of the Cr-51 data is seen in Figure 4.
Continued study of the red cells has shown that there
is an increased hemolysis noted postflight. This
may be seen graphically in the case of the command
pilot on the 14-day flight in Figure 5. This in-
creased tendency to hemolysis had disappeared by
48 hours postflight. The increased hemolysis has
also been demonstrated on flights as short as the
one day Gemini VI mission. It appears that we
have cells that are increased in size, more fra-
gile and thus easily destroyed by some mechanism
requiring further investigation. The routine count
and fragility determinations can be made on every
mission.
One of the important points I would like to
make is the flexibility we have retained by con-
ducting this procedure as an operationalone rather
than as a numbered experiment. When it was obvious
that we were obtaining some interesting data con-
cerning the red cell mass, our procedure was modi-
fied without a requirement for making large paper-
work changes in protocols and staffing them through
a number of channels. We did the modification in
a timely fashion in order to acquire the best

255
i n f o r m a t i o n possible and t a k e advantage of t h e
s i t u a t i o n as it arose.

W e p l a n t o c o n t i n u e t h e s t u d y of t h i s r e d c e l l

m a s s phenomenon i n chamber s t u d i e s i n t h e hopes


o f determining t h e mechanism. W e do f e e l t h a t

o u r 100% oxygen environment may be involved i n t h e


changes noted and, t h e r e f o r e , w e f e e l t h a t f u r t h e r
chamber work i s mandatory. An e a r l y r e p o r t from
t h e chamber s t u d y conducted a t t h e School of
Aerospace Medicine d u r i n g which w e had o u r p e o p l e
conduct t h e same blood s t u d y h a s r e v e a l e d some
d e c r e a s e i n t h e r e d c e l l mass, b u t a p p a r e n t l y n o t
of t h e s a m e magnitude n o t i c e d i n f l i g h t . W e are

unable a t t h e p r e s e n t t i m e t o s a y how long t h i s


decreased red c e l l mass p e r s i s t s p o s t f l i g h t . It

h a s been followed on o n l y one o c c a s i o n when t h e


d e t e r m i n a t i o n s w e r e r e p e a t e d on t h e 1 8 t h p o s t f l i g h t
day a f t e r t h e 14-day mission. A t that time, the
blood volume had r e t u r n e d t o n o m a 1 a s had t h e
plasma volume and r e d c e l l m a s s . W e are unable t o

s t a t e how long b e f o r e t h e 1 8 t h day t h e y had re-


t u r n e d t o normal.
B i c y c y l e ergometry w a s accomplished as an oper-
a t i o n a l procedure pre- and p o s t f l i g h t on t h e Gemini VI1
mission. Previous investigations have shown that
cardiovascular and respiratory functions are not
optimal when a heart rate of 180 beats per minute
is observed as a response to a gradually increased
work load. The bicycle ergometry was used as an
exercise capacity test pre- and postflight in order
to determine whether changes occur in crewmen's
physiologic reaction to work. The results on
Gemini VI1 were tentative only due to some equip-
ment problems. They appear to indicate a decrease
in exercise capacity and a reduction in oxygen
consumption. (See Figures 6 and 72
Though there was an experiment (M-5) which
required a number of biochemical determinations
on Gemini VII, we have routinely obtained some bio-
chemical measures on both blood and urine pre- and
postflight. No significant changes have been noted,
though the electrolyte and protein determinations
have been helpful in our assessment of dehydration.
Our routine physiological monitoring has given
us voluminous information on heart rate, both from
ground-based studies for comparison with flight
data and from the missions themselves. We have
noted peak heart rates at launch and re-entry on
each of our flights. (See Figure 8)
These i n c r e a s e d h e a r t r a t e s are t h e r e s u l t of
t h e t e n s i o n a t t h e s e two c r i t i c a l p e r i o d s and t h e

p h y s i o l o g i c response t o t h e i n c r e a s e d G l o a d s
encountered. The h e a r t r a t e d u r i n g o r b i t a l f l i g h t

