-Erythrocytes (red blood cells)-Leukocytes (white blood cells)-Thrombocytes (platelets) -Plasma (55-60% of volume): a). water (90-91%) b). proteins (6.5-8.5%) c). electrolytes, anions, etc.

Blood constituents

Determinants of blood viscosity

• RBC concentration (hematocrit)

• Plasma viscosity (Newtonian fluid)

• RBC deformability (at high hear rates)

• RBC aggregation (at low hear rates)

Normal (deformable) RBCsNormal (deformable) RBCs

Roggenkamp, et al., 1986Dr. Max Hardeman, with permission

Pathologies related to significantly increased RBC aggregation

• Cardiovascular diseases

• Diabetes

• Obesity

• Hypertension

• Atherosclerosis

• Shock

Methods of evaluation• Blood viscosity (viscometers; rheometers)• RBC deformability (asymptotic blood viscosity;

ektacytometry)• RBC aggregation (low shear blood viscosity,

erythrocyte sedimentation rate, aggregometers)

Results obtained by the most of these methods strongly depend on hematocrit

Ratio of male to female mortality due to myocardial Ratio of male to female mortality due to myocardial infarction, IHD, and cancer (Vital Statistics of the US) infarction, IHD, and cancer (Vital Statistics of the US)

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

10 20 30 40 50 60 70Age, years

Rat

io o

f m

orta

lity

Myocardial Infarction

IHD

Cancer

Hypotheses• The higher level of the circulating ovarian

hormones (estrogens) that produce a vasodilatory effect mediated by NO on coronary arteries protect women of reproductive age (however, the increase in risk of heart disease was found to be essentially the same in women with surgically induced menopause regardless of ovary removal)

• Our hypothesis was that rheological properties of the premenopausal female blood are optimized by a monthly blood loss to maximize gas transport

Correlation between hematocrit and blood pressure

Study of a large group of 17-18 years old teenagers (756 males and 705 females)

20

25

30

35

40

45

50

Males Females

Hematocrit

40

50

60

70

80

90

100

110

120

Males Females

Systolic BPDiastolic BP

Number of teenagers with elevated blood Number of teenagers with elevated blood pressure (above 140/85 mm Hg)pressure (above 140/85 mm Hg)

765

53

705

40

100

200

300

400

500

600

700

800

Num

ber o

f stu

dent

s

MalesMales FemalesFemales

Number of teenagers with elevated hematocrit Number of teenagers with elevated hematocrit (Ht>50%) in the hypertensive groups(Ht>50%) in the hypertensive groups

53 50

4 10

10

20

30

40

50

60

Num

ber

of s

tude

nts

MalesMales FemalesFemales

Effect of hematocrit on blood viscosity20% difference in Ht causes ~90% and ~40% difference in low and

high shear viscosity

0

20

40

60

80

100

0.01 0.1 1 10 100 1000

Shear rate (1/s)

Vis

cosi

ty (

cP)

Ht=40%

Ht=48%

Fåhraeus and Fåhraeus-Lindquist effectsReduction of RBC concentration and apparent viscosity in microvessels

(less than 0.5 mm diameter) due to development of the near-wall cell free layer and “plasma skimming” effect. The plasma layer increases the resistance for O2 diffusion and decreases vessel wall shear stresses.

0

20

40

60

80

100

120

Pres

sure

, mm

Hg

Aorta Arterioles CapillariesLarge

arteries and braches

Small arteries

RBC age distribution in male and female bloodRBC age distribution in male and female blood

0

10

20

30

40

50

60

Perc

ent

Young RBCs Middle age RBCs Old RBCs

MalesMales FemalesFemales

The picture is based on data published by Micheli et al. , 1984The picture is based on data published by Micheli et al. , 1984

Whole Whole bloodblood

CentrifugedCentrifuged

RBCsRBCs

Young RBCsYoung RBCs

Old RBCsOld RBCs

RBCsRBCs

PlasmPlasmaa

CentrifugedCentrifuged

0

20

40

60

80

100

120

140

160

180

200

"Young" RBCs "Old" RBCs

RBCRBCDeformabilityDeformability

RBCRBCSedimentationSedimentation

RateRate

Low Low ShearShear

ViscosityViscosity

RBCRBCMechanicalMechanical

FragilityFragility

p<0.05

p<0.001

p<0.05

p<0.001

Dif

fere

nce

(%

)

Mechanical properties of old and young red blood cellsMechanical properties of old and young red blood cells

Rheological parameters in male and premenopausal Rheological parameters in male and premenopausal female bloodfemale blood

Women

n=47

Men n=50

Level of statistical

significance

Age, years 25.7±4.8 26.2±5.1 n.s.

Hematocrit, % 40.0±2.4 45.8±2.7 p<0.001

Plasma viscosity, cP 1.73±0.09 1.74±0.08 n.s.

