247
Increase in Erythrocyte Disaggregation Shear
Stress in Hypertension
Seyed Mahmoud Razavian, Muriel Del Pino, Alain Simon, and Jaime Levenson
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
The aggregation and disaggregation behaviors of red blood cells were investigated in 17 nonnotensive
and 21 hypertensive subjects with a laser reflectometry technique, and simultaneous measurements were
taken of blood viscosity with a coaxial viscometer. Increased red blood cell aggregation (26%, p< 0.001)
and disaggregation shear rate (20%, p<0.01) and shear stress (18%, p<0.01) were observed in
hypertensive subjects when compared with nonnotensive subjects. Similar elevations in hypertensive
subjects were found when the hematocrit was adjusted to 40%. Variation of red blood cell concentration
caused the red blood cell disaggregation shear rate to change in an opposite direction but did not modify
red blood cell aggregability and disaggregation shear stress. The increase of the reversible aggregation of
red blood cells was associated with higher fibrinogen and plasma protein concentrations in hypertension.
An increase in red blood cell aggregability and in the shear resistance of red blood cell aggregates may play
a role in the development of the cardiovascular complication in hypertension. The quantification of red
blood cell disaggregation shear stress, which represents the hydrodynamic force required to disperse the
aggregates, may provide a useful parameter for clinical investigations. (Hypertension 1992^20:247-252)
KEY WORDS • erythrocyte aggregation • stress, shear • blood viscosity • rheology
T
he aggregation and disaggregation of red blood
cells (RBC) play an important role in the
pathophysiological behavior of the blood circulation.1 The aggregation of RBC is a reversible phenomenon that occurs with macromolecules bridging the
membranes of adjacent cells, and it is influenced by 1)
the shearing force of blood, 2) the properties of erythrocytes (concentration, deformability, surface charge,
and shape), and 3) the bridging force of high molecular
weight plasma proteins.2"4 This phenomenon represents
an equilibrium between adhesive forces (macromolecules bridging force), repulsive forces (electrical charges
on RBC surface),5 and mechanical forces (shear
stress).5-6 When the adhesive force is increased in
pathological conditions, the shear stress required to
break up RBC aggregates would become elevated.
In hypertension, increases of red blood cell aggregation were largely extrapolated from blood viscosity
measurements at low shear rates.7-11 In contrast, few
studies have used direct quantitative methods to evaluate red blood cell aggregation in hypertension.12 Relatively little data are available on the shear stress needed
to break up the aggregated RBC in normal and pathoFrom the Centre de M£decine Preventive Cardiovasculaire,
INSERM U 28, Hdpital Broussais, Paris, France.
A preliminary report of this work was presented at the 64th
Scientific Sessions of the American Heart Association, Anaheim,
Calif., November 11-14, 1991, and was published in abstract form
(Razavian SM, Levenson J, Del-Pino M, Simon A: The shear
stress for disaggregating red blood cells is increased in hypertension. Circulation 1991;84:II-53).
Supported by grants from the Institut National de la Santi et de
la Recherche Medicale and the Institut Jean Merlen.
Address for reprints: Dr. Jaime Levenson, Centre de M6decine
Preventive Cardiovasculaire, H6pital Broussais, 96 Rue Didot,
75674 Paris CEDEX 14, France.
Received May 7,1991; accepted in revised form April 13, 1992.
logical conditions. In the present study, we used a new
laser technique that allowed quantification of the aggregation kinetics and of the disaggregation shear rate of
the aggregates.13'14 The simultaneous measurement of
blood viscosity allowed us to determine the disaggregation shear stress as a representative index of the mechanical forces acting on RBC to disaggregate the
rouleaux. Thus, the purposes of the present study are to
determine in nonnotensive and hypertensive subjects
the aggregation kinetics and the disaggregation shear
rate of aggregates and to assess the shear stress needed
to break up the aggregated RBC.
