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Amy L. Throckmorton
Biomedical Engineering Department,
Virginia Artificial Heart Institute,
University of Virginia,
Charlottesville, VA USA
Houston G. Wood*
Mechanical and Aerospace Engineering
Department,
Virginia Artificial Heart Institute,
University of Virginia,
Charlottesville, VA USA
James F. Antaki
Associate Professor
Biomedical Engineering and Computer Science,
Carnegie Mellon University,
Pittsburgh, PA USA
Don B. Olsen
Utah Artificial Heart Institute,
Salt Lake City,
UT USA
Introduction
Left ventricular assist devices LVADs have been used as a
possible bridge-to-transplant treatment for patients with heart disease and congestive heart failure. Several of these devices, such as
the DeBakey axial VAD, Jarvik 2000, Medtronic Biomedicus assist system, and the Berlin Incor I, were designed and
developed during the last few decades with successful animal and
clinical trials 1 4. Almost all of the LVADs currently being
developed are continuous flow rotary blood pumps, and these devices provide supplemental mechanical circulatory support to the
native left ventricle. The prospects of these devices for long-term
support of patients, as an alternative means to transplantation, is
dependent on excellent blood compatibility. Therefore, it is essential to quantify levels of blood trauma for successful design of
rotary blood pumps.
Hemolysis, the breakdown or destruction of red blood cells,
causes the contained protein hemoglobin Hb to be released into
the surrounding medium 5 6. Hemoglobin readily binds oxygen
in the lungs and delivers it to the peripheral tissues to ensure
cellular metabolic function. Continuous destruction of red cells
reduces the bloods ability to transport oxygen, increasing risk of
morbidity to the patient. In addition to preventing hemolysis, the
design of the blood flow path must also minimize possibilities of
flow stagnation.
Flow stagnation or conditions where blood pools in one location for a period of time while in contact with a foreign surface
may activate the bodys coagulation cascade and potentially result
in an immunologic response 6. This cascade activation may produce blood clots or thrombi. Release of a thromboemboli into the
*Corresponding author
Contributed by the Fluids Engineering Division for publication in the JOURNAL
OF FLUIDS ENGINEERING. Manuscript received by the Fluids Engineering Division
April 1, 2003; revised manuscript received November 17, 2003 Associate Editor:
Y. Tsujimoto.
blood stream could lead to the obstruction of capillary beds, possible stroke conditions, and likely death of surrounding oxygen
deprived tissue and muscle.
Prior experimental studies have revealed that both Reynolds
turbulent and viscous shear stresses throughout the pump contribute to blood damage 713. Reynolds stresses occur as a result of
momentum transfer due to the turbulent flow conditions. Viscous
shear stresses, however, arise because of the intermolecular frictional forces within the fluid itself. In this study, these stresses are
considered to describe the level of trauma experienced by the
blood as it travels through the LVAD.
Numerous studies have reported on fluid induced hemolysis
923. According to these studies, techniques for predicting or
measuring the levels of hemolysis fall into three categories: computational fluid dynamics CFD 1921, flow visualization
15,17,18, and in vitro blood tests 5,9,16,18. CFD analysis, a
straightforward and cost-effective approach, enables the prediction of shear stresses through the fluid flow field and has been
widely used as a design tool for artificial heart pumps 24 30.
Flow visualization using particle image velocimetry PIV provides measurements of the fluid velocity field that can validate
CFD results; however, neither CFD nor flow visualization can
intrinsically provide measures of blood damage. To directly measure red cell destruction requires in vitro experiments in which
whole blood is circulated, sampled, and analyzed for released
hemoglobin.
Earlier experimental investigations utilized rotating viscometers, cone-and-plate viscometers, flow jets, pulsating gas bubble
tests, and oscillating wire experiments to analyze the effects of
shear stresses on blood samples, including human and animal
blood 5,9. The plasma free hemoglobin level was measured using the cyanmetheglobin method, and the ratio of free hemoglobin
content to total plasma hemoglobin was calculated, which corresponds to the extent of hemolysis. These experiments demon-
(1)
Fig. 1 Centrifugal Blood Pump Prototype-CF4b: This VAD includes an inlet elbow, spindle, impeller, clearance region between the rotor and housing, exit volute and diffuser.