Low shear blood viscosity (0.277 s-1), cP Original hematocrit

35.2±4.8 55.4±11.1 p<0.001

Low shear blood viscosity (0.277 s-1), cP Standard hematocrit Ht=40%

35.59±3.73 41.7±4.3 p<0.001

Asymptotic Blood Viscosity, cP

Original hematocrit

4.8±0.4 5.9±0.5 p<0.001

Erythrocyte sedimentation rate, mm/hr Standard hematocrit Ht=40%

8.4±3.1

10.8±4.1

p=0.002

05

101520253035404550

Hem

atoc

rit,

%Difference in male (red) and female (green) hemorheological paraDifference in male (red) and female (green) hemorheological parametersmeters

p<0.001

50

60

70

80

90

100

110

RBC

def

orm

abili

ty, %

p<0.001

0

10

20

30

40

50

60

70

80

90

100

RB

C a

ggre

gatio

n,

diffe

renc

e (%

)

p<0.005

0

2

4

6

8

10

12

14

ESR

(mm

/hr)

p<0.01

Oxygen Delivery Index (hematocrit/blood viscosity )Oxygen Delivery Index (hematocrit/blood viscosity )

5

6

7

8

9

10

Male bloodFemale blood

p<0.001

Oxy

gen

Del

iver

y In

dex

Oxygen Delivery Index vs.Viscosity

2

3

4

5

6

7

8

9

10

15 20 25 30 35 40 45 50 55

Hematocrit, %

Vis

cosi

ty,

cP;

OD

I

Viscosity

ODI

3

4

5

6

7

8

9

10

35 40 45 50 55

Hematocrit, %

Blo

od v

isco

sity

(cP

); O

DI

Viscosity (women)ODI (women)Viscosity (men)ODI (men)

Asymptotic blood viscosity and oxygen delivery index Asymptotic blood viscosity and oxygen delivery index (ODI) vs. hematocrit for pre-menopausal women (ODI) vs. hematocrit for pre-menopausal women

(n=47) and age-matched men(n=47) and age-matched men (n= (n=50) 50)

ODI

5.0

6.0

7.0

8.0

9.0

Females (n=47) Males (n=50) Cardiac patients(n=15)

Ox

yg

en

De

live

ry In

de

xOxygen Delivery Index in premenopausal women,

men and cardiac patients

SummarySummary• Male blood has higher viscosity due to higher Male blood has higher viscosity due to higher

hematocrit and RBC aggregation and lower RBC hematocrit and RBC aggregation and lower RBC deformability deformability

• Men possess a higher number of old RBCs and a Men possess a higher number of old RBCs and a fewer number of young RBCs than premenopausal fewer number of young RBCs than premenopausal womenwomen

• Old RBCs demonstrate an increased ability to Old RBCs demonstrate an increased ability to aggregate and decreased deformability as aggregate and decreased deformability as compared to young RBCscompared to young RBCs

• Oxygen delivery index is significantly lower Oxygen delivery index is significantly lower (p<0.001) for male blood than for blood of pre-(p<0.001) for male blood than for blood of pre-menopausal femalesmenopausal females

• Increased blood viscosity and aggregability of Increased blood viscosity and aggregability of RBCs and decreased deformability of RBCs are RBCs and decreased deformability of RBCs are known risk factors of cardiovascular diseases.known risk factors of cardiovascular diseases.

• The difference in the mechanical properties of The difference in the mechanical properties of male and female blood places men at higher risk male and female blood places men at higher risk of cardiovascular diseases than pre-menopausal of cardiovascular diseases than pre-menopausal womenwomen

• Blood donation or regular, small phlebotomy Blood donation or regular, small phlebotomy might help to improve rheological properties of might help to improve rheological properties of blood and reduce the risk of cardiovascular blood and reduce the risk of cardiovascular diseases in men and post-menopausal womendiseases in men and post-menopausal women

Summary (cont.)Summary (cont.)

RBC aggregation promotes a formation of the near-wall plasma layer in microvessels reducing wall shear stresses, shear-induced vasodilation and

intracapillary hematocrit.

Due to exercises, increased blood flow decreases RBC aggregation and, thus, reduces the near wall plasma layer and plasma skimming at bifurcations. This leads to an increase in wall shear stresses, vasodilation, number of functioning capillaries, and concentration of RBCs in capillaries enhancing delivery of O2

and removal of metabolites.

w w

Effect of exercises on RBC aggregation and microcirculation

References• Micheli V, Taddeo A, Vanni AL, Pecciarini L, Massone M and Ricci MG. Distribuzione

in gradiente di densita’ degli eritrociti umani: differenze lagate al sesso, Boll. Soc. Italiana Biol. Speriment. LX(3) (1984), 665–671.

• Kameneva MV and Timofeev VF. Increased hematocrit as a risk factor for arterial hypertension. Cardiologiya 10 (1986), 105–106.

• Lowe GDO, editor. Clinical Blood Rheology. CRC Press, Boca Raton, Florida, 1988.• Vital Statistics of the United States 1990, Vol. 2, Mortality, U.S. Department of Health

and Human Services, Hyattsville, MD, 1994.• Kameneva MV. Effect of hematocrit on the development and consequences of some

hemodynamic disorders. In: "Contemporary Problems of Biomechanics," GG Chernyi and SA Regirer, (eds.). Mir. Publ., Moscow, USSR, CRC Press, Boca Raton, 1990, 111-26.

• Meyers DC, Strickland D, Maloley PA, Seburg JJ, Wilson JE and McManus BF. Possible association of a reduction in cardiovascular events with blood donation, Heart 78(2) (1997), 188–193.

• Kameneva MV, Garrett KO, Watach MJ, and Borovetz HS. Red blood cell aging and risk of cardiovascular diseases. Clinical Hemorheology and Microcirculation, 18(1):67-74, 1998.

• Kameneva MV, Watach MJ, and Borovetz HS. Gender difference in rheologic properties of blood and risk of cardiovascular diseases. Clinical Hemorheology and Microcirculation, 21(3-4):357-363, 1999.

• Kameneva MV, Watach MJ, and Borovetz HS. Rheologic dissimilarities in female and male blood: potential link to development of cardiovascular diseases. In: Advances in Experimental Medicine & Biology. Oxygen Transport to Tissue XXIV. JF Dunn and HM Swartz (Eds.), Kluwer Academic/Plenum Publisher, New York, 2003, vol. 530, pp 689-696.

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