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C 2006)

Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006), pp. 517526 (
DOI: 10.1007/s10620-006-3164-5

Relationships Between Intragastric Food


Maldistribution, Disturbances of Antral
Contractility, and Symptoms
in Functional Dyspepsia
LUIZ E. A. TRONCON, MD, PhD,* JOSE RUVER HERCULANO JR, MD, PhD,*
ROBERTA D. SAVOLDELLI, MD,* EDER R. MORAES, PhD, MARIE SECAF,*
and RICARDO B. OLIVEIRA, MD, PhD*

We investigated the relationships between intragastric food maldistribution and antral dysmotility in
functional dyspepsia, and whether these abnormalities relate to meal-induced symptoms. Intragastric
distribution of food throughout gastric emptying was determined in patients (n = 24) and controls
(n = 38) after a liquid nutrient meal labeled with 99m technetium phytate. Antral contractility was
also periodically assessed by dynamic scintigraphy and postprandial symptoms were monitored
with visual analog scales. Residence of food in the proximal stomach was decreased in 8 (33%) and
antral contractility was increased in 9 (37.5%) and decreased in 2 (8%) patients. Proximal and distal
stomach motor abnormalities were neither significantly correlated nor associated. Increased antral
contractility was significantly correlated (Rs = 0.54; P < .01) with postprandial nausea. We conclude
that diminished residence of food in the proximal stomach and disturbed antral contractility occur
independently in different subsets of functional dyspepsia patients. Increased antral contractility
seems to play a role in postprandial nausea in functional dyspepsia.
KEY WORDS: antral contractility; functional dyspepsia; gastric accommodation; gastric emptying; gastric motility;
symptoms.

Functional dyspepsia is a common clinical syndrome characterized by chronic upper abdominal symptoms, such as
epigastric pain or discomfort, fullness, early satiety, and
nausea, without any underlying organic abnormality identifiable by conventional diagnostic tests, including upper
gastrointestinal (GI) endoscopy (1). Functional dyspepsia
is a heterogeneous condition, which is indicated by the fact
Manuscript received December 15, 2004; accepted July 1, 2005.
From the *Division of Gastroenterology, Department of Medicine,
Ribeirao Preto Faculty of Medicine and Department of Physics and
Mathematics, Ribeirao Preto School of Sciences (FFCLRP-USP), University of Sao Paulo, Campus of Ribeirao Preto, Sao Paulo, Brazil.
Address for reprint requests: Professor Luiz E. A. Troncon, Depto.
Clnica Medica, Hospital das Clnicas, Campus da USP, CEP: 14048900, Ribeirao Preto, State of Sao Paulo, Brazil; ledatron@fmrp.usp.br

that patients present with different predominant symptoms


(1), as well as by the variety of different pathophysiologic
mechanisms that have been demonstrated in this disorder
(2).
It has been increasingly accepted that symptoms in
functional dyspepsia patients may result from alterations
in GI motility and visceral hypersensitivity, as well as
from psychosocial abnormalities (1, 2). As far as GI motor disorders are concerned, it has been shown that patients
with functional dyspepsia may have delayed gastric emptying (2), impaired accommodation of ingested food in
the proximal stomach (25), disturbed antral contractility
(68),and altered duodenum and jejunum motility (8).
Gastric motor functions are performed by 2 distinct
morphologic and functional compartments, namely the

Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)


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TRONCON ET AL.