(2)
Here, Hb is the hemoglobin content, dHb represents the damaged hemoglobin content, signifies the characteristic scalar
stress, T is the stress exposure time, and C, , correspond to
constants that can be obtained by regressing experimental data.
Therefore, researchers obtain different values for the constants
depending on experimental conditions. The values C3.62
105 , 2.416, and 0.785 have been used by Mitamura
et al. 19 for their study of rotary blood pumps; but, in that study,
only took into account the turbulent Reynolds stresses. They
assumed that these stresses dominated the viscous stresses occurring in the pump. This group measured hemolysis levels in vitro
and calculated dHb/Hb ratios, which demonstrated a reasonable
correlation.
In another study 9, a different set of constants was found to be
C1.810 6 , 1.991, and 0.765. These constants were
obtained by regression of experimental data taken with an exposure time of 0.0034 to 0.6 s for shear stresses between 40 and 700
Pa in a Couette viscometer. This range of investigation is comparable to the flow conditions in blood pumps.
Apel et al. 23 applied a Lagrangian approach to assess the
stress distribution and related exposure time in a microaxial blood
pump. The viscous stresses were found to dominate the flow field
compared to the Reynolds stresses. They determined the coordinates of each streakline using Euler forward integration of the
particle velocity, as shown:
x i,t x i,t1
with
dx i,t1
t
dt
(3)
dx i,t1
i, p
dt
(4)
This relationship includes turbulent and viscous stresses. As erythrocytes travel through the pump, they experience time-varying
shear stresses. An integrative approach is used to cumulatively
estimate the damage to red cells:
outlet
inlet
inlet
Applying the Reynolds-Averaging process for incompressible fluids, Eq. 12 shows the conservation equation describing the mean
momentum:
Ui
U i U j
u i u j
t
x j
xi x j ij
(7)
u i u j t
Ui U j
2
i jk
x j
xi
3
i j v
(5)
(6)
(8)
outlet
Ui
0
xi
Ui U j
x j
xi
(9)
t c
k2
(10)
CF3 pump resulted in the acquisition of fluid velocity components, which correlated within 1015% of CFD results using the
k- model turbulence model 34,35. PIV measurements for the
impeller and clearance regions of the Cf4b prototype are currently
underway, but are not available for direct comparison to CFD
results at this time. Once the flow measurement results are available, this choice of turbulence model will be rigorously evaluated.
In addition to calculating averaged velocity flow fields and
pressure gradients, TASCflow includes the ability to determine the
shear stress at any nodal location in the flow field. Qualifying and
quantifying the shear stress within the pump allows designers to
estimate whether hemolysis or thrombosis may occur and adjust
design parameters accordingly to reduce the likelihood of occurrence.
To account for the 3-D nature of the shear field, we adopted
scalar stresses as originally introduced by Bludszuweit 12,13:
1
6
ii j j
2
ij
1/2
(11)
Results
Based on convergence of each simulation, the blood damage
index D was computed according to Eq. 5. Figure 2 shows the
isotimic plot of the scalar shear stress along the blade-tip surface.
This surface has historically demonstrated the highest level of
shear in the heart pump maximum value of 250 Pa. Figures 3
and 4 illustrate several representative streaklines, colored according to exposure time and shear stress, respectively.
Most, 322 of 388, blood particles took less than 0.19 seconds to
travel completely through the pump. The mean residence time was
0.34 s with a maximum residence time of 5.3 s due to a possible
vortex region. Figures 5 and 6 demonstrate the particle distributions of exposure time and blood damage index, respectively. The
mean value of the blood damage index was found to be 0.21%
with a maximum value of approximately 2.04%. For 313 of 388
particles, the blood damage index remained less than 0.16%. This
low blood damage index indicates that cells traveling along these
streaklines are not likely to be ruptured. For the remaining 75
particles with damage index values ranging from 0.21% to 2.04%,
there is a greater possibility of damage to the particles, especially
at the higher end.