Methods
Twenty-one patients with mild-to-moderate hypertension, who were 44 ±2 years old (mean±SEM) and
had a body mass index (weight/height2) of 24.8±0.6
kg/m2, and 17 nonnotensive control subjects, who were
40±2 years old and had a body mass index of 24.3±0.6
kg/m2, participated in this institutionally approved study
after giving informed consent. Systemic blood pressure
was measured with a sphygmomanometer three times in
each subject with the subjects in a reclining position,
and hypertension was diagnosed when diastolic blood
pressure was between 95 and 114 mm Hg (Korotkoff
Phase V). All the subjects were either not taking any
medication or had discontinued treatment at least 4
weeks before the study. None had cardiac, neurological,
or renal complications or peripheral vascular disease;
essential hypertension was documented by standard
laboratory tests and timed intravenous pyelogram.
A new laser technique (erythroaggregameter, SEFAM, Nancy, France), which had been previously validated,13-15 was used to study the aggregation kinetic and
disaggregation shear rate of blood samples. The blood
was suspended in a narrow gap between two coaxial
248
Hypertension
Vol 20, No 2 August 1992
BSLM
BSL
20
40
60
1
10"
10"
TttlE(t)
FIGURE 1. Left panel: Variation of backscattered light (BSL) as a function of time. Dotted curve corresponds to aggregation
index (AI), calculated during the first 10 seconds after abrupt stoppage of the shearing. BSLM, maximal backscattered light Right
panel: Determination of disaggregation shear rate threshold (yjfrom the ABSLM as a function of shear rate (y). Disaggregation
shear rate threshold was obtained by extrapolating the line of ABSLM versus shear rate plot to ABSLM=0.
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
cylinders; the inner cylinder was fixed; the outer cylinder was transparent and was rotated by a motor. Shear
rates from 7 to 605 sec"1 can be applied to the outer
cylinder. A ray of light provided by a laser diode
irradiated the suspension. The backscattered light
(BSL) by the blood suspension was recorded by a
photoelectric detector as a function of time and of shear
rate. For determination of aggregation kinetics, the
blood sample was sheared for 10 seconds at a high shear
rate so that erythrocytes were disaggregated and oriented with the flow. Then, the shear rate was abruptly
stopped, erythrocytes were no longer oriented, and a
rapid increase in the BSL was recorded. The peak value
characterizes the maximum steady-state value of BSL
(BSLM). Thereafter a progressive decrease in the intensity of the BSL occurred that was related to the
formation of the rouleaux. A mean aggregation index
(AI) (related to aggregation kinetic) was calculated
from the relative area above the light intensity curve
during the first 10 seconds after abruptly stopping the
shear rate (Figure 1). Thirty-two shear rates ranging
from 7 to 605 sec"1 were sequentially applied to the
sample, i.e., from the lowest shear rate (n = l; shear rate,
7 sec"1) to the highest shear rate (n=32; shear rate, 605
sec"1). Between successive shear rates, a lag time of
about 5 seconds allowed the recording of BSLM. The
decrease in shear rate induced a reduction in BSLM
level. The variation of BSLM as a function of shear rate
was then calculated as:
ABSLM=l-[BSLM(-yn)/BSLM (y,2)]
where y is shear rate. When the shear rate increased,
ABSLM decreased and approached zero (Figure 1).
The disaggregation shear rate threshold was obtained
by extrapolating the line of ABSLM versus shear rate
plot to ABSLM=0.
To assess the device reproducibility, coefficients of
variation for replicate tests were evaluated by performing 10 successive runs on the same blood aliquot of a
single donor. We obtained an average coefficient of
variation of 1.5% for AI and 3.3% for disaggregation
shear rate threshold (Table 1). The variability within
subjects was evaluated in 10 normotensive and 10
hypertensive subjects. For each subject five successive
runs on the same blood sample adjusted to 40% hematocrit were performed. We obtained average coefficients
of variation of 1.6±0.3% and 2.1±0.4% for AI and
2.9±0.5% and 4.0±0.4% for disaggregation shear rate
threshold for blood samples from normotensive and
hypertensive subjects, respectively (Table 1). To assess
the long-term variability within subjects, five nonnotenslve subjects were investigated twice. For each subject
two successive runs on the same blood sample adjusted
to 40% hematocrit were performed at 0 and 90 days
after. We obtained an average coefficient of variation of
3.3±1.5% for AI and 2.5±1.1% for disaggregation
shear rate threshold (Table 1).