proximal and the distal stomach, which interact under a


number of physiologic control mechanisms (9). In normal
circumstances, the proximal stomach relaxes to accommodate ingested food, which is followed by gradual redistribution of gastric contents to the distal stomach (9).
Peristaltic contractions sweeping the gastric antrum provide grinding of solid particles, mixture of contents with
gastric secretions, and eventually the transfer of chyme to
the duodenum (9). It has been consistently demonstrated
that patients with functional dyspepsia may have impaired
accommodation of food in the proximal stomach (25).
This abnormality is likely to be the cause of early and increased transfer of gastric contents to the distal antrum
(10), which in turn may distend excessively the distal
stomach (11).
Mechanical distension of the gastric antrum in animals
can either enhance or inhibit antral contractility, depending on the degree of distension (12, 13). Additionally, distension of the gastric fundus in humans can affect antral
contractility in a similar way (14). These effects are likely
to be mediated through gastrogastric reflexes (9). Thus,
disordered transfer of gastric contents from the proximal
to the distal portion of the stomach or increased fundal
pressure might theoretically explain disturbed antral contractility in functional dyspepsia patients. Previous work
in patients with functional dyspepsia using manometry (6)
or ultrasonography (15, 16) has demonstrated decreased
antral contractility, but other studies employing dynamic
antral scintigraphy (7) or sonography (17) have shown increased amplitude of antral contractions in this condition.
Nevertheless, the relationships between decreased retention of food in the proximal stomach and disturbed antral
contractility in functional dyspepsia have not been investigated so far.
Although substantial proportions of functional dyspepsia patients show a definite association between symptoms
and meal ingestion (1, 2), the role of disturbances of gastric motor performance in the origin of specific dyspeptic
symptoms is still incompletely understood. Delayed gastric emptying has been shown to be associated to fullness
or vomiting (18, 19), whereas defective gastric accommodation (5) and intragastric meal maldistribution (20)
were found to be associated to early satiety. However, in
most of the studies reporting disordered antral contractility in functional dyspepsia, a correlation between this
type of motor abnormality and specific symptoms was
not looked for (6, 7, 17). Also, the relationships between
gastric motor disturbances and symptoms in functional
dyspepsia have been most frequently determined with a
focus in symptoms recorded with questionnaires applied
at patient inclusion in the studies, but not on sensations
actually elicited by ingestion of a standardized meal.

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Because the relationships between proximal and distal stomach motor abnormalities are still unclear and the
reports on antral contractility in functional dyspepsia patients are somewhat conflicting, we designed this study to
assess whether decreased retention of food in the proximal stomach and disturbed antral contractility might be
related in this common clinical condition. We also aimed
at determining possible associations between intragastric
maldistribution of food or abnormalities of antral contractility to specific symptoms actually elicited by ingestion
of a standard test meal in functional dyspepsia patients.
MATERIAL AND METHODS
Subjects. Twenty-four patients with functional dyspepsia
(9 men and 15 women of median age 33 years; range, 17
57 years, median body mass index [BMI]: 21.6 kg/m2 , range,
19.727.7 kg/m2 ) and 38 healthy asymptomatic volunteers
(20 men and 18 women of median age 29 years; range, 18
49 years; median BMI, 24.6 kg/m2 ; range, 19.630.3 kg/m2 ;
P > .20 versus patients) selected from the local hospital medical and staff population were included in the study, after giving
written informed consent. The investigation was carried out according to the Declaration of Helsinki and the local Ethics Committee previously approved the protocol for the study (Statement 4685/99). All patients presented with upper abdominal
pain and/or discomfort, which were not explained by any organic abnormality found in conventional tests, including upper
GI endoscopy and abdominal ultrasonography. The diagnosis of
functional dyspepsia was then carried out according to Rome II
criteria (1), which included pain or discomfort centered in the
upper abdomen, occurring for at least 12 weeks in the last year, in
the absence of evidence of organic or metabolic disease and not
fulfilling criteria for irritable bowel syndrome. According to the
results of a structured questionnaire administered on inclusion
in the study, all patients had typical dyspeptic symptoms, such
as epigastric pain, postprandial fullness, early satiety, nausea,
and vomiting. In all patients, a definite relationship of symptom appearance or worsening with meal ingestion was found.
In 20 (83.3%) patients, symptoms were regarded to be relevant
enough, so as to interfere with daily activities.
None of the subjects included in the study was a smoker,
had other diseases (including peptic ulcer), or had previous abdominal operations, except for appendectomy. The presence of
diabetes mellitus, renal insufficiency, Chagas disease, and gallstones was ruled out by the appropriate tests. All drugs in use
were discontinued at least 1 week before the test. Women were
studied in the first half of the menstrual cycle, so as to avoid undesirable hormonal influences on the results of gastric motility
tests (21).
Symptom Questionnaire. Upon inclusion in the study, each
selected patient was asked to answer to a structured questionnaire
aimed at detecting and quantifying the intensity of 6 dyspeptic symptoms: heartburn, epigastric pain, postprandial fullness,
early satiety, nausea, and vomiting. Patients were required to
quantify the intensity of each specific symptom using a 4-point
scale as follows: 0, absent; 1, mild; 2, relevant but not interfering
with daily activities; and 3, severe enough to interfere with daily
activities. Patients were also asked to estimate the frequency of
each reported symptom using another scale, as follows: 1, only
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GASTRIC DYSMOTILITY AND DYSPEPSIA


