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Physical factors affecting human blood viscosity
PHYSICAL
MARTIN
S.
LITWIN,
FACTORS BLOOD M.D.*
PREVIOUS EXPERIMENTS PERFORMED in this laboratory have demonstrated a close direct relationship in the normal human between hematocrit and whole blood viscosity. Correlation of the two has been found to be 78% [2]. Other physical factors are also important determinants of blood viscosity. These include blood flow rate, physical and biochemical characteristics of the plasma and of the formed elements, internal size and surface characteristics of the blood vessel, and temperature of the blood. In determining the viscosity of any fluid-flow system such as blood in which physical and biochemical characteristics of the system may change from moment to moment, the length of time the fluid has been allowed to remain at rest in vitro prior to viscosity determination may also be of importance. It was the purpose of these experiments to illustrate the relationship between hematocrit and whole blood viscosity in the normal human and to determine the influence on normal human whole blood viscosity of temFrom the Shock and Trauma Laboratory, Department of Surgery, Tulane University School of Medicine. Su ported by U.S. Army Medical Research and Deve Popment Command, Contract No. DADA17-67c-7049. *Public Health Service Research Career Program Awardee l-K3-HE-38, 604-01 from the National Heart Institute. Submitted for publication March 30, 1970.
AFFECTING VISCOSITY AND
KENNETH
HUMAN
CHAPMAN,
B.S.
perature of the blood and length of time on standing in vitro.
METHODS
AND
MATERIALS
Venous blood samples from normal healthy adults were studied. Excluded were those individuals with a &tory of either minor or major illness during the preceding 3 months, those with a possible history of chronic disease and menstruating women. Highest hematocrit noted was 53% and the lowest 36%. Using these high and low values and an intermediate value of 4-4%, which was also noted, standard viscosity curves were prepared from these data. In order to determine the effect of temperature on whole blood viscosity blood samples were taken hourly by venipuncture from five normal subjects. Whole blood viscosity determinations were done immediately at 25, 30, 35, and 37.5”C. In order to determine the effect of in vitro “standing” time on whole blood viscosity, venous blood samples were taken from four other subjects and allowed to sit at room temperature. Whole blood viscosity of each sample was determined immediately after venipuncture, at hourly intervals for 12 hours and again 24 hours after the sample was taken. All blood samples were taken by freeflow433
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
9,
ing venipuncture through large-bore needles into plastic syringes lubricated with the minimal amount of heparin necessary to prevent clotting. Each experiment was verified in triplicate, and all viscosity determinations were performed in a Wells-Brookfield synchrolectric viscometer. Temperature was maintained constant at 37S”C. except in those experiments in which the effect of temperature variation was studied.
The relationship of hematocrit and normal human whole blood viscosity is graphically illustrated (Fig. 1). At all shear rates studied and an hematocrit of 53%, whole blood viscosity was approximately double the whole blood viscosity when hematocrit was only 36%. At an hematocrit of 44% the viscosity curve fell approximately half-way between the upper and lower extremes. The relationship between temperature and normal human whole blood viscosity at a constant hematocrit is illustrated by the typical experiment shown (Fig. 2). In all experiments viscosity increased with decreasing temperature. Viscosity increase was
DISCUSSION In the present experiments the relationship between hematocrit and whole blood viscosity in the normal human has been illustrated. Utilizing a Wells-Brookfield synchrolectric viscometer, viscosity of whole blood with an hematocrit of 53% was found to be essentially twice that of whole blood with an hematocrit of 36%. The relationship between hematocrit and whole blood viscosity was not found to be a linear one; thus, this experiment il-
HEMATOCRIT . 53 -1. a 44 %
‘\
5.8
1970
definite and significant at all shear rates, but changes were particularly exaggerated at the lower shear rates. When whole blood was taken from normal individuals and viscosity determinations done at hourly intervals, significant fluctuations in viscosity were noted (Fig. 3). These changes appeared to be minor at the higher shear rates; however, they were exaggerated and very significant (p < 661) at the lower shear rates. Throughout all experiments there appeared to be an alternation between increase and marked decrease in whole blood viscosity which occurred in approximately 3-hourly cycles.
RESULTS
0
SEPTEMBER
11.5
46
23
Shear
II,
Rote
I,”
/set-7
Fig. 1. Relation of whole blood viscosity to hematocrit in the normal human. At all shear rates studied the viscosity of normal human blood with an hematocrit of 36% was approximately one-half the viscosity of normal human blood with an hematocrit of 53%. When hematocrit was 44% the viscosity curve fell approximately half way between the upper and lower curves. 434
LITWIN
AND
CHAPMAN:
HUMAN
BLOOD
VISCOSITY
20 .