h a s u s u a l l y settled a t an average r e s t i n g rate and

h a s shown adequate response t o any w o r k l o a d s


imposed. On t h e long d u r a t i o n missions, and i n
p a r t i c u l a r on Gemini V I I , w e w e r e impressed by t h e
f a c t t h a t t h e p l o t t i n g of high, mean, and low
h e a r t r a t e s (See F i g u r e s 9 and 10) allowed u s t o
f o l l o w t h e sleep s t a t e of t h e crewmen i n a v e r y
e f f e c t i v e manner. The p e r i o d s of waking c a n be
e a s i l y noted and our assessments of t h e t o t a l s l e e p
p e r i o d s i n t h i s manner matched f a i r l y a c c u r a t e l y
w i t h t h e reports of t h e c r e w and w i t h t h e d e t e r -
mination of sleep t i m e through t h e u s e of t h e EEG
on Gemini V I I ,
Blood p r e s s u r e s have been o b t a i n e d on a l l of
o u r missions through Gemini V I 1 and a t s e v e r a l c r i t -

i c a l p o i n t s d u r i n g t h e r e - e n t r y and landing a c t i v i t i e s
The p r e s s u r e s have been g e n e r a l l y w i t h i n what would
be considered a normal envelope and some peak pres-

s u r e s w e r e o b t a i n e d a t t h e t i m e of i n c r e a s e d h e a r t
rate due t o v a r i o u s stresses, (See F i g u r e 11)
W e have used a c r e w r e p o r t i n g system i n o r d e r

t o follow t h e i n t a k e of food and w a t e r during f l i g h t .


T h i s i s an important c r e w procedure if w e are t o
have any real-time assessment of t h i s physiologic
state. There are problems i n o b t a i n i n g a c c u r a t e
information of t h i s s o r t , because it r e q u i r e s
some meticulous o b s e r v a t i o n and recording on t h e
p a r t of t h e c r e w during very a c t i v e p o r t i o n s of
t h e mission. The w a t e r gun h a s a counter which
r e c o r d s a count f o r every half-ounce dispensed.
T h i s r e q u i r e s n o t i n g t h e gun reading p r i o r t o
o b t a i n i n g water, recording t h e r e a d i n g a t t h e con-
c l u s i o n , and s u b t r a c t i n g t o o b t a i n t h e d i f f e r e n c e
i n count, T h i s must t h e n be converted t o ounces

and recorded. There are obviously s e v e r a l p o s s i b l e


s o u r c e s of e r r o r i n such a method. W e have obtained

some most h e l p f u l information on t h e s t a t e of

h y d r a t i o n by t h i s method, however.
It would s e e m a p p r o p r i a t e t o look a t t h e med-

i c a l d a t a obtained t h u s f a r by e i t h e r o p e r a t i o n a l
o r experimental processes and t o assess t h e i r
i m p l i c a t i o n as f a r a s f u t u r e f l i g h t s are concerned.
This s o r t of a summay l e n d s i t s e l f t o t h e format
of a system review w i t h which physicians are f a m i l i a r .

259
-
SKIN
We have been concerned with the response of the
skin in a situation, where it has been moist a good
deal of the time and there has been only minimal
opportunity to do any sort of cleansing, We have
been very pleased with the capability of the skin
to maintain a state of normalcy even with the lack
of adequate hygiene which is present, We have
seen no infections and have had only minimal reac-
tion around sensor sites following 14 days of
flight. Following the eight-day flight, the crew
did have some drying of the skin which responded
to the use of a lotion. This same crew had some
difficulty with excess dandruff during the eight-
day mission.

THE CENTRAL NERVOUS SYSTEM


With the exception of the EEG used in only
one instance to evaluate the depth of sleep, our
best assessment of central nervous system function
comes from the overall crew response during these
missions. As we relate the ability of the crew to
to respond to the demands placed upon them, it is
obvious that the central nervous system must have
functioned in a very normal manner. They have

260
responded to many normal and emergency demands
through the various flight phases some of which
are summarized in Figure 12,

THE SPECIAL SENSES


Dr. Graybiel has discussed the results of the
vestibular experiment and in addition, we have
questioned the crew carefully following each
mission, including the Gemini IV eAtravehicular
activity. We have had no instance of disorienta-
tion during any of our flights and we have observed
no remarkable findings in this area,
Visual acuity has been measured preflight and
postflight without evidence of change. We have also
measured visual acuity inflight and have seen no
decrement caused by the weightless flight. We are
convinced that the pilot's reports of ground and
inflight findings are accurate.