occasionally (less than twice a month); 2, twice or thrice a month;
3, twice or thrice a week; and 4, every day.
Patients were regarded as having relevant presenting symptoms when scoring at least 2 in the intensity scale and 3 in the
frequency assessment, for at least 1 dyspeptic symptom.
Assessment of Gastric Emptying and Intragastric Meal
Distribution. After an overnight fast, subjects ingested 320 mL
of a liquid test meal containing 437 kcal (64 g carbohydrate,
20 g protein, and 11 g fat, 800 mOsm/kg) and prepared as
described elsewhere (22). Before ingestion, the test meal was
labeled with 72 MBq (2 mCi) of 99m technetium coupled with
phytate (Phytosyd, Sydma Medical Equipments and Reagents,
Ribeirao Preto, State of Sao Paulo, Brazil) as a nonabsorbable
carrier. Immediately after meal ingestion, static images corresponding to anterior and posterior aspects of the radioactivity
inside the stomach were simultaneously collected from subjects
standing between the low-energy, high-sensitivity collimators of
a dual-headed gamma camera (Sopha Vision DST, Sopha Medical Vision America, Twinsburg, OH, USA). The acquisition apparatus was connected to an image processing system. Further
serial images of the abdomen were then taken every 5 minutes
during the first 20 minutes, and then at 10-minute intervals up to
90 minutes; whenever delayed gastric emptying was suspected
by visual inspection of gastric images, the studies were extended
up to 120 minutes. The camera was set up to record activity with
a 20% window around the 140 keV photo peak of 99m technetium.
Subjects sat while drinking the test meal and in the intervals between image acquisitions. All images were stored for further
analysis.
Data Analysis for Gastric Emptying and Intragastric Meal
Distribution. A region of interest (ROI) corresponding to the
total stomach was outlined with a cursor over the largest anterior gastric image obtained from the first 3 acquisitions (at 0, 5,
or 10 minutes after the meal), in which gastric accommodation
was expected to be maximal. This ROI was then subdivided into
2 regions corresponding respectively to the proximal and distal gastric areas, so as to represent 2 halves of the ROI for the
total stomach (10, 22). The line separating these 2 regions was
set so as to form a right angle with the longitudinal axis of the
stomach (20, 23), at a level where proximal and distal areas contained nearly half of the number of pixels present inside the ROI
for the total stomach (10, 22). The ROIs corresponding to each
region (total, proximal, and distal stomach) were copied and inverted, so as they could fit the posterior images. Counts obtained
throughout the study from all anterior and posterior ROIs were
recorded and stored. These data were then corrected for physical isotope decay, and the geometric mean of the anterior and
posterior counts was computed to correct for the effect of the
posterior-to-anterior movement of the marker within the body.
For each region (total, proximal, and distal stomach) activityversus-time curves, expressed as percentages of activity in the
total stomach immediately after the end of meal ingestion, were
obtained. Analysis of the curve for the total stomach allowed
calculation of gastric emptying half-time (t1/2 ), expressed as the
time (in minutes) taken for the initial activity in the total stomach
to fall by 50%. In those subjects with total gastric retention at 120
minutes higher then 50%, this parameter was obtained by graphic
extrapolation. For the assessment of intragastric meal distribution, counts obtained from the anterior and posterior proximal
regions of the stomach were also geometrically averaged, corrected for isotope decay, and further corrected to correspond
exactly to 50% of the total stomach, on the basis of the observed
Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)