TEM.FE;;TFRE . A
\
Fig. 2. Effect of temperature In all experiments, including noted at lower temperatures.
on viscosity of whole blood from the normal human (hematocrit 45% ). the one illustrated, viscosity at 37.5”C. was considerably less than
1 46 0 ::z
Fig. 3. Normal human whole blood viscosity as a function of length of time blood has remained at rest in vitro (hematocrit 46q0 ) . Viscosity curves at varying shear rates in this experiment are represented by lines between the corresponding symbols. Symbols to the right on the diagram represent viscosity at 24 hours after the blood sample was obtained. Marked fluctuations in whole blood viscosity at approximately 3-hour intervals were noted in all experiments. These viscosity alterations were in evidence at all shear rates and most exaggerated
at the lower
shears.
30-c
lustrates that hematocrit is not the only determinant of whole blood viscosity changes, even in the normal human. Rand et al. (4) studied the effect of temperature on human blood samples in which hematocrits had been adjusted to 0, 20, 40, 60, and 80% by addition or removal of plasma. They found that between 37 and 27°C. a linear rise in viscosity occurred at each shear rate, regardless of hematocrit. Below 27°C however, viscosity increased out of proportion to the degree of cooling with the greater elevations seen when hematocrit was high and shear rate low. In the present experiments the temperature at which blood viscosity was determined was also found to be an extremely important determinant of viscosity of unaltered fresh human whole blood samples. Viscosity at 25°C. was markedly greater than viscosity of the same blood sample when measured at 37S”C., and the changes observed between 30” and 25°C. were greater than the changes which occurred between 35” and 30°C. Whether these effects were purely physical ones or the result of induced changes or reactions between cells and plasma or a combination of the two has yet to be determined. Mundth et al. (3) and Knize et al. (1) 435
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
have demonstrated the usefulness of certain antisludging agents in the treatment of freezing and frostbite. The decrease in tissue blood flow observed in these conditions may be partially the result of the marked increase in blood viscosity which occurs at lower temperatures noted in the present experiments. These effects may be overcome either by warming or by therapeutic hemodilution. Infusions of antisludging agents decrease blood viscosity not only by causing a dilutional decrease in hematocrit and plasma proteins but also they probably partially deactivate certain clotting elements, the latter by either coating or by chemical complexing. In order that a blood viscosity determination accurately reflect the characteristics of blood in vivo, it is important that the temperature of the peripheral vascular bed be known. During shock or any other low flow state, capillary or arteriolar beds constrict and become dramatically cooler than the central circulation. Until such a circulatory bed has rewarmed, a blood viscosity determination done at 375°C. will give little indication of the viscous characteristics of the same blood less centrally located and colder. In the past little emphasis has been placed on the relation of the length of time blood has been allowed to remain in vitro prior to viscosity determinations. The experiments shown in Fig. 3 illustrate that there are systems at work in vitro which can lead to false determinations when the whole blood viscosity is not measured soon after the blood sample has been removed. Marked in vitro fluctuations were noted at approximately
436
9,
SEPTEMBER
1970
3-hour intervals. This may be a manifestation of intermittent fibrinolytic activity. In any case this research emphasizes that when whoIe blood viscosity is to be done, the determination should be carried out as soon after venipuncture as is possible.
SUMMARY Human blood viscosity was measured under varying conditions to determine the influence of certain physical factors on this parameter. Normal human blood viscosity at an hematocrit of 36% was only one-half the blood viscosity noted when hematocrit was 53%. Whole blood viscosity determined at 37.5”C. was markedly less than whole blood viscosity of the same blood when determined at 25°C. Marked fluctuations in viscosity were noted when blood was allowed to remain in vitro for long peri0ds of time prior to viscosity determinations.
REFERENCES Knize, D. M., WeatherIy-White, R. C. A., and Paton, B. C.: Use of antisludging agents in experimental cold injuries. Surg. Gynec. Obstet. 129:1019, 1969. Litwin, M. S., Chapman, K., and Stohar, J. B.: Blood viscosity in the normal human. Surgery 67:342, 1970. Mundth, L. D., Long, D. M., and Brown, R. B.: Treatment of experimental frostbite with low molecular weight dextran. J. TTUU~U 4:246, 1964. Band, P. W., Lacombe, E., Hunt, H. E., and Austin, W. H.: Viscosity of normal human blood under normothermic and hypothermic conditions, J. Appl. Physiol. 19:117, 1964.