EAR NOSE AND THROAT

We have had no change in hearing and no other


difficulties except for some drying of the nasal
mucous membranes and the throat. We feel that this
is related to our 10007 oxygen environment and such
findings have also been noted in some of our long-

261
term chamber studies,

THE CARDIOVASCULAR SYSTEM


Many of the findings in this area result from
operational procedures already discussed and in
summary we may say that the responses to massive
tilt are self-limited and return to normal within
a 5 0 hour period postflight, regardless of mission
duration through 14 days. We are not sure how
long a period is required for the blood volume
to return to normal, but we assume it to be a
matter of days.

THE RESPIRATORY SYSTEM I

We have seen no respiratory problems to date.

THE GASTROINTESTINAL SYSTEM


There has been no difficulty with ingestion of
food if it is properly packaged, nor have we seen
any difficulties with the passage of food through
the normally functioning gastrointestinal tract.
The use of the low residue diet, preflight and
inflight, has caused no difficulty,

262
THE GENITO-URINARY SYSTEM
W e have s e e n no a b n o r m a l i t i e s i n t h e f u n c t i o n

of t h i s system, e i t h e r i n f l i g h t or p o s t f l i g h t .
The h a n d l i n g of e i t h e r l i q u i d o r s o l i d w a s t e
s t i l l remains as a F o b l e m r e q u i r i n g f u r t h e r

effort.

THE MUSCULOSKELETAL SYSTEM

The x-ray d e n s i t o m e t r y and calcium b a l a n c e


s t u d i e s have been covered i n d e t a i l . I n summary,
w e may s t a t e t h a t w e are s e e i n g less evidence
of loss of muscle o r bone c o n s t i t u e n t s t h a n was

originally predicted. I t would appear a t t h i s t i m e

t h a t t h e changes noted are c e r t a i n l y w i t h i n an


a c c e p t a b l e range.

I n e v a l u a t i n g t h e response of man a s a system


t h u s f a r , it would appear t h a t h e h a s f u n c t i o n e d
i n a v e r y a c c e p t a b l e manner and h a s shown himself
t o be c a p a b l e of conducting prolonged missions
i n space. W e c e r t a i n l y expect t o see some physio-

l o g i c change b u t e x p e c t t h a t t h e changes noted w i l l


be w i t h i n t h e r a n g e s which w e have s e e n to date.

I n r e t r o s p e c t , our doubling of man's exposure h a s


been demonstrated t o be a n a c c e p t a b l e approach i n
o b t a i n i n g d a t a allowing u s t o commit man f o r
longer d u r a t i o n f l i g h t . Therefore, I feel t h a t
w e may c o n f i d e n t l y commit man t o a 30-day f l i g h t
i f he is given t h e proper environmental support.

I am s u r e t h a t w e are a l l aware of t h e adaptive

physiology being noted i n man's response t o t h e


flights. I t i s m o s t important t h a t w e document

t h e s e changes and e v a l u a t e them i n r e l a t i o n t o

t h e adaptation. W e must exert some e f f o r t t o

determine t h e mechanism involved. W e a r e seeing

man adapt t o a new environment c h a r a c t e r i z e d by


t h e zero-G s t a t e , and then readapt t o a 1-G en-
vironment h e r e on e a r t h . W e must study both of

these adaptations. The stress on t h e i n d i v i d u a l


i s of i n t e r e s t h e r e , f o r w e are asking him t o
adapt t o t h e w e i g h t l e s s s t a t e t o which h e is ex-
posed w i t h i n a s h o r t p e r i o d of t i m e ; and t h e n t o
do what appears t o be a more d i f f i c u l t a d a p t a t i o n
back t o t h e 1-G environment on e a r t h i n a period
of t i m e dependent upon f l i g h t d u r a t i o n ,
There are s o m e important p o i n t s I would l i k e

t o n o t e as a r e s u l t of t h e s e s t u d i e s . The f i r s t
is t h a t t h e conduct of an i n f l i g h t experiment is
a very d i f f i c u l t f i e l d o p e r a t i o n and t h i s i s par-
t i c u l a r l y t r u e i n t h e medical area. I think