number of pixels enclosed in each segmental ROI (22). Assessment of intragastric distribution was done by calculating overall
residence of food in the proximal stomach throughout gastric
emptying, which corresponded to the ratio between the areas
under the curves (AUC) representing the proximal (AUCprox )
and the total (AUCtot ) stomach.
Antral Contractility. In all functional dyspepsia patients
and in 14 control subjects, antral contractility was assessed by
dynamic antral scintigraphy using the technique described by
Urbain et al. (7). Immediately following the acquisition of the
static images corresponding to the time points 15, 30, 60, and 90
minutes after test meal ingestion, a dynamic set of 240 frames
(1 frame/sec) from the anterior aspect of the abdomen was acquired for 4 minutes (1 frame/sec). Subjects stood still in the
upright position and were specifically instructed not to talk or
move during image acquisition. Each set of images was stored
for further analysis.
Data Analysis for Antral Contractility. The 240 1-second
images of each set of dynamic images were summed up, so as
to form a single 4-minute composite image, which yield a clear
visual resolution of the stomach shape. Over this image, a rectangular ROI measuring 1 812 pixels was then delineated in
the most horizontal part of the gastric antrum, at a mid-distance
between the pylorus and the incisura angularis (7, 21). The activity in this ROI in each of the 240 frames was counted and the
values were plotted in an activity-versus-time curve. Data for
this curve were exported to a personal computer and processed
(24) using programs written in the Mathlab 5.2 environment and
toolboxes (The MathWorks Inc., Natick, MA, USA). Data were
first submitted to digital filtering using a second-order Butterworth filter, with a low-pass cutoff adjusted for 12 oscillations
per minute. Spectral analysis was then performed using the Fast
Fourier Transform, which allowed assessment of antral contractility in the frequency domain. This was expressed as dominant
frequency (DF), defined as the frequency at which the highest Fourier power spectrum was observed. Amplitude of antral
contractions was determined as a regional ejection fraction according to the technique described by Knight et al. (21). Filtered
data corresponding to each set of 240 frames were normalized
so as to correspond to percent variation around the mean of all
counts. An automated analysis routine calculated the average
of the values for the difference between the maximum and the
minimum of each contraction cycle, expressed in percentage of
the maximum (21). For each subject and time interval, an antral
motility index was calculated by multiplying the values for the
DF and those for the average amplitude of contractions (7, 21).
Because preliminary inspection of curves corresponding to the
first (15 minutes) and last (90 minutes) acquisitions showed a
pattern of hardly discernible contractions cycles and further processing indicated highly variable values for either frequency and
amplitude in both control and patients groups, antral contractility
analysis was restricted to the intermediate time intervals (30 and
60 minutes). The individual values for the antral motility index
were then expressed as the arithmetic mean of data obtained at
these 2 time intervals.
Assessment of Meal-Induced Symptoms. All functional
dyspepsia patients and 12 control subjects were evaluated regarding symptoms occurring after test meal ingestion. Preliminary
studies indicated that 3 main symptoms could be elicited by
ingestion of our test meal: epigastric pain, fullness, and nausea. Immediately after meal, and thereafter at 5, 15, 30, 60, and
90 minutes, subjects were required to score eventual symptoms

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TRONCON ET AL.
on 10-cm visual analog scales (VAS) specific for each sensation.
To help subjects to score their symptoms, each scale was complemented with written descriptors set at the following standard
points: 0, I dont feel anything; 3, I feel a little, but it doesnt
bother me; 5, I feel a bothersome sensation of . . . ; and 10,
I feel an unbearable sensation of . . . .
Data Analysis for Symptom Assessment. Patients and controls were regarded as having had any meal-induced symptom
(pain, fullness, nausea) when scoring at least 5 for that particular
sensation, at any moment after test meal ingestion. The sum of
all scores, as well as the highest score attributed for each of the
3 symptoms investigated, were also recorded for each subject.
Statistical Analysis. Data were presented as median and
range, because a normal distribution of individual values for the
variables studied could not be ascertained. Individual values for
gastric emptying t1/2 , overall intragastric distribution (AUCprox
to AUCtot ratio) and antral motility index were regarded as abnormal when falling outside the range obtained in the control group.
Differences between groups and subgroups were analyzed by the
Mann-Whitney U test. Association analysis was performed using
Fishers exact probability test. The Spearman rank correlation
coefficient (Rs) was employed for the assessment of the relationships between the several variables. Differences were taken
as statistically significant for values of P of less than .05.

RESULTS
Gastric Emptying
In the functional dyspepsia group, t1/2 values
(84 minutes; range, 67147 minutes) were significantly
greater (P = .006) than those obtained in the control
group (67 minutes; range, 30105 minutes). Six (25%)
out of the 24 functional dyspepsia patients studied were
found to have delayed gastric emptying.
Intragastric Meal Distribution
The distribution of individual values for residence of
food in the proximal stomach in patients and controls
is shown in Figure 1. In the functional dyspepsia group,
values for the AUCprox to AUCtot ratio (47%; range, 17

Fig 1. Distribution of individual values for the residence of the meal


marker in the proximal stomach (AUCprox to AUCtot ) in control subjects
and patients with FD. Horizontal bars represent median values. The
dashed line represents the lower limit of normality.

520

TABLE 1. RESULTS FOR THE VARIABLES EXPRESSING ANTRAL


CONTRACTILITY IN PATIENTS WITH FD AND IN CONTROL SUBJECTS
Variable
DF (cpm)
Amplitude (%)
Antral motility
index (% var.min)

Control group
(n = 14)

FD patients
(n = 24)

3.00 (2.003.75) 3.00 (2.123.37)


22 (1232)
20 (1137)
49 (3673)
57 (31127)

P-Value
.78
.42
.08

Note. Data are expressed as medians and (range).

