- Email: [email protected]
Effect of hematocrit on blood pressure via hyperviscosity
AJH
1999;12:739 –743
BRIEF COMMUNICATIONS
Effect of Hematocrit on Blood Pressure Via Hyperviscosity Yıldırım C¸ınar, Gamze Demı˙r, Mustafa Pac¸, and Ays¸e Bas¸ak C¸ınar
Increase in blood viscosity, defined as resistance to flow, is one factor in hypertension and atherosclerosis that contributes to the morbidity and mortality associated with tissue ischemia. In this research we evaluated the effect of hematocrit on increasing viscosity, and possible related changes in blood pressure, flow rate, and the equivalent physiologic compensation ratios. Blood samples were taken from 32 healthy individuals and centrifuged for 5 min at 3000 rpm to obtain 2.5 mL of erythrocyte mass from each. Then, at each step 0.5 mL of plasma was consecutively added in a total of 17 steps. The resultant hematocrit and viscosity changes were measured. Viscosity measurement was performed by capillary viscometer. The results were evaluated by the Student t test. It was observed that in the range of 60.16% and 25.32%, a 10.99% increase of hematocrit
B
lood viscosity means the resistance of blood tissue against flow. Practically speaking, viscosity is the total of friction between molecules, cells, and the lumen. The simplest way of measuring viscosity is based on Poiseuille’s law.1,2 The velocity is formulated as v 5 1/4hL (F1 2 F2)(a 2 2 r2) per sec, thus F1, F2 are the initial and final crosssectional pressures on a cylinder of fluid, length L and coefficient of viscosity h, distance r from the center of pipe, the radius of pipe being a. According to this equation, the flow time is directly proportional to the
Received May 21, 1998. Accepted November 30, 1998. From the Haydarpas¸a Numune Hospital, Istanbul, Turkey Address reprint requests and correspondence to Assoc. Prof. Yıldırım C ¸ ınar, MD, PK 13 Kadıko¨y, 81301, Istanbul, Turkey; e-mail: [email protected]
© 1999 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
produced an increase of 1 unit relative viscosity, which means approximately a 20% increase in blood viscosity for a healthy individual. According to Poiseuille’s equation, with a constant vessel length, if viscosity is increased by 20%, the decrease in blood flow rate will be 16.67% (100/120 5 83.33%; 100 2 83.33 5 16.67%). For the physiologic compensation of 20% increased viscosity, blood pressure increase will be 20% or vasodilation will be 4.66% in radius. Atherosclerotic and some healthy vessels with little vasodilatory capacities might benefit from treatment modalities to decrease the viscosity by hemodilution. Am J Hypertens 1999;12:739 –743 © 1999 American Journal of Hypertension, Ltd. KEY WORDS:
Hyperviscosity, hematocrit, hypertension, circulatory load.
pressure difference between the two ends of tube (F1 2 F2) and inversely proportional to the length L of the tube and the viscosity. These are known as Poiseuille’s law. This equation provides the calculation of flow rate Q in m3/sec: Q 5 pa 4/8 hL (F1 2 F2). According to this equation, a decrease in viscosity causes an increase in cardiac output and opposite this, an increase in viscosity causes a decrease in cardiac output. Therefore, the physiologic compensation of viscosity-related decreased blood flow rate will be an increase in pressure or vasodilation. For the measurement of viscosity, capillary tubes are the most commonly and practically used.2– 4 The measurement is based on the comparison of the blood flow time with distilled water’s flow time under the same conditions by means of its volume, temperature, and pressure. If the flow time of distilled water is 0895-7061/99/$20.00 PII S0895-7061(99)00011-4
740
AJH–JULY 1999 –VOL. 12, NO. 7
C ¸ INAR ET AL