264
there is no better example of this than the M-7
Calcium Balance Experiment. This is a difficult
task in isolated patients. In the case of these
missions, we are asking investigators to conduct
these studies in an operational situation which
is not in any sense like the hospital laboratory.
There are a number of complicated operational in-
terfaces and many of these cannot be rigidly
structured because they vary with the mission de-
mands. It is necessary to carefully select the
flight upon which we are to do any given medical
experiment. In other words, you cannot arbitrarily
state that we would like to run a calcium study,
for instance, and place it on the nearest avail-
able flight. The flight program must be care-
fully evaluated and the experiments which are to
be done must be integrated with a number of oper-
ational procedures. There are many of these ac-
tivities which may conflict with each other if they
are not properly programmed.
The second point relates to the need to have
some operational flexibility in conducting an assess-
ment of man's responses through operational measures
rather than necessarily by the laborious experiment
route. Many of the things that have b
medical experiments are not experiments at all;
but are merely measures of a particular function
of a body system. You could put a number of these
together and say that you have one large experi-
ment. For instance, the large nwnber of studies
which have been conducted on the cardiovascular
system are indeed a series of measures which,
when put together, could be called an experiment
or at least an evaluation of the cardiovascular
system.
We are tasked with the job of determining man's
response to the space flight environment and it is
an ongoing process which is planned for each flight,
no matter what its duration. We must record even
the minimal changes noted, evaluate their effect
upon the flight, establish an adequate hypothesis
concerning these effects, and hopefully establish
a system of measurement which will allow us to
elucidate the mechanisms involved. Our future
flight programs rely upon basic missions whose
duration is as long as our longest mission to date.
We must continue our evaluation of man if we are to
properly support this flight program,

266
We are dealing with very small numbers of people,
and we find that we must make sweeping conclusions
from very little information at the present time.
I think, however, that in viewing the overall
situation, we can all take pride in the fact that
there has been a large amount of medical infor-
mation obtained by working in a difficult space
'I laboratory .
I'
SUMMARY AND CONCLUSIONS CONCERNING MEDICAL
RESULTS OF THE GEMINI V I 1 MANNED SPACE F L I G H T

Figure 1 - NASA-S-66-11665 H e a r t R a t e T i l t Response Compared


w i t h Mission D u r a t i o n
Figure 2 - 66-11534 G e m i n i P i l o t s ' White B l o o d C e l l
Response

Figure 3 - 66-1715 G e m i n i B l o o d Volume Studies

Figure 4 - 65-8969 G e m i n i V B l o o d Volume D e t e r m i n a t i o n s


(Command P i l o t )

Figure 5 - 66-1140 H e m o l y s i s - G e m i n i V I 1 (Command P i l o t )

Figure 6 - 66-5463 G e m i n i V I 1 Ergometry S t u d i e s


(Borman)

Figure 7 - 66-5464 G e m i n i V I 1 Ergometry S t u d i e s


(Love11)

Figure 8 - 66-11663 G e m i n i Peak H e a r t R a t e s , Beats/Min

Figure 9 - 66-1765 Pilot Heart Rate - 4 hour i n t e r v a l s

Figure 10 - 65- 125 99A Pilot Heart Rate - 4 hour i n t e r v a l s


(Continued)

Figure 11 - 65-12592A G e m i n i V I 1 Command P i l o t B l o o d Pressure

F i g u r e 12 - 66-5820 E v i d e n c e of N o r m a l C e n t r a l N e r v o u s
System Function

268
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279
S o Po Vinagrsd, M.D.
Director, Medical Science and lCechnology
RASA Headquarters

281
The operational objective of the Medical Experiments Prograpp
looks w e l l beyond the Apollo missions t o prognosticate, vali-
date, and protect man's w e l f a r e on very long duration missions

o f t h e flature. The foregoing series of reports on our progress


t o date indicates t h a t a mall, but significant advancement has
been merde by virtue of negative as w e l l as positive findings.