Blood viscosity was determined in all subjects with a
Couette viscometer with coaxial cylinders (Low Shear
30, Contraves AG, Zurich, Switzerland) that allowed
measurements at several discrete shear rates over a
wide range varying from 0.033 sec"1 to 240 sec"1.11-16
The measurements were taken at shear rates of 240, 96,
52, 11, 2.4, 0.52, and 0.11 sec"1 and were expressed as
milliPascal • second (mPa • sec). Plasma viscosity was
determined at 240 sec"1.
The shear stress needed to break up the aggregated
RBC (disaggregation shear stress) was calculated for
different blood samples from the determinations of
disaggregation shear rate threshold and the blood viscosity at the shear rate equal to disaggregation shear
rate threshold:
where T is disaggregation shear stress, y, is disaggregation shear rate threshold, and 77 is blood viscosity. Blood
samples were obtained from the antecubital vein by
clean venipuncture with disposable plastic syringes be-
TABLE 1. Reproducibility of Red Blood Cell Aggregation and Disaggregation Parameters
Rhcological
parameters
Red blood cell aggregation index
Red blood cell disaggregation
shear rate threshold (sec"1)
Values are mean±SEM.
Intra-assay
variability (n = 10)
1.5%
33%
Intrasubject variability (n=10)
Hypertensive
Normotensive
2.1±0.4%
1.6±0J%
2.9±0.5%
4.0±0.4%
Long-term intrasubject
variability (n=5)
33±U%
2J±1.1%
Razavian et al Hypertension and Erythrocyte Aggregation
249
Biochemical and Rheological Parameters in Normotensive and Hypertensive Subjects
TABLE 2.
PV
(mPa • sec)
1.25±0.02
1.33±0.02
0.001
n
(240 sec"1)
(mPa • sec)
3.82±0.07
4.06±0.06
0.02
AI
Prot (g/l)
Fib (g/l)
(mPa • sec) T (dyn/cm2)
Ht(%)
Subjects
7, (sec"1)
2.03 ±0.04
163±0.6
NT±SEM
2.83±0.11
4.37±0.08
46.7±1.1
43.4±0.6
66.2±0.5
20.1
±0.6
234+0.10
3.49±0.19
4.93±0.08
51.7±1.6
72.7±1.0
45.0±0.5
HTA+SEM
0.001
0.001
0.001
0.02
0.01
0.001
0.05
P<
1
Values are mean±SEM. Ht, hematocrit; Prot, plasma proteins; Fib,fibrinogen;PV, plasma viscosity, 77 (240 sec" ), blood viscosity; AI,
red blood cell aggregation index; -y,, red blood cell disaggregation shear rate threshold; TJ (7,), blood viscosity corresponding to
disaggregation shear rate threshold; T, red blood cell disaggregation shear stress; NT, normotensive subjects; HTA, hypertensive subjects.
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
tween 8 and 9 AM after an overnight fast. Blood was
treated with ethyienediaminetetraacetate, potassium
salt (EDTA) anticoagulant and was used for the determination of AI, disaggregation shear rate threshold,
blood viscosity, plasma viscosity, and microhematocrit.
Plasma fibrinogen level was determined with a fibrometer (BioM6rieux, Charbonnieres-les-Bains, France) by a
thrombin clotting method.17 Plasma protein concentrations were determined with a Gilford spectrophotometer (Ciba-Corning, le Vesinet, France). Microhematocrit was determined in duplicate by use of a Hermle
centrifuge (Roucaire, V61izy Villacoublay, France)
(12,000g for 3 minutes). All rheological tests were
performed at 37°C±0.5°C.