accepted as 1, then the values achieved by comparison may be termed as “relative viscosity.” These values are 1.4 to 1.8 for serum, 1.7 to 2.2 for plasma, and 2.5 to 4 for blood.2,3,5 Determined viscosity factors for blood are erythrocyte and leukocyte masses, plasma fibrinogen, the structure and amount of proteins, internal viscosity, and deformability of erythrocytes.6 – 8 It is reported that blood viscosity can be a factor in the physiopathology of hypertension, left ventricle hypertrophy, and ischemic heart diseases.9 –13 METHODS A total of 32 healthy subjects who had no medical complaints and had not taken any medication for at least 1 week were chosen randomly and informed consent was obtained. In the morning, after a 12-h fasting period, 20 mL blood from the brachial vein of each subject was taken with a syringe containing 0.2 mL heparin. These blood samples were centrifuged at 3000 rpm for 5 min to separate the plasma and erythrocyte mass. In the next step, the hematocrit values and the viscosity of the erythrocyte mass were measured. Following this, 0.5 mL of the separated plasma was added at each step onto 2.5 mL of erythrocyte mass and blood viscosity measurement was repeated. As a result, a total of 17 hemodilution steps were performed consecutively for each case. Viscosity Measurement The upper part of the measurement line of glass laboratory pipette with 0.1-mL capacity was heated and then blown to form a reservoir with a volume of 2 mL. With a diamond pen, the top and bottom borders of the reservoir were marked and the pipette used as a capillary viscometer. The pipette was filled with liquid until the upper borderline of the reservoir and the flow time of the fluid to the lower line was measured (in seconds) and used for the calculation of relative viscosity. To perform accurate measurements, the same viscometer was used at a constant temperature, without the effect of direct sunlight, in the same vertical position and in a place where there was no air flow. Before each assay, standardization measurements were performed with distilled water. The temperatures of blood, viscometer, and distilled water were balanced with the laboratory temperature. To prevent protein precipitation, the viscometer was washed with 0.9% NaCl and then with distilled water, and finally dried with acetone. After each cleaning procedure and before the measurement of following sample, calibration procedures were conducted with distilled water and all measurements were repeated three times to get the mean value as a result. The values were calculated as relative viscosity. The statistical evaluation was performed with the Student t test.
TABLE 1. HEMATOCRIT AND VISCOSITY CHANGES RELATED TO HEMODILUTION WITH THE ADDITION OF 0.5 ML OF PLASMA AT 17 CONSECUTIVE STEPS, STARTING FROM AN INITIAL ERYTHROCYTE MASS OF 2.5 ML Total Added Plasma Volume (mL)
Mean Hematocrit (%)
Mean Relative Viscosity
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5
84.12 6 0.49 79.93 6 0.51 67.84 6 0.50 60.16 6 0.58 56.16 6 0.37 53.80 6 0.40 47.35 6 0.48 39.03 6 0.40 37.96 6 0.40 37.51 6 0.50 36.67 6 0.47 35.48 6 0.81 33.61 6 0.49 31.93 6 0.44 30.03 6 0.31 28.83 6 0.37 26.83 6 0.37 25.32 6 0.47
18.01 6 0.03 11.24 6 0.05 8.73 6 0.05 6.79 6 0.04 5.99 6 0.04 5.44 6 0.07 5.09 6 0.03 4.75 6 0.05 4.48 6 0.04 4.34 6 0.05 4.19 6 0.01 4.11 6 0.04 3.91 6 0.03 3.85 6 0.05 3.80 6 0.03 3.78 6 0.04 3.67 6 0.04 3.62 6 0.04
RESULTS The blood samples from each of the 32 subjects were centrifuged separately for 5 min at 3000 rpm. The initial mean of hematocrit value of erythrocyte mass was found to be 84.12%. The changes in hematocrit as well as viscosity values by plasma dilution in 17 steps are shown in Table 1. With each dilution step, the hematocrit value obtained was statistically different from the initial value, but it was also different from the values of the previous and following steps (P ,.001). The same relationships existed for viscosity as well (P ,.001). The relationship between hematocrit and viscosity is shown in Figure 1. The hematocrit value was initially 84.12% and was 25.32% at the end of the seventeenth dilution step; the difference between the hematocrit values was 58.8%. The relative viscosity values of the same hematocrit range and the difference were calculated as: 18.0 2 3.62 5 14.39, respectively. These results suggest that for every 4.8 rise in hematocrit value, there is a 1 unit increase in relative viscosity measurement (58.8% 2 25.32% hematocrit/ 18.01 2 3.12 viscosity 5 4.08%). If the same 1 unit viscosity values are calculated in the range where there is a partial linear correlation, they are found to be: 60.16% 2 25.32% hematocrit/6.79 2 3.62 viscosity 5 10.99%.
AJH–JULY 1999 –VOL. 12, NO. 7
HEMATOCRIT, HYPERVISCOSITY, AND BLOOD PRESSURE
741
FIGURE 1. Decrease in hematocrit levels resulting from the addition of 0.5 mL of plasma at 17 consecutive steps onto 2.5 mL of erythrocyte mass causes a significant decrease in viscosity at each step (P ,.001).
