VISCOSITY STUDIES OF BLOOD, PLASMA, AND PLASMA SUBSTITUTES

VISCOSITY STUDIES OF BLOOD, PLASMA, AND PLASMA SUBSTITUTES

VISCOSITY STUDIES OF BLOOD, PLASMA, A N D PLASMA SUBSTITUTES Keith Reemtsma, M.D. (by invitation), and Oscar Creech, Jr., M.D., New Orleans, La. ...

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VISCOSITY STUDIES OF BLOOD, PLASMA, A N D PLASMA SUBSTITUTES Keith Reemtsma,

M.D.

(by invitation),

and

Oscar Creech, Jr., M.D., New Orleans, La.

V

physiologic responses in extracorporeal circulation have been studied extensively, but scant attention has been directed toward physical changes in perfusing media. Studies of viscosity have assumed increased importance with the widespread use of hypothermia and the introduction of diluents to extracorporeal circuits. The present report describes the use of an ultrasonic viscometer in studies on viscosity of plasma, various dextran solutions, and blood with different hematocrit levels. ARIOUS

VISCOMETER

The ultrasonic viscometer* comprises a probe, an electronic analog computer, and a connecting cable.12 Viscosity is measured by immersing a thin alloy steel blade on the end of the probe in the fluid under study. The blade is excited by an electrical pulse from the computer. This produces ultrasonic shear waves in the material surrounding the blade, causing layers of the material to slip back and forth. The electronic computer converts the energy required to produce the sliding motion into viscosity measurements. Viscosity is recorded automatically and continuously. Response time is less than one second, and peak displacement amplitude is less than 0.5 micron. MATERIAL AND METHODS

Fresh blood was obtained from donor dogs anesthetized with pentobarbital sodium administered intravenously in a dose of 30 mg. per kilogram. Heparin was added to the freshly drawn blood in a dose of 20 mg. per 500 ml. For studies on blood with different hematocrits, the blood was allowed to settle for 24 hours. Plasma and cells were pipetted into separate containers and reconstituted at various corpuscular concentrations. After viscosity studies were La.

From the Department of Surgery, Tulane University School of Medicine, New Orleans,

Supported in part by grants from the Louisiana Heart Association and the National Institutes of Health, H-5638. Read at the Forty-second Annual Meeting of The American Association for Thoracic Surgrery a t St. Louis, Mo., April 16-18, 1962. •Ultra-Viscoson, Bendix Aviation Corporation, Cincinnati 8, Ohio. 674

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November, 1962

675

performed, actual hematocrits were determined by centrifuging blood samples in hematocrit tubes. Studies were also performed on dextran solutions of various concentrations and differing molecular weights, ranging from 15,000 to 300,000.* For studies at 37° C , a circulating water bath with temperature control was used. For viscosity determinations at lower temperatures, largebore test tubes containing the fluid under study were immersed in an ice water solution, the temperature of which was checked with a standard mercury thermometer. RESULTS

A. Studies on Apparent Viscosity of Blood With Different Hematocrit Levels.—At hematocrit levels between 10 and 40 per cent, there was only slight increase in viscosity with increasing hematocrits. However, above 40 per cent, the viscosity increased more sharply with increasing hematocrit levels, and this change was even more marked at levels above 60 per cent (Fig. 1).

5

8 >

O

10

2D

30 40 50 60 HEMATOCRIT

70

60

90

Fig. 1.—Diagram of viscosity determinations of blood of various hematocrit levels. All studies were performed at 37° C. Viscosity units: centipoises times grams per cubic centimeter.

In a series of studies at lower temperatures, the increase in viscosity as temperature was lowered was more marked in blood samples with higher hematocrits (Fig. 2, Table I ) . TABLE TEMPERATURE (DEGREES C.)

5° 10° 15° 20° 25° 30° 35° 40°

I HEMATOCRIT

89% | 72% | 67% | 5 8 % | 50% | 42% | 32% | 26% | 15% 20.0 4.2 3.2 3.0 16.4 14.0 10.5 6.5 5.6 5.5 3.2 2.4 15.0 12.2 9.6 7.5 4.2 2.1 11.8 10.0 8.4 6.0 4.8 3.8 2.8 2.0 2.0 4.4 3.0 2.5 1.9 9.8 1.8 8.8 6.4 4.5 7.8 5.8 3.5 3.3 2.5 2.0 1.8 8.8 1.8 7.2 6.6 4.8 3.0 3.0 2.1 1.8 1.7 1.7 6.6 5.8 3.7 2.6 2.6 2.0 1.8 1.7 1.7 5.2 3.2 2.2 2.0 1.8 1.7 1.5 5.4 1.5

7% 2.8 2.0 1.8 1.7 1.6 1.6 1.5 1.4

•Supplied by Pharmacia Laboratories, New York, and Baxter Laboratories, Inc., Morton Grove, Illinois.

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J. Thoracic and Cardiovas. Surg.