Results
Compared with normotensive controls, hypertensive
patients had higher systolic and diastolic blood pressures
(164±3 versus 117±2 mm Hg,/><0.001, and 101±l versus 74±1 mmHg, /><0.001, respectively). As shown in
Table 2, hypertension was associated with higher values
of fibrinogen (23%,p<0.01), total protein concentration
(10%,p<0.001), and plasma viscosity (6%,p<0.001). In
comparison with normotensive subjects, the hypertensive
patients (Table 2) showed higher values for AI (23%,
/><0.001), disaggregation shear rate threshold (11%,
p<0.O2), blood viscosity at disaggregation shear rate
threshold (13%, /?<0.001) and erythrocyte disaggregation shear stress (26%, /?<0.001) for the whole blood
samples. When the hematocrit of the blood was adjusted
to 40% (Figure 2), the hypertensive subjects again
showed higher values for AI (26%, p<0.001), disaggregation shear rate threshold (2O%,/7<0.01), blood viscosity at disaggregation shear rate threshold (8%,/><0.05),
and disaggregation shear stress (18%,/?<0.001).
20
1S
A
57.3
±1.2 ±2J
18.1 2 U
±O8
±0.9 show red blood cell aggregation index
Bar
graphs
FIGURE 2.
(left panel) and red blood cell disaggregation shear rate
threshold (sec'1) (right panel) in normotensive (open bars)
and hypertensive (filled bars) subjects for blood adjusted to
40% hematocrit. **p<0.01, ***p<0.001.
To determine the influence of hematocrit on RBC
aggregation parameters, the erythrocyte concentrations
of blood samples were varied by adding or removing
calculated volumes of autologous plasma. AI did not
change significantly by varying hematocrit from 30% to
40% to 50%(14.9±1.7,15.8±1.3, and 16.3±0.8, respectively, for normotensive subjects and 19.1±1, 20.3±0.8,
and 18.9±1.1, respectively, for hypertensive subjects).
In contrast, as shown in Figure 3, by increasing hematocrit from 30% to 50%, blood viscosity at disaggregation
shear rate threshold increases while disaggregation
shear rate threshold decreases. Furthermore, a hematocrit-independent disaggregation shear stress was obtained. At any level of hematocrit, blood viscosity at
disaggregation shear rate threshold, disaggregation
shear rate threshold, and disaggregation shear stress
were significantly higher in hypertensive patients compared with normotensive subjects (p<0.05, 0.01, and
0.001, respectively).
Table 3 shows correlations in the overall population
between the aggregation parameters and hematocrit,
plasma proteins and fibrinogen. AI and AI(40%) were
both correlated positively with plasma proteins
(p<0.05) and fibrinogen (p<0.001) but not with hematocrit. Disaggregation shear rate threshold was negatively correlated to hematocrit (p<0.001). Disaggregation shear rate threshold correlated positively with
plasma proteins (p<0.01) and fibrinogen (/?<0.001)
only when hematocrit of blood was adjusted to 40%.
Finally, disaggregation shear stress was positively correlated to plasma proteins (p<0.05) and fibrinogen
(p<0.05). A strong correlation was observed in the
whole population between blood viscosity at disaggregation shear rate threshold and AI (r=0.52, /><0.001)
(Figure 3). Such a correlation with AI was not significant for blood viscosity at 240 sec"1.
Discussion
Two main parameters can be quantified with the laser
erythroaggregameter used in the present study: red
blood cell aggregation related to the kinetics of RBC
aggregates and disaggregation shear rate that provides
the shear threshold required to dissociate the aggregates. The former parameter determines the reversible
tendency of RBC to form aggregates, and the latter
estimates the shear resistance of RBC aggregates.
There are many similarities between this new technique
and the infrared reflectometric method for measuring
RBC aggregation under shear flow.18 As previously
described, the aggregation parameters measured by this
new technique are sensitive to experimental conditions.1413 The reliability of the method was confirmed
250
Hypertension
Vol 20, No 2 August 1992
BLOOO VISCOOTY ft fttH
(raPu)
RED BLOOD CELL WBAOanEOATtON
SHEAR RATE THRESHOLD
RED BLOOD CELL
MtUMOBU
TO •
•0
SO
4J0
40
u>
13
30
HEMATOCflfT%
FIGURE 3. Influence of hematocrit on red blood cell (RBC) aggregation parameters in normotensive (n) and hypertensive (•)
subjects. Note that at any level of hematocrit, blood viscosity at disaggregation shear rate threshold [v(yJ] ('eft panel) and the
shear rate (middle panel) and stress (right panel) thresholds for RBC disaggregation were significantly higher in hypertensive than
in normotensive subjects. *p<0.05, **p<0.01, ***p<0.001.