DISCUSSION In view of the articles in the literature about the treatment of ischemia caused by hyperviscosity, it is possible to summarize that the treatment is based on hemodilution, decreasing erythrocyte mass, and filtration of fibrinogen or other paraproteins and treatment of underlying disease.14 –17 There is a limited amount of literature that reports a temporary decrease in blood viscosity caused by the effects of medication.18,20 In Figure 1, the linear correlation between physiologic ranges of hematocrit and viscosity is shown. In terms of hematocrit values close to physiologic conditions in which a different correlation exists, for every 10.99% rise in the hematocrit level, there is a 1 unit relative viscosity increase. Because the mean relative viscosity level is 5.09 for 47.35% hematocrit value as seen on Table 1 and it is accepted as normal, the 1 unit relative viscosity increase is approximately equal to a 20% difference (1/5.09 > 20%). According to Poiseuille’s equation, Q 5 pa4/8 hL (F1 2 F2); a 20% increase in viscosity leads to a 16.67% reduction in blood flow rate. If the denominator is considered to be 120 instead of 100, blood flow rate is calculated to be 100/120 5 83.33%, so the reduction is 100 2 83.33 5 16.67%. According to the same equation, a reduction in viscosity will increase the value of Q. A 20% increased viscosity, represented in the denominator, is expected to increase the difference in pressure (F1 2 F2) 20% to keep the constant blood flow rate Q. As a result, to physiologically compensate for the 10.59% increased hematocrit and related 20% increased viscosity, which is causing the 16.67% decreased blood flow rate, it is necessary to have either a 20% increase in blood pressure or a 4.66% vasodilation
FIGURE 2. To physiologically compensate for the 10.59% increased hematocrit and the related 20% increased viscosity that is causing the 16.67% decreased blood flow rate, it is necessary to have either a 20% increase in blood pressure or a 4.66% vasodilation in radius.
in radius a as: a 4final 5 1.2 3 a 4initial; a final 5 Î4 1.2 3 a initial 5 1.0466 3 a initial; if, a initial 5 100; a final 2 a initial 5 4.66 and these relations are presented in Figure 2 as a flow chart. In many studies, it is reported that atherosclerotic vessels and even some normal vessels do not have the vasodilation capacity and, furthermore, they do not respond to vasodilator drug therapy. Feldman et al performed a study in which 150 mm intracoronary nitroglycerin caused 34% vasodilation in the left coronary distal segment, 38% in collateral arteries, 54% in small coronary arteries, and only 5% in the atherosclerotic coronary arteries. These studies lead to the notion that it is more beneficial to have a decrease in viscosity instead of vasodilation in patients with atherosclerotic arteries, because these vessels not only
742
AJH–JULY 1999 –VOL. 12, NO. 7
C ¸ INAR ET AL
have an impaired response to the physiologic compensatory vasodilation needed but also to vasodilator medications.21,26 Haghighat et al have shown that agoraphobia and brain ischemia can be normalized by hemodilution and aspirin.15 Cole et al have revealed that brain infarct area as a result of ischemia can be reduced by hemodilution.16 This research provides important supporting evidence of the propositions suggested in this study. Although clinically prominent hyperviscosity syndromes are reported, there are no sufficient data about the prevalence of milder forms and their long term effects. For example, policythemia may be classified as hyperviscosity syndrome.27 The place where blood flow is mostly affected by viscosity is the capillary bed, which has a narrower diameter than erythrocytes. Therefore, there is a risk of hypotension and stasis in this area if vasodilation is used for increasing the blood flow rate. Compensatory blood pressure increase may constitute an extra circulatory work load and a provocation of hypertension, so it seems better in patients with atherosclerosis, hypertension, and ischemia to increase blood flow rate by decreasing viscosity. In conclusion, a lowered blood viscosity level may constitute a lesser blood pressure, friction and damage on the vessel lumen, and it may slow the atherosclerotic process. Therefore, additional studies probably will lead to further biologic and medical advantages. REFERENCES 1.
Poiseuille M: Recherches experimentales sur le mouvement des liquids dans les tubes de tre´s petits diametres. Des Seances de L’Acade´mie des Sciences 1841;11:961– 967;1041–1048.
2.
Williams WJ: Serum Viscosity, in Beutler E, Lichtman MA, Coller BS, Kipps TJ (eds): Williams Hematology, Fifth Ed. McGraw-Hill, New York, 1995, pp L81–L82.
3.
Kjeldsberg CR: Principles of hematologic examination, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth Ed. Lea and Febiger, Philadelphia, 1993, pp 7–37.
4.
Foerster J: Plasma Cell Dyscrasias, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth ed. Lea and Febiger, Philadelphia, 1993, pp 2202–2218.