Frcrar. PKMl, the crrrdiavascular Reflex Experiment, we have learned


that a preventive measure against circulastory de-adaptation

which has proven valid on the ground has not been successful i n
flight. This has l e d t o the scheduling of a new and more prom-

ising therapeutic measure f o r trial aboard ApoUo. The tilt

table studies have confimed the tendency towsrd cardiovascular

deconditioning and show some evidence that a s e l a u c e of a


trend pattern nae;y be emerging. The need for determining specific
causal relationships w i l l require the repetition of these studies
during space flight missions and the d e n s i o n of associated

grouad-based studies. The clear-cut evidence of individual


variatiopl in these as w e l l as &her findings f'urther emphasizes
this need.

282
reduction of red cell 8~88swss clearly demnstrrrted during
the Gemini 4, 5, and 7 missiems. Ground-based studies suggest

that this was am, at least i n part, to *e lca~qboxygen at8los-


phere. M e r hi&* sophisticated ramifications of t h i s
study into the field of red cell enzylmology are currently
being carried out. !l%ey &ow promise of data which prove
t o be of importance to clinical aredicine as well as space mdi-

cine, thanks to the problem definitions brought aut by this


investigation.

The fact that total blood VQ~UBK! waa reduced in shorter duration

flights and unchanged at the erad o f the lbday fli&at lllra~r support
the concept that the Gaaruer and Henry reflex, which reduces plasnra
volume, psed es ear3y and for a relatively short time to be
superseded later by a compensatory rise in plasnra volume. On the

other hand, thits finding maybe a reflection of lessemdthenaal


stress, improved food and fluid intake, and increased exercise
which characterized the 14-dag flight. The fact a t there wa8
evidence of dehydrsGiors conmatPg. with an unaltered blood
v o h w and even an inereaaed pia- volume after the 14-day

flight atey prove to be a very significant contribution to our


kwwledge of the basic physiological arschanisaae of dehydration
CiPCUhting blosd -1- Control*

The Exercise Toleraace Experiment, MOO3, Bas &own urb that a


heavier exercise r e e n will be respired far its successf'ul

accopaplisbment in the hture. By virtue of its relatively law


sensitivity, a provocative exercise reghen of this sort may
load it8elf t o calibration as a specific predictive index of

eiqpificaat cariliavascular change on mure flights.

M004, the Phonalectrocardiographic Experiment, brought forth


PO evidence of change relatable t o the space eDmirollselDt. This

woa3.d seem t o refute the Soviet interpretations of their seisma-

cardiographic data. sfhe validity of these negative findings i s


given sone support by the absence of evidence of lqrocaucdial dis-
t w h n c e by erny other metbod of seB8\uTenent utilized.

Experiment E%oo5, the Bioassay of Body Flmids, b e provided a


beginaine insight into the mechanisms of several ph;ybliological

responses of nan t o space flight. U r i n a r y aldosterone chsmges,


never before =amred, have been identified which clln be linked
t o corresponding changes observed in f l u i d axid electrolyte
balance. The determination of epWphrine, norepinephrina, and
17-hydr~co1=ticosteroid cnitplrt levels ha8 raised questiom8 and
given soam speculative e l w s t o their relative roles in hmau
envirolpprsntral pbysislogy. !?he cantinuation of this effort on
f’uture mlssions will be followed w i t h very close interest by

those who have a responsibility i n f l i g h t crew sumport; i n

space flight.