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
by the low coefficients of variation found in the intraassay and within-subjects (short- and long-term) results
of the present study. Furthermore, the low values of
coefficients of variation were similar between normotensive and hypertensive subjects.
Several Theological abnormalities have been reported
in hypertension; the elevation of whole blood viscosity is
one that is widely recognized.7-11 The hyperviscosity
magnitude observed in hypertensive patients was found
to be inversely related to shear rate.8'11 Because at low
shear rates RBC aggregation is one of the major determinants of increased blood viscosity, low shear blood
viscosity has been used as an indirect evaluation of
rouleaux formation. By focusing directly on RBC aggregation measurements, we differentiated two major abnormalities in hypertension. The enhanced RBC aggregability further confirmed that it led to the increased
blood viscosity in low shear conditions. The strong
association between the blood viscosity measured at
disaggregation shear rate threshold and the AI further
corroborates that red blood cell aggregation is a major
determinant of blood viscosity at low shear rate. Such
an association disappears at higher shear rate as indicated by the nonsignificant relation between AI and
blood viscosity at 240 sec"1. The absence of correlation
between aggregability and high shear blood viscosity is
well established. At high shear rate, the blood viscosity
values, at a given hematocrit, reflect red blood cell
deformability. The second major abnormality observed
with this direct technique was the elevation of disaggregation shear rate threshold, which indicates that the
adhesive force between the RBC in the rouleaux is
stronger in hypertensive than normotensive subjects.
The forces that disaggregate the rouleaux are important
because red blood cell aggregation may occur physio-
logically in vivo.19 However, the simple determination of
disaggregation shear rate does not indicate the forces
needed to break up the aggregates. Disaggregation
shear stress, the product of disaggregation shear rate
and the blood viscosity measured at this shear rate,
represents the hydrodynamic force acting to break up
the aggregates. To our knowledge this is the first time
that abnormalities of disaggTegation shear stress have
been quantified in hypertensive patients.
The hyperviscosity state resulting from increased
erythrocyte aggregation is a function of the level of
plasmatic macromolecules.8 Indeed RBC aggregation
and disaggregation may be influenced by the level of
plasma proteins such as fibrinogen or globulins and by
the hematocrit value. Our study showed that in hypertension, the increase in RBC aggregation is associated
with higher fibrinogen and total protein concentrations.
The role of hematocrit on the kinetics of RBC aggregation as well as on disaggregation parameters was also
investigated in the present study. The disaggregation
shear rate decreased with increasing hematocrit and
therefore with increasing blood viscosity. The disaggregation shear stress, however, was independent of hematocrit in both normotensive and hypertensive subjects.
We observed that the influence of hematocrit on the AI
remained small as previously reported by Chabanel and
Samama.15 Some reports have shown that the aggregation kinetic is dependent on the hematocrit being in the
30-50% range.14-20-21 However, although Donner et al14
reported that a rise in hematocrit is associated with an
increase in the kinetics of aggregation, Schmid-Schdnbein et al20 and Agosti et al21 observed the reverse
effect. In fact, RBC aggregation is a complex process
that involves rouleaux and a network of rouleaux formation, each of which could vary with hematocrit.
TABLE 3. Correlation Coefficient Between Biochemical and Aggregation Parameters
Parameters
AI (unit)
AI (40%) (unit)
y, (40%) (sec"1)
7, (sec"1)
Ht(%)
0.12
0.01
0.10
-038'
0J5t
Prot (g/1)
0.38t
0.43*
0.21
0.62*
Fib(g/1)
0.61'
0.52*
031
T (dyn/cm2)
0.20
0.39t
037t
AI, red blood cell aggregation index; AI (40%), AI at hematocrit adjusted to 40%; y,, red blood cell disaggregation
shear rate threshold; y, (40%), y, at hematocrit adjusted to 40%; T, red blood cell disaggregation shear stress; Ht,
hematocrit; Prot, plasma proteins; Fib, fibrinogen. •jp<0.05, $p<0.01, *p<0.001.