MARTIN
S.
LITWIN,
FACTORS BLOOD M.D.*
PREVIOUS EXPERIMENTS PERFORMED in this laboratory have demonstrated a close direct relationship in the normal human between hematocrit and whole blood viscosity. Correlation of the two has been found to be 78% [2]. Other physical factors are also important determinants of blood viscosity. These include blood flow rate, physical and biochemical characteristics of the plasma and of the formed elements, internal size and surface characteristics of the blood vessel, and temperature of the blood. In determining the viscosity of any fluid-flow system such as blood in which physical and biochemical characteristics of the system may change from moment to moment, the length of time the fluid has been allowed to remain at rest in vitro prior to viscosity determination may also be of importance. It was the purpose of these experiments to illustrate the relationship between hematocrit and whole blood viscosity in the normal human and to determine the influence on normal human whole blood viscosity of temFrom the Shock and Trauma Laboratory, Department of Surgery, Tulane University School of Medicine. Su ported by U.S. Army Medical Research and Deve Popment Command, Contract No. DADA17-67c-7049. *Public Health Service Research Career Program Awardee l-K3-HE-38, 604-01 from the National Heart Institute. Submitted for publication March 30, 1970.
AFFECTING VISCOSITY AND
KENNETH
HUMAN
CHAPMAN,
B.S.
perature of the blood and length of time on standing in vitro.
METHODS
AND
MATERIALS
Venous blood samples from normal healthy adults were studied. Excluded were those individuals with a &tory of either minor or major illness during the preceding 3 months, those with a possible history of chronic disease and menstruating women. Highest hematocrit noted was 53% and the lowest 36%. Using these high and low values and an intermediate value of 4-4%, which was also noted, standard viscosity curves were prepared from these data. In order to determine the effect of temperature on whole blood viscosity blood samples were taken hourly by venipuncture from five normal subjects. Whole blood viscosity determinations were done immediately at 25, 30, 35, and 37.5”C. In order to determine the effect of in vitro “standing” time on whole blood viscosity, venous blood samples were taken from four other subjects and allowed to sit at room temperature. Whole blood viscosity of each sample was determined immediately after venipuncture, at hourly intervals for 12 hours and again 24 hours after the sample was taken. All blood samples were taken by freeflow433
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
9,
ing venipuncture through large-bore needles into plastic syringes lubricated with the minimal amount of heparin necessary to prevent clotting. Each experiment was verified in triplicate, and all viscosity determinations were performed in a Wells-Brookfield synchrolectric viscometer. Temperature was maintained constant at 37S”C. except in those experiments in which the effect of temperature variation was studied.
The relationship of hematocrit and normal human whole blood viscosity is graphically illustrated (Fig. 1). At all shear rates studied and an hematocrit of 53%, whole blood viscosity was approximately double the whole blood viscosity when hematocrit was only 36%. At an hematocrit of 44% the viscosity curve fell approximately half-way between the upper and lower extremes. The relationship between temperature and normal human whole blood viscosity at a constant hematocrit is illustrated by the typical experiment shown (Fig. 2). In all experiments viscosity increased with decreasing temperature. Viscosity increase was
DISCUSSION In the present experiments the relationship between hematocrit and whole blood viscosity in the normal human has been illustrated. Utilizing a Wells-Brookfield synchrolectric viscometer, viscosity of whole blood with an hematocrit of 53% was found to be essentially twice that of whole blood with an hematocrit of 36%. The relationship between hematocrit and whole blood viscosity was not found to be a linear one; thus, this experiment il-
HEMATOCRIT . 53 -1. a 44 %
‘\
5.8
1970
definite and significant at all shear rates, but changes were particularly exaggerated at the lower shear rates. When whole blood was taken from normal individuals and viscosity determinations done at hourly intervals, significant fluctuations in viscosity were noted (Fig. 3). These changes appeared to be minor at the higher shear rates; however, they were exaggerated and very significant (p < 661) at the lower shear rates. Throughout all experiments there appeared to be an alternation between increase and marked decrease in whole blood viscosity which occurred in approximately 3-hourly cycles.
RESULTS
0
SEPTEMBER
11.5
46
23
Shear
II,
Rote
I,”
/set-7
Fig. 1. Relation of whole blood viscosity to hematocrit in the normal human. At all shear rates studied the viscosity of normal human blood with an hematocrit of 36% was approximately one-half the viscosity of normal human blood with an hematocrit of 53%. When hematocrit was 44% the viscosity curve fell approximately half way between the upper and lower curves. 434
LITWIN
AND
CHAPMAN:
HUMAN
BLOOD
VISCOSITY
20 .