63%) were significantly lower (P = .04) than in the control group (56%; range, 4569%). Among dyspepsia patients, 8 (33.3%) were found to have abnormally diminished retention of the food in the proximal stomach.
Antral Contractility
Data for the antral motility variables in both functional
dyspepsia and control groups are shown in Table 1.
The distribution of individual values for the antral motility index in functional dyspepsia patients and controls is
shown in Figure 2. There were no significant differences
between patients and controls regarding either the mean
DF of antral contractions or the amplitude of antral contractions. The values for the antral motility index tended
to be increased in the dyspepsia group, but this difference did not quite reach statistical significance (P = .08).
However, 9 (37.5%) patients in the functional dyspepsia
group had antral hypercontractility, whereas only 2 (8.3%)
patients had antral hypomotility (see Figure 2).
Relationships Between Intragastric Meal
Distribution and Antral Contractility
Values for the antral motility index in the subgroup of
dyspepsia patients with diminished values for the AUCprox

Fig 2. Distribution of individual values for the antral motility index


(average of values for frequency times amplitude of antral contractions
observed at 30 and 60 minutes after meal ingestion) in control subjects
and patients with FD. Horizontal bars represent median values. The
dashed lines represent the upper and the lower limits of normality.
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GASTRIC DYSMOTILITY AND DYSPEPSIA

Fig 3. Distribution of individual values for the antral motility index


(average of values for frequency times amplitude of antral contractions
observed at 30 and 60 minutes after meal ingestion) in the subgroups of
functional dyspepsia patients with normal or decreased values of food
retention in the proximal stomach. Horizontal bars represent median
values. The dashed lines represent the upper and the lower limits of
normality.

to AUCtot ratio ranged 3179 %var.min (median: 44% var.


min) and tended to be lower than those observed in the remaining patients (59%; range 36127%; Figure 3). However, this difference did not reach statistical significance
(P = .09).
There was no significant correlation between the average residence of food in the proximal stomach and the
antral motility index (Rs = .30, P = .14). Also, there
was no significant association between proximal and distal
stomach motor abnormalities (P = .39). Indeed, among
the 8 functional dyspepsia patients with decreased residence of gastric contents in the proximal stomach, there
were the 2 cases with decreased antral contractility and
only 2 of the patients with increased values for the antral
motility index (see Figure 3).
Relationships Between Intragastric Meal
Distribution and Gastric Emptying
In the subgroup of functional dyspepsia patients
with decreased retention of gastric contents in the
proximal stomach, gastric emptying t1/2 values ranged
72147 minutes (median: 102 minutes) and were significantly greater (P = .01) than in the remaining patients
(81 minutes; range, 60108 minutes). However, there
were no significant association (P = .12) between decreased retention in the proximal stomach and delayed
gastric emptying. Also, there was no significant correlation between the average retention of food in the proximal stomach and gastric emptying t1/2 (Rs = 0.29,
P = .17).
Digestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)

Fig 4. Correlation between the antral motility index (average of values


for frequency times amplitude of antral contractions observed at 30 and
60 minutes after meal ingestion) and the gastric emptying half-time (t1/2 )
in controls (top) and FD patients (bottom).

Relationships Between Antral Contractility


and Gastric Emptying
Among dyspepsia patients with increased antral contractility, t1/2 values ranged 67147 minutes (median:
89 minutes) and were similar (P = .19) to those observed in the subgroup of patients with normal or decreased values for the antral motility index (79 minutes;
60105 minutes). Delayed gastric emptying was found in
only 1 out of the 9 patients with antral hypermotility, and
in 1 of the 2 functional dyspepsia patients with decreased
values for the antral motility index. There was no significant association (P = .90) between deranged antral contractility and delayed gastric emptying. However, there
was a highly significant (P = .003) negative correlation
(Rs = 0.58) between antral motility and gastric emptying t1/2 values (Figure 4) in the functional dyspepsia
group, whereas no significant correlation (P > .50) between these 2 variables was found in the control group
(Rs = 0.08).
Characteristics of Presenting Symptoms
Analysis of questionnaires showed that 6 patients had
heartburn, 18 patients reported epigastric pain, 22 had fullness, 18 had early satiety, and 20 reported nausea, among

521

TRONCON ET AL.