Razavian et al
IB iwdt VlM.cmY AT
(nfM)
Hypertension and Erythrocyte Aggregation
251
•LOOO VBCOSTY AT MO »•
(of
I-
•
10
15
20
29
30
AaOREOATKM INDEX
10
15
20
p.KS
25
30
AOQflSQATlOM MDCX
FIGURE 4. Relation between blood viscosity corresponding to disaggregation shear rate threshold (y,), and blood viscosity at 240
sec'1 as a function of red blood cell aggregation index in normotensive (D) and hypertensive (•) subjects.
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The fact that hypertensive patients had an increased
shear resistance of their RBC aggregates may be a
relevant finding, particularly concerning the risk of
vascular complications that generally are associated
with a low flow status. Indeed, RBC aggregate more
rapidly at stasis, and the shear forces necessary to
disperse the aggregates would be higher than in normal
flow status. Such conditions may exist in ischemic necrosis or infarction, which are well-known complications
in hypertension, and might contribute to the induction
or aggravation of the course of the disease. Furthermore, abnormal aggregations were reported in such
clinical situations as cardiogenic pulmonary edema,22
myocardial ischemia,23-24 thromboembolic states,23 and
retinal venous occlusion.26 The latter is an excellent
model of a lowflowstate at arteriovenous crossing sites.
Arteriosclerotic changes compromise the venous return
at these points to create a lowflowarea that could lead
to venous occlusion; therefore, branch retinal occlusion
is seen in hypertensive or arteriosclerotic individuals.27
It was recently reported that by using the same methodology as in the present work, the abnormal RBC
aggregation and disaggregation shear conditions observed in retinal vein occlusion could predispose to the
onset and development of this complication.26 The
decreased wall shear rate and stress reported recently
by our group28-29 in the large artery of hypertensive
patients may also be relevant to RBC aggregation when
vascular changes occur. In poststenotic regions with
vessel compression and thrombus formation, shear rate
can become very low and favor RBC aggregation,
inducing a further increase in blood viscosity and retardation of blood circulation.
In conclusion, the elevation of RBC aggregation and
the increased shear resistance of their RBC aggregates
can play a major role in the pathophysiology and
development of cardiovascular complications in hypertensive patients.
Acknowledgment
We thank Christine Beuzet for skilled secretarial assistance.
References
1. Chien S: Haemorheology in disease: Pathophysiological significance and therapeutic implications. Clin Hanorheol 1981;1:
419-442
2. Chien S, Usami S, DeUenback RJ, Gregersen MI, Nanninga LB,
Guest MM: Blood viscosity. Influence of erythrocyte aggregation.
Science 1976;157:829-831
3. Schmid-Schonbein H, Wells RE: Rheological properties of human
erythrocytes and their influence upon the "anomalous" viscosity of
blood. Ergeb Physiol 1971;63:146-219
4. Chien S, Lusc SA, Jan KM, Usami S, Miller LH, Fremount H:
Effect of macromolecules on the rheology and ultrastructure of red
cell suspension, in Ditzel J, Lewis DH (eds): 6th European Conference on Microcirculation. Aalborg, S. Karger Basel, 1970, pp 29-34
5. Chien S, Jan KM: Red cell aggregation by macromolecules: Roles
of surface adsorption and electrostatic repulsion. J Supramoi Struct
1973;1385-409
6. Stoltz SF, Donner M: Hemorheology: Importance of erythrocyte
aggregation. Clin Hemorheol 1987;7:15-23
7. Weihmayr T, Ernst E, Matrai A, Paulsen F: Blood rheology in
untreated essential hypertension. Clin Hemorneol 1987;7:457
8. Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh JH: Direct
relationship between blood pressure and blood viscosity in normal
and hypertensive subjects: Role of fibrinogen and concentration.