5.
Fuchs J, Weinberger I, Rotenberg Z, et al: Plasma viscosity in ischemic heart disease. Am Heart J 1984;108: 435– 439.
6.
Fahey JL, Barth WF, Solomon A: Serum hyperviscosity syndrome. JAMA 1965;192:467– 467.
7.
Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, Elwood PC: Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991;83:836 – 844.
8.
C ¸ ınar Y, Demir G, C ¸ ınar B, Pac¸ M: Different fat metabolism in chronic renal failure and fat loading hyperviscosity related circulatory load. Am J Kidney Dis 1998; 31:A12.
9.
Hossmann V, Bo¨nner G, Wambach G, Laaser U, Kaufman W: Blood viscosity: a pathogenic factor in the development of essential hypertension? Clin Exp Hypertens (A) 1986;8:673– 680.
10.
Devereux RB, Drayer JI, Chien S, Pickering TG, Letcher RL, De Young JL, Sealey JG, Laragh JH: Whole blood viscosity as a determinant of cardiac hypertrophy in systemic hypertension. Am J Cardiol 1984;54:592–595.
11.
Yarnell JWG, Sweetnam PM, Hutton RD, Davies ME, Elswood PC: Plasma and whole blood viscosity in ischemic heart disease: The Caerphilly Studies. Clin Hemorheol 1988;8:501–506.
12.
Koenig W, Sund M, Ernst E, Keil U, Rosenthal J, Hombach V: Association between plasma viscosity and blood pressure. Results from the MONICA-Project Ausburg. Am J Hypertens 1991;4:529 –536.
13.
Ernst E, Koenig W, Matrai A, Keil U: Plasma viscosity and hemoglobin in the presence of cardiovascular risk factor. Clin Hemorheol 1988;:507–515.
14.
Mueller R. On the therapy of disturbance of blood fluidity. Angiology 1985;36:226 –234.
15.
Haghighat R, Costa DC, Chesser E: Polycythaemia and agoraphobia. J Behav Ther Exp Psychiatry 1996;27:149 – 155.
16.
Cole DJ, Drummond JC, Patel PM, Reynolds LR: Hypervolemic hemodilution during cerebral ischemia in rats: effect of diaspirin cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume. J Neurosurg Anesthesiol 1997;9:44 –50.
17.
Spahn DR, Schmid ER, Seifert B, Pasch T: Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy. Anesth Analg 1996;82:687– 694.
18.
Weinberger I, Fuchs J, Rotenberg Z, Rappoport M, Agmon J: The acute effect of sublingual nifedipine and isosorbite dinitrate on plasma viscosity in patients with acute myocardial infarction. Clin Cardiol 1986;9:556 – 560.
19.
Gousios A, Martin A, Shearn MD: Effect of intravenous heparin on human blood viscosity. Circulation 1959;20: 1063–1066.
20.
Vojnikovic B: Doxium (calcium dobesilate) reduces blood hyperviscosity and lowers elevated intraocular pressure in patients with diabetic retinopathy and glaucoma. Ophthal Res 1991;23:12–20.
21.
Cannon RO III, Schenke WH, Leon MB, Rosing DR, Urqhart J, Epstein SE: Limited coronary flow reserve after dipyridamole in patients with ergonovine-induced coronary vasoconstriction. Circulation 1987;75: 163–174.
22.
Marcus ML, Doty DB, Hiratzka LF, Wright CB, Eastham CL: Decreased coronary reserve: a mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries. N Engl J Med 1982;307:1362– 1366.
23.
Hoffman JI: A critical view of coronary reserve. Circulation 1987;75:11–16.
AJH–JULY 1999 –VOL. 12, NO. 7
24.
25.
HEMATOCRIT, HYPERVISCOSITY, AND BLOOD PRESSURE
Cannon RO III, Bonow RO, Bacharach SL, Green MW, Rosing DR, Leon MB, Watson RM, Epstein SE: Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation 1985;71:218 –226. Hintze TH, Vatner SF: Reactive dilation of large coronary arteries in conscious dogs. Circ Res 1984;54:50 –57.
743
26.
Feldman RL, Marx JD, Pepine CJ, Conti CR: Analysis of coronary responses to various doses of intracoronary nitroglycerin. Circulation 1982;66:321–327.
27.
Athens JW: Polycytemia Vera, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth Ed. Lea and Febiger; Philadelphia, 1993, pp 1999 –2017.