TEM.FE;;TFRE . A
\
Fig. 2. Effect of temperature In all experiments, including noted at lower temperatures.
on viscosity of whole blood from the normal human (hematocrit 45% ). the one illustrated, viscosity at 37.5”C. was considerably less than
1 46 0 ::z
Fig. 3. Normal human whole blood viscosity as a function of length of time blood has remained at rest in vitro (hematocrit 46q0 ) . Viscosity curves at varying shear rates in this experiment are represented by lines between the corresponding symbols. Symbols to the right on the diagram represent viscosity at 24 hours after the blood sample was obtained. Marked fluctuations in whole blood viscosity at approximately 3-hour intervals were noted in all experiments. These viscosity alterations were in evidence at all shear rates and most exaggerated
at the lower
shears.
30-c
lustrates that hematocrit is not the only determinant of whole blood viscosity changes, even in the normal human. Rand et al. (4) studied the effect of temperature on human blood samples in which hematocrits had been adjusted to 0, 20, 40, 60, and 80% by addition or removal of plasma. They found that between 37 and 27°C. a linear rise in viscosity occurred at each shear rate, regardless of hematocrit. Below 27°C however, viscosity increased out of proportion to the degree of cooling with the greater elevations seen when hematocrit was high and shear rate low. In the present experiments the temperature at which blood viscosity was determined was also found to be an extremely important determinant of viscosity of unaltered fresh human whole blood samples. Viscosity at 25°C. was markedly greater than viscosity of the same blood sample when measured at 37S”C., and the changes observed between 30” and 25°C. were greater than the changes which occurred between 35” and 30°C. Whether these effects were purely physical ones or the result of induced changes or reactions between cells and plasma or a combination of the two has yet to be determined. Mundth et al. (3) and Knize et al. (1) 435
JOURNAL
OF
SURGICAL
RESEARCH
VOL.
10
NO.
have demonstrated the usefulness of certain antisludging agents in the treatment of freezing and frostbite. The decrease in tissue blood flow observed in these conditions may be partially the result of the marked increase in blood viscosity which occurs at lower temperatures noted in the present experiments. These effects may be overcome either by warming or by therapeutic hemodilution. Infusions of antisludging agents decrease blood viscosity not only by causing a dilutional decrease in hematocrit and plasma proteins but also they probably partially deactivate certain clotting elements, the latter by either coating or by chemical complexing. In order that a blood viscosity determination accurately reflect the characteristics of blood in vivo, it is important that the temperature of the peripheral vascular bed be known. During shock or any other low flow state, capillary or arteriolar beds constrict and become dramatically cooler than the central circulation. Until such a circulatory bed has rewarmed, a blood viscosity determination done at 375°C. will give little indication of the viscous characteristics of the same blood less centrally located and colder. In the past little emphasis has been placed on the relation of the length of time blood has been allowed to remain in vitro prior to viscosity determinations. The experiments shown in Fig. 3 illustrate that there are systems at work in vitro which can lead to false determinations when the whole blood viscosity is not measured soon after the blood sample has been removed. Marked in vitro fluctuations were noted at approximately
436
9,
SEPTEMBER
1970
3-hour intervals. This may be a manifestation of intermittent fibrinolytic activity. In any case this research emphasizes that when whoIe blood viscosity is to be done, the determination should be carried out as soon after venipuncture as is possible.
SUMMARY Human blood viscosity was measured under varying conditions to determine the influence of certain physical factors on this parameter. Normal human blood viscosity at an hematocrit of 36% was only one-half the blood viscosity noted when hematocrit was 53%. Whole blood viscosity determined at 37.5”C. was markedly less than whole blood viscosity of the same blood when determined at 25°C. Marked fluctuations in viscosity were noted when blood was allowed to remain in vitro for long peri0ds of time prior to viscosity determinations.
REFERENCES Knize, D. M., WeatherIy-White, R. C. A., and Paton, B. C.: Use of antisludging agents in experimental cold injuries. Surg. Gynec. Obstet. 129:1019, 1969. Litwin, M. S., Chapman, K., and Stohar, J. B.: Blood viscosity in the normal human. Surgery 67:342, 1970. Mundth, L. D., Long, D. M., and Brown, R. B.: Treatment of experimental frostbite with low molecular weight dextran. J. TTUU~U 4:246, 1964. Band, P. W., Lacombe, E., Hunt, H. E., and Austin, W. H.: Viscosity of normal human blood under normothermic and hypothermic conditions, J. Appl. Physiol. 19:117, 1964.