Am J Med 1981;70:1195-1202
9. Dintenfass L, Bauer GE: Dynamic blood coagulation and viscosity
and degradation of artificial thrombi in patients with hypertension.
Cardiovasc Res 1970;4:50-60
10. Chien S: Blood rheology in hypertension and cardiovascular disease. Cardiovasc Med 1977;2:356-360
11. Levenson J, Simon AC, Cambien FA, Berctti C: Cigarette smoking
and hypertension: Factors independently associated with blood
hyperviscosity and arterial rigidity. Arteriosclerosis 1987;7:572-577
12. Zannad F, Voisin Ph, Brunotte F, Bruntz JF, Stoltz JF, Gilgenkrantz JM: Haemorheological abnormalities in arterial hypertension and their relation to cardiac hypertrophy. / Hypertens 1988;6:
293-297
13. Snabre P, Bitbol M, Mills P: Cell disaggregation behavior in shear
flow. Biophys J 1987^1:795-807
14. Donner M, Siadat M, Stoltz JF: Erythrocyte aggregation:
Approach by light scattering determination. Biorheology 1988;25:
367-375
15. Chabanel A, Samama M: Evaluation of a method to assess red
blood cell aggregation. Biorheology 1989;26:785-797
16. Levenson J, Flaud P, Del Pino M, Simon A: Blood viscosity as a
chronic contributing factor of vasodilation in humans. / Hypertens
1990;8:1049-1055
17. Gauss A: Gerinnungophysiologishe Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol 1957;17:237
18. Usami S, Chien S: Optical rcflectometry of red cell aggregation
under shear flow. BibI Ana: 1973;ll:91-97
19. Chien S: Rheology in the microcirculation in normal and low flow
states. Adv Shock Res 1982;8:71-80
20. Schmid-Schonbein H, Gallasch G, Volger E, Klose HJ: Microrheology and protein chemistry of pathological red cell aggregation
(blood sludge) studied in vitro. Biorheology 1973;10:213-227
21. Agosti R, D'Ettorre M, Cherubini P, divati A, Bozzoni M, Longhini E: On the hematocrit dependence of red blood cell aggregation, (abstract) Clin Hemorneol 1987;7:472
22. Pietsch L, Norris S, Haywood LJ, Meiselman HF: Hemorheological changes in patients with acute cardiogenic pulmonary edema,
(abstract) Clin Hemorheol 1987;7:432
23. Rainer C, Kawanishi DT, Chandraratna PAN, Bauersachs RM,
Reid CL, Rahimtoola SH, Meiselman HJ: Changes in blood rhe-
252
Hypertension
Vol 20, No 2 August 1992
ology in patients with stable angina pectoris as a result of coronary
artery disease. Circulation 1987;76:15-20
24. Chien S: Blood rheology in myocardial infarction and hypertension. Biorheology 1986;23:633-653
25. Laprcvote-Heuliy MC, Larcan A, Bollaert PE, Muller S, Donner M,
Streiff F, Stoltz JF: Hemorheological disturbances during thromboembolic states and various attacks. Clin HemorHeoi 1987;7:123-130
26. Chabanel A, Glacet Bernard A, Lelong F, Tacccoen A, Coscas G:
Increased red blood cell aggregation in retinal vein occlusion. Br J
Haanatol 1990;75:127-131
27. Williams BI, Gordon D, Peart WS: Abnormal variability of
intraocular pressure and systemic arterial blood pressure in diabetes, hypertension and retinal venous occlusion. Lancet 1981;2:
1255-1257
28. Simon A, Levenson J: Abnormal wall shear conditions in the
brachial artery of hypertensive patients. J Hypertens 1990;8:
109-114
29. Simon A, Flaud P, Levenson J: Pulsatile flow and oscillating wall
shear stress in the brachial artery of normotensive and hypertensive subjects. Cardiovasc Res 1990,2:129-136
Downloaded from http://hyper.ahajournals.org/ by guest on June 18, 2017
Increase in erythrocyte disaggregation shear stress in hypertension.
S M Razavian, M Del Pino, A Simon and J Levenson
Hypertension. 1992;20:247-252
doi: 10.1161/01.HYP.20.2.247
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