1999;12:739 –743
BRIEF COMMUNICATIONS
Effect of Hematocrit on Blood Pressure Via Hyperviscosity Yıldırım C¸ınar, Gamze Demı˙r, Mustafa Pac¸, and Ays¸e Bas¸ak C¸ınar
Increase in blood viscosity, defined as resistance to flow, is one factor in hypertension and atherosclerosis that contributes to the morbidity and mortality associated with tissue ischemia. In this research we evaluated the effect of hematocrit on increasing viscosity, and possible related changes in blood pressure, flow rate, and the equivalent physiologic compensation ratios. Blood samples were taken from 32 healthy individuals and centrifuged for 5 min at 3000 rpm to obtain 2.5 mL of erythrocyte mass from each. Then, at each step 0.5 mL of plasma was consecutively added in a total of 17 steps. The resultant hematocrit and viscosity changes were measured. Viscosity measurement was performed by capillary viscometer. The results were evaluated by the Student t test. It was observed that in the range of 60.16% and 25.32%, a 10.99% increase of hematocrit
B
lood viscosity means the resistance of blood tissue against flow. Practically speaking, viscosity is the total of friction between molecules, cells, and the lumen. The simplest way of measuring viscosity is based on Poiseuille’s law.1,2 The velocity is formulated as v 5 1/4hL (F1 2 F2)(a 2 2 r2) per sec, thus F1, F2 are the initial and final crosssectional pressures on a cylinder of fluid, length L and coefficient of viscosity h, distance r from the center of pipe, the radius of pipe being a. According to this equation, the flow time is directly proportional to the
Received May 21, 1998. Accepted November 30, 1998. From the Haydarpas¸a Numune Hospital, Istanbul, Turkey Address reprint requests and correspondence to Assoc. Prof. Yıldırım C ¸ ınar, MD, PK 13 Kadıko¨y, 81301, Istanbul, Turkey; e-mail: [email protected]
© 1999 by the American Journal of Hypertension, Ltd. Published by Elsevier Science, Inc.
produced an increase of 1 unit relative viscosity, which means approximately a 20% increase in blood viscosity for a healthy individual. According to Poiseuille’s equation, with a constant vessel length, if viscosity is increased by 20%, the decrease in blood flow rate will be 16.67% (100/120 5 83.33%; 100 2 83.33 5 16.67%). For the physiologic compensation of 20% increased viscosity, blood pressure increase will be 20% or vasodilation will be 4.66% in radius. Atherosclerotic and some healthy vessels with little vasodilatory capacities might benefit from treatment modalities to decrease the viscosity by hemodilution. Am J Hypertens 1999;12:739 –743 © 1999 American Journal of Hypertension, Ltd. KEY WORDS:
Hyperviscosity, hematocrit, hypertension, circulatory load.
pressure difference between the two ends of tube (F1 2 F2) and inversely proportional to the length L of the tube and the viscosity. These are known as Poiseuille’s law. This equation provides the calculation of flow rate Q in m3/sec: Q 5 pa 4/8 hL (F1 2 F2). According to this equation, a decrease in viscosity causes an increase in cardiac output and opposite this, an increase in viscosity causes a decrease in cardiac output. Therefore, the physiologic compensation of viscosity-related decreased blood flow rate will be an increase in pressure or vasodilation. For the measurement of viscosity, capillary tubes are the most commonly and practically used.2– 4 The measurement is based on the comparison of the blood flow time with distilled water’s flow time under the same conditions by means of its volume, temperature, and pressure. If the flow time of distilled water is 0895-7061/99/$20.00 PII S0895-7061(99)00011-4
740
AJH–JULY 1999 –VOL. 12, NO. 7
C ¸ INAR ET AL
accepted as 1, then the values achieved by comparison may be termed as “relative viscosity.” These values are 1.4 to 1.8 for serum, 1.7 to 2.2 for plasma, and 2.5 to 4 for blood.2,3,5 Determined viscosity factors for blood are erythrocyte and leukocyte masses, plasma fibrinogen, the structure and amount of proteins, internal viscosity, and deformability of erythrocytes.6 – 8 It is reported that blood viscosity can be a factor in the physiopathology of hypertension, left ventricle hypertrophy, and ischemic heart diseases.9 –13 METHODS A total of 32 healthy subjects who had no medical complaints and had not taken any medication for at least 1 week were chosen randomly and informed consent was obtained. In the morning, after a 12-h fasting period, 20 mL blood from the brachial vein of each subject was taken with a syringe containing 0.2 mL heparin. These blood samples were centrifuged at 3000 rpm for 5 min to separate the plasma and erythrocyte mass. In the next step, the hematocrit values and the viscosity of the erythrocyte mass were measured. Following this, 0.5 mL of the separated plasma was added at each step onto 2.5 mL of erythrocyte mass and blood viscosity measurement was repeated. As a result, a total of 17 hemodilution steps were performed consecutively for each case. Viscosity Measurement The upper part of the measurement line of glass laboratory pipette with 0.1-mL capacity was heated and then blown to form a reservoir with a volume of 2 mL. With a diamond pen, the top and bottom borders of the reservoir were marked and the pipette used as a capillary viscometer. The pipette was filled with liquid until the upper borderline of the reservoir and the flow time of the fluid to the lower line was measured (in seconds) and used for the calculation of relative viscosity. To perform accurate measurements, the same viscometer was used at a constant temperature, without the effect of direct sunlight, in the same vertical position and in a place where there was no air flow. Before each assay, standardization measurements were performed with distilled water. The temperatures of blood, viscometer, and distilled water were balanced with the laboratory temperature. To prevent protein precipitation, the viscometer was washed with 0.9% NaCl and then with distilled water, and finally dried with acetone. After each cleaning procedure and before the measurement of following sample, calibration procedures were conducted with distilled water and all measurements were repeated three times to get the mean value as a result. The values were calculated as relative viscosity. The statistical evaluation was performed with the Student t test.