whom only 4 reported vomiting. However, when looking


at symptom relevance, it was found that only 4 specific
symptoms met the predefined criteria based on intensity
and frequency of symptom presentation: epigastric pain,
postprandial fullness, early satiety, and nausea. Relevant
epigastric pain and postprandial fullness were present in
18 (75.0%) patients, whereas relevant early satiety and
nausea was found in 16 (66.6%) patients.
Meal-Induced Symptoms
All patients presented with at least 1 symptom after
meal ingestion, although 1 did not fulfill the predefined
criteria for relevance. Analysis of VAS showed that 12
(50%) patients presented postprandial pain, 14 (58.3%)
had fullness and 11 (46%) had nausea. Peak and cumulative scores for pain were 5 cm; 09 cm and 14 cm; 040
cm, respectively. Peak and cumulative scores for nausea
were 2.5 cm; 09 cm and 13 cm; 050 cm, respectively.
None of the control subjects had pain or nausea. Nevertheless, 6 (50%) healthy volunteers presented fullness after
test meal ingestion and there were no significant differences (P > .20) between patients and controls regarding
either peak (5 cm; 19 cm versus 5 cm; 26 cm) or cumulative (28.5 cm; 643 cm versus 27 cm; 936 cm) scores
for fullness.
In all patients, postprandial pain and nausea started
within 15 minutes from meal ingestion. In all of the patients and controls reporting fullness, this symptom started
within 5 minutes from meal ingestion.
Relationships Between Symptoms Characterized With
the Questionnaire and Gastric Motor Parameters
There were no significant differences between the subgroups of patients with or without relevant specific symptoms regarding any gastric motor variable. There was also
no association between the presence of relevant symptom
and the finding of delayed gastric emptying, decreased retention of food in the proximal stomach or deranged antral
contractility. Increased antral contractility tended to be associated with the occurrence of relevant epigastric pain,
but statistical significance was not reached (P = .052).
Relationships Between Meal-Induced Symptoms
and Gastric Motor Parameters
There were no significant differences concerning gastric
emptying t1/2 , between the subgroups of functional dyspepsia patients with or without pain (83 minutes; range,
60118 minutes versus 87 minutes; 67147 minutes), fullness (75 minutes; 69103 minutes versus 74 minutes; 68
114 minutes) or nausea (85 minutes; 60147 minutes versus 80 minutes; 74118 minutes) after test meal inges-

522

Fig 5. Correlation between values for the antral motility index (AMI)
(average of values for frequency times amplitude of antral contractions
observed at 30 and 60 minutes after meal ingestion) and the cumulative
scores in a VAS for meal-induced nausea in functional dyspepsia patients.

tion. Also, there were no significant differences concerning postprandial residence of food in the proximal stomach, between the subgroups of dyspepsia patients with
or without pain (47%; 1762% versus 52%; 3260%),
fullness (50%; 1762% versus 54%; 3762%) or nausea
(51%; 1755% versus 51%; 3262%). On the other hand,
values for the antral motility index were significantly increased (P < .05) in the subgroup with postprandial pain
(77 %var.min; 31127%var.min versus 52 %var.min; 32
60 %var.min), as well in those functional dyspepsia patients with nausea (77 %var.min; 39109 %var.min versus
51 %var.min; 3160 %var.min).
There were no significant associations between delayed
gastric emptying or diminished residence of food in the
proximal stomach and the presence of any specific symptom. Also, there were no significant correlations between
values for gastric emptying t1/2 or residence of food in the
proximal stomach and either cumulative or peak scores
for postprandial pain, fullness, and nausea. On the other
hand, increased antral contractility was found to be significantly associated with nausea (P < .05), but not with
pain or fullness. Also, a significant positive correlation
was found between values for the antral motility index
and the cumulative VAS scores for nausea (Figure 5).

DISCUSSION
Our study shows that substantial proportions of patients
with functional dyspepsia may have decreased residence
of food in the proximal stomach throughout gastric emptying or abnormal antral contractility, and that these regional
disturbances of gastric motility do not seem to be interrelated. Also, delayed gastric emptying, which was found
in one quarter of our dyspepsia patients, as reported by
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GASTRIC DYSMOTILITY AND DYSPEPSIA