‘pht Boae Densituitetry BrperiBpbnt, XW6, has demonstrated what


hss laerrg been anticipated; that them is, indeed, a reduction

284
of bone density dur- space fliat. Al.thaa@ these changts
have nub been severe, this experiment has Further stwcm that
bons density redactios in the non-vei@tbea&r;ng bones (upper
extmmkties) was elearly more proaaunced than that seen in
ther 88p6 areas dur3ng esluj=oalsnt periods of bed rest on earth.

ss dfected by
the l4-dryy flie;ht than by either the 4- or 8-iiay flights. The
re88opis for this are not clear, bat here
variation amst be sepa,rated f r o m the
diminished thermaat stress, increased fax3 aa8 water in-,
and inemased exercise prograaa whfch characterized the environ-
oent and events of the 14-day flight.

Data fropa MfWT, the Mineral 13alaslce

moderately elevated calciIlrm


psrted outpat of nitrogen and

silaple and accurate Urfnary 8

the value of this investigative effort to ~ ~ ~ s t iof ~ t i o ~


f l i g h t crew support for protracted flights of the future.

'phe glectroencephologra@ic Analysis of Sleep, MOO8, has accurately


petrayed the sleep petterns which actm3ly- did QCCUT daring
f'ligbt. It also raised a question, as is flvguent3y the case
during the progress of any research; the question of the slgoffi-

cance of the slightly increased theta wave sctivity observed.


Experiment WOg, Honarr Otolith Functian, elicited l i t t l e or
no evidence t o -8% a change i n otolith m c t i o n during
flights of up t o 14 aa~rsi n the Gemini configuratiom. This

would tend either t o contradict Smiet findings or t o verify

our crew selection criteria and training procedures as compared


with those employed by the Soviets. While our total data points

are still too few t o establish the absolute absence of otolith


effect, we can now assume w i t h reasonable confidence that there
probably w i l l be no untoward otolith effect of practical sigpd;pi-
came within 14 dqys. The pursuit of t h i s investigation in

Apollo fli@t crews who, l i k e the Soviet cosmonauts, w i l l not


be restrained within the spacecraft will add further cUriFying
data. Repetition during longer flights of the fiture w i l l be
necessary t o extend the time l i n e since the possibility of the
Wer occurrence of otolith changes cannot be ruled aut. The

investigation of saaicircular canal effects I s planned for the


AAP program.

The four major obJective8 of the Medical Experiments Program,


as has been illustrated by today's progress report, aze being
pursued. In quick review, they are to determine effects,
mechanisms, predictive means, and mst effective preventive or

corrective pressures. All of the G e m i n i experiments are directed


tmard the first objective, the determination of the effects of

space flight on man and the time cou~se8of these effects.

286
hhrperlnmts MOO4 (the Phor&oelectrocardiogram),Epoo5 (Bioassay
ef BxIy Fluids), MOO7 (Mineral ce), 211009 (Huarsn OtoUth
Iphactim), end tbe re8 c e l l ma88 and blood volume studies are
all contribatiag data on mechanism by which these effects
are lnsnifested. MOO3 (In-Fligbt b r c i s e r ) pray prove t o be
of value as an in-flight predictive index of circulatory
changes as they might uafamrably affect post-flight activities.
ina ally, Eqteriment MOOI( C a r d i o v a s u Ratflex) i s the evaJ.ua-

tion of a technique t o prevent circulatory de-adaptation during


space flight. The Medical Experiments Program is desiepsed to
enable us t o effectively plan and wwry aut long duration iu8nned
missions of the Rzture. Our data appear t o have eonfimd,

from a medical viewpoint, the feasibility of the Apollo lunar


landing mtssion, and they support the practl-cality of currently
planning a 28-30-aa~r mission. Although the program is very
young, it ha8 also yielded data which promises to contribute t o

OUT knowledge of basic physiology, particularly in the areas of


red c e l l enzymology, and dehydration md fluid balance.

Finally, it should be note?. that the program’s successes t o


date reflect the ability, diligence, and teamwOrk of the perrtici-
pating outside scientific community, NASA center medical canmamity,

and astronauts. ‘phe individuals are a l l deserving of u n s t i n t m


Credit

GPO 9 1 8 - 0 7 4

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