TABLE 1. HEMATOCRIT AND VISCOSITY CHANGES RELATED TO HEMODILUTION WITH THE ADDITION OF 0.5 ML OF PLASMA AT 17 CONSECUTIVE STEPS, STARTING FROM AN INITIAL ERYTHROCYTE MASS OF 2.5 ML Total Added Plasma Volume (mL)
Mean Hematocrit (%)
Mean Relative Viscosity
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5
84.12 6 0.49 79.93 6 0.51 67.84 6 0.50 60.16 6 0.58 56.16 6 0.37 53.80 6 0.40 47.35 6 0.48 39.03 6 0.40 37.96 6 0.40 37.51 6 0.50 36.67 6 0.47 35.48 6 0.81 33.61 6 0.49 31.93 6 0.44 30.03 6 0.31 28.83 6 0.37 26.83 6 0.37 25.32 6 0.47
18.01 6 0.03 11.24 6 0.05 8.73 6 0.05 6.79 6 0.04 5.99 6 0.04 5.44 6 0.07 5.09 6 0.03 4.75 6 0.05 4.48 6 0.04 4.34 6 0.05 4.19 6 0.01 4.11 6 0.04 3.91 6 0.03 3.85 6 0.05 3.80 6 0.03 3.78 6 0.04 3.67 6 0.04 3.62 6 0.04
RESULTS The blood samples from each of the 32 subjects were centrifuged separately for 5 min at 3000 rpm. The initial mean of hematocrit value of erythrocyte mass was found to be 84.12%. The changes in hematocrit as well as viscosity values by plasma dilution in 17 steps are shown in Table 1. With each dilution step, the hematocrit value obtained was statistically different from the initial value, but it was also different from the values of the previous and following steps (P ,.001). The same relationships existed for viscosity as well (P ,.001). The relationship between hematocrit and viscosity is shown in Figure 1. The hematocrit value was initially 84.12% and was 25.32% at the end of the seventeenth dilution step; the difference between the hematocrit values was 58.8%. The relative viscosity values of the same hematocrit range and the difference were calculated as: 18.0 2 3.62 5 14.39, respectively. These results suggest that for every 4.8 rise in hematocrit value, there is a 1 unit increase in relative viscosity measurement (58.8% 2 25.32% hematocrit/ 18.01 2 3.12 viscosity 5 4.08%). If the same 1 unit viscosity values are calculated in the range where there is a partial linear correlation, they are found to be: 60.16% 2 25.32% hematocrit/6.79 2 3.62 viscosity 5 10.99%.
AJH–JULY 1999 –VOL. 12, NO. 7
HEMATOCRIT, HYPERVISCOSITY, AND BLOOD PRESSURE
741
FIGURE 1. Decrease in hematocrit levels resulting from the addition of 0.5 mL of plasma at 17 consecutive steps onto 2.5 mL of erythrocyte mass causes a significant decrease in viscosity at each step (P ,.001).