others (1, 2, 7, 10, 11, 15, 17), do not seem to be related


with either decreased proximal stomach retention of food
or abnormal antral contractility. These findings add to the
concept of a heterogeneous nature of functional dyspepsia
(1, 2), a common clinical condition in which multiple abnormalities may be present in different subsets of patients.
The present findings of abnormal intragastric distribution of food in a sample of functional dyspepsia patients
presenting with a variety of symptoms and different degrees of severity are similar to those previously reported in
a more selected group of patients with severe dysmotilitylike functional dyspepsia seen in a tertiary referral center
(10), which suggests that this abnormality may be not
restricted to patients with refractory postprandial bloating or early satiety. Decreased retention of ingested food
in the proximal stomach has been ascribed to decreased
fundal accommodation, increased antral compliance, or
both (3, 4, 10, 11). Impaired proximal stomach accommodation to food has been consistently demonstrated in
functional dyspepsia patients using different methods (3
5, 10, 11). On the other hand, antral tone and compliance
have only recently been studied in humans (25, 26) and an
initial observation in patients with functional dyspepsia
suggests that antral responses to either distension or duodenal infusion of nutrients were not significantly different
from those obtained in healthy volunteers (26). Also, our
data do not indicate an association between diminished
proximal gastric retention of food and antral hypocontractility, which would presumably cause decreased resistance to food transfer from the proximal to the distal
stomach.
Unlike others who defined the ROI for the proximal
stomach visually (27), we used a less observer-dependent
technique, by dividing the gastric areas into two halves
(10, 22). This technique was further improved so as to
minimize the effect of retained radioactivity on the size of
proximal and distal gastric areas, by using as a landmark
the longitudinal axis of the stomach (20, 23). In our hands,
this method has given consistent and reproducible results
regardless of variations in stomach shape (unpublished
data).
Although we did not perform simultaneous manometry
or sonography recordings to validate our antral contractility measurements, the actual values obtained for both
frequency and amplitude of antral contractions were similar to those previously reported in healthy volunteers (7,
21) and in functional dyspepsia patients (7) using the same
technique. Lack of data on antral contractility corresponding to earlier (15 minutes) and later (90 minutes) gastric
emptying phases is unlikely to have flawed our results;
studies using either sonography (17) or scintigraphy (7,
21) have shown that shortly (<30 minutes) after meal inDigestive Diseases and Sciences, Vol. 51, No. 3 (March 2006)

gestion both frequency and antral excursion ratio reach


a steady state, which lasts for at least 2 hours. Therefore,
data averaged from measurements taken at 30 and 60 minutes postmeal are likely to represent overall antral motor
performance elicited by our test meal.
Although the differences regarding the antral motility
index between patient and control groups did not reach statistical significance, the finding that 9 out of our 24 functional dyspepsia patients had increased antral contractility
is in line with those by Urbain et al. (7), who found that
both DF and amplitude of postprandial antral contractions
were significantly higher than in healthy volunteers, in a
group of 25 functional dyspepsia patients studied with a
scintigraphic technique. These observations disagree with
a number of studies reporting diminished antral contractility in functional dyspepsia (8, 15, 16). It is conceivable
that such discrepancies may be related to differences in
patient selection or methods. Most of the studies reporting decreased antral motor activity in functional dyspepsia
were carried out using manometry, which is an invasive
technique known to miss a substantial proportion of antral
peristaltic waves, particularly those that did not occlude
the gastric lumen (28). On the other hand, studies on antral
contractility using scintigraphy have shown that this noninvasive method can provide reliable results concerning
changes in motility induced by drugs (29, 30)or associated with disease (7, 31).
Increased antral contractility in functional dyspepsia
cannot be explained by antral distension consequent to diminished retention of food in the proximal stomach; these
2 events seemed to occur in different subsets of patients
(Figure 3). For this same reason, it is unlikely that increased antral contractility results from reflex stimulation
induced by increased intraluminal pressure in the proximal stomach secondary to impaired accommodation to
the ingested meal. Thus, data from the present work cannot support our initial hypothesis that motor abnormalities
regarding the proximal stomach and the antrum in FD patients might be related.
Increased antral contractility might be a consequence
of diminished vagal inhibitory influences on the stomach, which has been found in functional dyspepsia patients (32). Nevertheless, decreased vagal tone or other
evidence of autonomic dysfunction has been associated
with decreased antral motor activity rather than hypercontractility (32, 33), thus suggesting that excitatory pathways are more likely to be affected in functional dyspepsia
patients.
Lack of significant correlation between antral motility
index and gastric emptying rates in controls was in concordance with what was previously shown for the liquid
component of a mixed meal (34) and highlights the fact

523

TRONCON ET AL.