Fig. 6 Distribution of Exposure Time for Population of Particles Studied: Approximately 322 of the 388 particles in this
study took less than 0.19 s to travel through the computational
flow model. Average residence times are 0.34 second with a
maximum exposure time of 5.3 s due to a possible vortex region.
far more area under the curve ie. higher shear stress, longer exposure time on Fig. 8 than particles #1, #3, and #10 as seen in
Figs. 7, 9, and 11.
Additionally, this blood damage analysis allows designers to
easily calculate the rate of change in the shear stress over time.
Due to the discrete nature of the data points, the slope can be
readily determined and plotted as shown in Figs. 12 and 13 for
particles #2 and #3, respectively. The rate of change in the shear
level over time can also have a large impact on hemolysis
5,9,11. Dramatic increases and abrupt decreases in the shear rate
may lead to red cell rupture or significant damage. Figures 12 and
13 display the exposure of these particles to abrupt changes in the
shear rate d/dt, which contribute to their overall damage indices
and increase the likelihood of particle damage or trauma.
Normalized Index of Hemolysis. The equation developed by
Koller and Hawrylenko 42 is often used to express blood damage as a normalized index of hemolysis NIH as shown here:
NIH g/100L
(12)
dHb
Hb
(13)
mock loop circuit. They tested fresh bovine blood flow of 5 LPM
while maintaining a pressure of 100 mmHg at a physiologic temperature for three hours. Equation 13 was applied to our results
in order to estimate dHb/Hb values for five clinically available
blood pumps.
Numerous in vitro hemolysis studies have been conducted on
existing VADs. Table 2 displays a list of clinically available centrifugal pumps with their corresponding NIH values and estimated
dHb/Hb or damage indices according to Eq. 19. These NIH val-
ues were obtained in vitro using fresh bovine blood in a test loop
under conditions of 6 LPM at 120 mmHg for six hours at room
temperature 21C 45.
The maximum value of our damage index was estimated to be
approximately 2%. This value is of the same order of magnitude
as the indices approximated for the clinically available VADs,
which lends credence to the approach introduced in this paper for
estimating blood damage. Several improvements, however, should
be made to enhance this blood damage model: 1 experimental
NIH values from mock loop testing 2 more realistic constant
Particle
#1
#2
#3
#9
#10
Damage Index
0.087%
1.22%
0.045%
1.26%
0.013%
Centrifugal Pump
NIH value
g/100L
dHb/Hb
0.00070
0.00096
0.00066
0.00090
5%
6%
4%
6%
Figure
7
8
9
10
11
Conclusions
Quantifying levels of blood damage within LVADs is essential
to ensuring a reliable and effective VAD reaches market. This
study describes a cumulative approach to evaluate the stressinduced hemolysis occurring in a miniature centrifugal blood
pump using CFD technology. We analyzed scalar shear stresses
and the exposure time of these particles to such stress levels in the
pump. A Lagrangian particle tracking technique was used to obtain the stress history of 388 representative particles along their
streaklines. An integrative computation makes it possible to consider the damage history of each particle.
The results suggest this blood pump prototype has an acceptable level of hemolysis for steady-state flow simulations. The
maximum damage index found in this study is the same order of
magnitude as those estimated in clinically available VADs. Future
experiments that measure the flow conditions through the pump
and estimate levels of shear stress may enable the validation of
these damage index estimations. Benchtop blood bag testing will
also provide insight into hemolysis levels in the VAD. Additionally, exploring the results for a transient translational sliding interface computational case, which allows the impeller real-time
rotation, would also enable more sophisticated computational
analyses of potential damage index values. Transient CFD simulations would reflect a more realistic implant scenario because
they account for variation in the relative position between the
blades and housing.
In general, CFD was shown to be an effective and useful tool
for the general assessment of stress induced hemolysis in a LVAD
based on the results of this study.
Acknowledgments
The authors wish to acknowledge the financial support for this
work provided by the Utah Artificial Heart Institute, Department
of Health and Human Services, National Institutes of Health, the
National Heart, Lung, and Blood Institute: Grant number: R01
HL64378-01, and the National Science Foundation ITR/ACS
ACI-0086093.
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