DISCUSSION In view of the articles in the literature about the treatment of ischemia caused by hyperviscosity, it is possible to summarize that the treatment is based on hemodilution, decreasing erythrocyte mass, and filtration of fibrinogen or other paraproteins and treatment of underlying disease.14 –17 There is a limited amount of literature that reports a temporary decrease in blood viscosity caused by the effects of medication.18,20 In Figure 1, the linear correlation between physiologic ranges of hematocrit and viscosity is shown. In terms of hematocrit values close to physiologic conditions in which a different correlation exists, for every 10.99% rise in the hematocrit level, there is a 1 unit relative viscosity increase. Because the mean relative viscosity level is 5.09 for 47.35% hematocrit value as seen on Table 1 and it is accepted as normal, the 1 unit relative viscosity increase is approximately equal to a 20% difference (1/5.09 > 20%). According to Poiseuille’s equation, Q 5 pa4/8 hL (F1 2 F2); a 20% increase in viscosity leads to a 16.67% reduction in blood flow rate. If the denominator is considered to be 120 instead of 100, blood flow rate is calculated to be 100/120 5 83.33%, so the reduction is 100 2 83.33 5 16.67%. According to the same equation, a reduction in viscosity will increase the value of Q. A 20% increased viscosity, represented in the denominator, is expected to increase the difference in pressure (F1 2 F2) 20% to keep the constant blood flow rate Q. As a result, to physiologically compensate for the 10.59% increased hematocrit and related 20% increased viscosity, which is causing the 16.67% decreased blood flow rate, it is necessary to have either a 20% increase in blood pressure or a 4.66% vasodilation
FIGURE 2. To physiologically compensate for the 10.59% increased hematocrit and the related 20% increased viscosity that is causing the 16.67% decreased blood flow rate, it is necessary to have either a 20% increase in blood pressure or a 4.66% vasodilation in radius.
in radius a as: a 4final 5 1.2 3 a 4initial; a final 5 Î4 1.2 3 a initial 5 1.0466 3 a initial; if, a initial 5 100; a final 2 a initial 5 4.66 and these relations are presented in Figure 2 as a flow chart. In many studies, it is reported that atherosclerotic vessels and even some normal vessels do not have the vasodilation capacity and, furthermore, they do not respond to vasodilator drug therapy. Feldman et al performed a study in which 150 mm intracoronary nitroglycerin caused 34% vasodilation in the left coronary distal segment, 38% in collateral arteries, 54% in small coronary arteries, and only 5% in the atherosclerotic coronary arteries. These studies lead to the notion that it is more beneficial to have a decrease in viscosity instead of vasodilation in patients with atherosclerotic arteries, because these vessels not only
742
AJH–JULY 1999 –VOL. 12, NO. 7
C ¸ INAR ET AL
have an impaired response to the physiologic compensatory vasodilation needed but also to vasodilator medications.21,26 Haghighat et al have shown that agoraphobia and brain ischemia can be normalized by hemodilution and aspirin.15 Cole et al have revealed that brain infarct area as a result of ischemia can be reduced by hemodilution.16 This research provides important supporting evidence of the propositions suggested in this study. Although clinically prominent hyperviscosity syndromes are reported, there are no sufficient data about the prevalence of milder forms and their long term effects. For example, policythemia may be classified as hyperviscosity syndrome.27 The place where blood flow is mostly affected by viscosity is the capillary bed, which has a narrower diameter than erythrocytes. Therefore, there is a risk of hypotension and stasis in this area if vasodilation is used for increasing the blood flow rate. Compensatory blood pressure increase may constitute an extra circulatory work load and a provocation of hypertension, so it seems better in patients with atherosclerosis, hypertension, and ischemia to increase blood flow rate by decreasing viscosity. In conclusion, a lowered blood viscosity level may constitute a lesser blood pressure, friction and damage on the vessel lumen, and it may slow the atherosclerotic process. Therefore, additional studies probably will lead to further biologic and medical advantages. REFERENCES 1.
Poiseuille M: Recherches experimentales sur le mouvement des liquids dans les tubes de tre´s petits diametres. Des Seances de L’Acade´mie des Sciences 1841;11:961– 967;1041–1048.
2.
Williams WJ: Serum Viscosity, in Beutler E, Lichtman MA, Coller BS, Kipps TJ (eds): Williams Hematology, Fifth Ed. McGraw-Hill, New York, 1995, pp L81–L82.
3.
Kjeldsberg CR: Principles of hematologic examination, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth Ed. Lea and Febiger, Philadelphia, 1993, pp 7–37.
4.
Foerster J: Plasma Cell Dyscrasias, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth ed. Lea and Febiger, Philadelphia, 1993, pp 2202–2218.
5.
Fuchs J, Weinberger I, Rotenberg Z, et al: Plasma viscosity in ischemic heart disease. Am Heart J 1984;108: 435– 439.