that stomach evacuation is a complex process, which depends on a number of different factors, such as fundal pressure, propagated and nonpropagated antral contractions,
isolated pyloric pressure waves, and duodenal resistance
(9). On the other hand, the present finding of a significant,
negative correlation between antral motility index values
and gastric emptying time in our patients might indicate
a more preponderant role of antral contractions in gastric emptying control in functional dyspepsia. One might
then speculate that increased contractility in dyspepsia patients might occur as a compensatory mechanism against
putative pyloric or postpyloric abnormalities, such as increased intestinal tone and contractility (8), which were
not addressed in our study and might otherwise induce
delayed gastric emptying.
In contrast to other findings (5, 18, 19), we were not
able to show any relationship between specific presenting
symptoms recorded with a questionnaire at inclusion in
the study and gastric motor disturbances. However, the
hypothesis of association cannot be rejected by our data,
because there was a considerable overlapping between different dyspeptic symptoms and we studied a relatively
small number of patients, which precluded multivariate
analysis from being carried out.
As far as the relationships between gastric motor
disturbances and meal-induced symptoms are concerned,
the most striking finding in our study was a definite
association between increased antral contractility and the
occurrence of nausea in functional dyspepsia patients,
with a significant, positive correlation between the
intensity of this symptom and the magnitude of the
antral contractility index. This is rather puzzling, because
earlier studies have consistently shown that this particular
symptom is more commonly associated with antral
hypocontractility and delayed gastric emptying (1, 2).
On the other hand, nausea may be provoked by a variety
of stimuli (35), which may favor the speculation that
either antral distention associated with hypocontractility
and delayed gastric emptying or abnormally increased
excursion of antral walls could elicit nausea in different
subsets of functional dyspepsia patients.
Because postprandial symptoms in our patients occurred soon after meal ingestion, it could be argued that increased antral contractility might have caused early transfer of meal up to the duodenum, which could lead to excessive stimulation of mucosal receptors sensitive to meal
composition (9) and be able to induce nausea in hypersensitive patients, as shown by different authors (36, 37).
Indeed, it was reported in a recent paper (38) that a substantial proportion of functional dyspepsia patients may
have rapid initial gastric emptying, which was associated
with a higher symptom score, and was also a determi-

524

nant of maximum tolerated meal volume. Nevertheless,


we found no patient with rapid emptying nor were we
able to measure antral contractility during the initial phase
of gastric emptying; as mentioned, antral activity-versustime curves showed a pattern of hardly discernible contractions cycles. Moreover, initial rapid emptying would
likely to be associated with subsequent increased fundal
relaxation (36) and greater inhibition of gastric emptying, which was also not apparent in our patients reporting
nausea.
Increased antral contractility might be a consequence
of stimulatory vagal influences on distal stomach contractions elicited by the occurrence of nausea and mediated
through central nervous system (CNS) stimulation. However, nausea elicited by CNS stimulation has been found
to be associated with a decrease in antral contractile activity, which does not seem to be correlated with the severity
of nausea sensation (39).
It is interesting to note that half of our healthy controls
also presented fullness after test meal ingestion. This is in
line with the findings of Hjelland et al. (40), who reported
that healthy volunteers carefully selected were not devoid
of symptoms after ingestion of a caloric nutrient meal, in
a standardized test of gastric motility. This finding indicates that our test meal, with its relatively high calorie and
osmolar contents, actually challenged the mechanisms involved in the origin of dyspeptic symptoms, as much as the
mixed, solidliquid test meal utilized elsewhere (7, 8, 15,
20), while not precluding comparisons between patients
and controls, as well as between different subgroups of
patients. It could also be argued that a solid meal would
be more suitable to study antral contractility, because gastric antral contractions are thought to be more important to
solid, rather than liquid, emptying (9). Nevertheless, there
is evidence that antral contractions are also important for
gastric emptying of liquids (41, 42). On the other hand, we
must admit that our findings are limited to this particular
test meal and could not be generalized to ordinary, mixed
solidliquid meals.
In conclusion, this study shows that decreased residence of food in the proximal stomach throughout gastric emptying and increased antral contractility may occur
independently in different subsets of functional dyspepsia patients, and that this does not support the hypothesis
that disturbed antral contractility in functional dyspepsia might be secondary to intragastric maldistribution of
food. Although we were not able to show any relationship
between delayed gastric emptying or intragastric maldistribution of food and specific postprandial symptoms,
our data support a role of increased antral contractility in
the origin of meal-induced nausea in functional dyspepsia
patients.
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GASTRIC DYSMOTILITY AND DYSPEPSIA

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