6.
Fahey JL, Barth WF, Solomon A: Serum hyperviscosity syndrome. JAMA 1965;192:467– 467.
7.
Yarnell JWG, Baker IA, Sweetnam PM, Bainton D, O’Brien JR, Whitehead PJ, Elwood PC: Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991;83:836 – 844.
8.
C ¸ ınar Y, Demir G, C ¸ ınar B, Pac¸ M: Different fat metabolism in chronic renal failure and fat loading hyperviscosity related circulatory load. Am J Kidney Dis 1998; 31:A12.
9.
Hossmann V, Bo¨nner G, Wambach G, Laaser U, Kaufman W: Blood viscosity: a pathogenic factor in the development of essential hypertension? Clin Exp Hypertens (A) 1986;8:673– 680.
10.
Devereux RB, Drayer JI, Chien S, Pickering TG, Letcher RL, De Young JL, Sealey JG, Laragh JH: Whole blood viscosity as a determinant of cardiac hypertrophy in systemic hypertension. Am J Cardiol 1984;54:592–595.
11.
Yarnell JWG, Sweetnam PM, Hutton RD, Davies ME, Elswood PC: Plasma and whole blood viscosity in ischemic heart disease: The Caerphilly Studies. Clin Hemorheol 1988;8:501–506.
12.
Koenig W, Sund M, Ernst E, Keil U, Rosenthal J, Hombach V: Association between plasma viscosity and blood pressure. Results from the MONICA-Project Ausburg. Am J Hypertens 1991;4:529 –536.
13.
Ernst E, Koenig W, Matrai A, Keil U: Plasma viscosity and hemoglobin in the presence of cardiovascular risk factor. Clin Hemorheol 1988;:507–515.
14.
Mueller R. On the therapy of disturbance of blood fluidity. Angiology 1985;36:226 –234.
15.
Haghighat R, Costa DC, Chesser E: Polycythaemia and agoraphobia. J Behav Ther Exp Psychiatry 1996;27:149 – 155.
16.
Cole DJ, Drummond JC, Patel PM, Reynolds LR: Hypervolemic hemodilution during cerebral ischemia in rats: effect of diaspirin cross-linked hemoglobin (DCLHb) on neurologic outcome and infarct volume. J Neurosurg Anesthesiol 1997;9:44 –50.
17.
Spahn DR, Schmid ER, Seifert B, Pasch T: Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy. Anesth Analg 1996;82:687– 694.
18.
Weinberger I, Fuchs J, Rotenberg Z, Rappoport M, Agmon J: The acute effect of sublingual nifedipine and isosorbite dinitrate on plasma viscosity in patients with acute myocardial infarction. Clin Cardiol 1986;9:556 – 560.
19.
Gousios A, Martin A, Shearn MD: Effect of intravenous heparin on human blood viscosity. Circulation 1959;20: 1063–1066.
20.
Vojnikovic B: Doxium (calcium dobesilate) reduces blood hyperviscosity and lowers elevated intraocular pressure in patients with diabetic retinopathy and glaucoma. Ophthal Res 1991;23:12–20.
21.
Cannon RO III, Schenke WH, Leon MB, Rosing DR, Urqhart J, Epstein SE: Limited coronary flow reserve after dipyridamole in patients with ergonovine-induced coronary vasoconstriction. Circulation 1987;75: 163–174.
22.
Marcus ML, Doty DB, Hiratzka LF, Wright CB, Eastham CL: Decreased coronary reserve: a mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries. N Engl J Med 1982;307:1362– 1366.
23.
Hoffman JI: A critical view of coronary reserve. Circulation 1987;75:11–16.
AJH–JULY 1999 –VOL. 12, NO. 7
24.
25.
HEMATOCRIT, HYPERVISCOSITY, AND BLOOD PRESSURE
Cannon RO III, Bonow RO, Bacharach SL, Green MW, Rosing DR, Leon MB, Watson RM, Epstein SE: Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation 1985;71:218 –226. Hintze TH, Vatner SF: Reactive dilation of large coronary arteries in conscious dogs. Circ Res 1984;54:50 –57.
743
26.
Feldman RL, Marx JD, Pepine CJ, Conti CR: Analysis of coronary responses to various doses of intracoronary nitroglycerin. Circulation 1982;66:321–327.
27.
Athens JW: Polycytemia Vera, in Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN (eds): Wintrobe’s Clinical Hematology, Ninth Ed. Lea and Febiger; Philadelphia, 1993, pp 1999 –2017.