B. Studies on Viscosity of Dextran Solutions of Various Molecular Weights. —Dextran solution with a molecular weight of 15,000 to 20,000 showed a viscosity pattern similar to that of plasma. Studies were also performed on dextran solutions with molecular weights ranging from 60,000 to 300,000. Viscosity increased with molecular weight, and the increase in viscosity was more marked at lower temperature levels (Table II, Fig. 3).

LO

L"3 HO

£5

35

30

TEM.PERATU.RE: C°

40

Fig. 2.—Diagram of viscosity determinations of blood of various hematocrit levels at temperatures ranging from 5° to 40° C. There is marked increase in viscosity of blood with high hematocrit levels at low temperatures. Viscosity units: centipoises times grams per cubic centimeter. 20

ia 1G

gio

200,000-300,000

>

100,000-200,000

6Q0O0-9QO00

15,0,00-20,000 '-PLASMA

lO

15

SO

25

30

35

TEM.PEEA.TU.RE; C °

40

Fig. 3.—Diagram of viscosity determinations of dextran of various molecular weights at temperatures ranging from 5° to 40° C. In solutions with high molecular weight viscosity increases markedly at low temperatures. Viscosity units: centipoises times grams per cubic • centimeter. Dextran studies performed with 10 per cent solutions.

Vol. 44, No. 5 November, 1962

VISCOSITY

STUDIES

TABLE

TEMPERATURE (DEGREES C.)

DOG PLASMA

5° 10° 15° 20° 25° 30° 35° 40°

2.6 1.9 1.7 1.6 1.5 1.4 1.3 1.2

677

II

DEXTRAN (M.W. DEXTRAN (M.W. DEXTRAN (M.W. DEXTRAN (M.W. 15,000-20,000) 60,000-90,000) 100,000-200,000) 200,000-300,000) 3.7 2.4 2.2 2.0 1.9 1.8 1.6 1.5

11.8 8.0 7.3 6.6 6.3 5.7 5.0 4.5

17.0 12.0 11.6 9.8 9.2 8.2 7.4 6.8

19.4 15.0 13.0 12.0 11.2 10.0 9.0 8.2

The 6 per cent solution of low molecular weight dextran, which has an average molecular weight of 38,600, was more viscous than plasma at all temperature levels, and viscosity increased more markedly at lower temperature levels (Table I I I , Fig. 4).

L2 hi0

u in

>6

to UMWD

G ^ HMWD r x 6<7o LMWD —o PLASMA

10

t5 SO £5 3 0 3 5 AO T E M P E R A T U R E C° Fig. 4.—Diagram of viscosity determinations of different dextran solutions compared with plasma. The 6 per cent low molecular weight dextran w a s more viscous t h a n plasma a t all temperatures, a n d viscosity increased more markedly a t low temperatures. Viscosity u n i t s : centipoises times g r a m s per cubic centimeter. TABLE TEMPERATURE (DEGREES c.)

5° 10° 15° 20° 25° 30° 35° 40°

III

6% LOW

1 5 % LOW

PLASMA

MOLECULAR W E I G H T DEXTRAN

6 % HIGH MOLECULAR W E I G H T DEXTRAN

MOLECULAR W E I G H T DEXTRAN

3.0 2.2 2.0 1.8 1.8 1.6 1.4 1.4

7.8 5.5 5.2 4.5 4.2 4.0 3.4 3.4

9.4 7.6 6.6 6.2 5.6 5.2 4.4 4.2

16.5 13.0 11.2 10.0 9.2 8.0 7.0 6.8

DISCUSSION

In the early clinical experience with extracorporeal circulation, blood was used as the perfusing fluid. Subsequently dextran solutions of low molecular weight have been added to the oxygenator, 10 and in some instances crystalloid

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solutions have been used to fill the extracorporeal circuit." Considerable physiologic data on such perfusions have been accumulated, but there is scant quantitative information on viscosity of various perfusing solutions. The use of varying degrees of hypothermia further complicates analysis of physical changes involved. The first studies relating viscosity to flow were reported in 1841 by Poiseuille, 11 who defined the law of flow of liquids through rigid tubes. In 1906, Denning and Watson 4 reported a series of viscosity studies on plasma and blood. They observed that the effect of temperature on viscosity was less for plasma than for blood and less for blood with low hematocrit levels than blood with high hematocrit levels. They also reported that the apparent viscosity of blood was dependent upon the diameter of the tube, and, subsequently, Hess 8 observed that blood viscosity was related to velocity of flow. I n 1918, Trevan 14 studied the relation of corpuscular volume to viscosity and observed a slight increase in viscosity with an increasing hematocrit up to 40 per cent. The slope became somewhat steeper above 40 per cent, and above 60 per cent there was a sharp increase in viscosity with increased corpuscular concentration. In more recent studies on blood viscosity, attention has been directed toward anomalous properties of blood viscosity and toward investigation of "shear rate" and "shear stress." Various types of viscometers have been used in these studies. 1 ' '•3'15 In the present study, an ultrasonic viscometer was used which consists of a probe with a thin alloy blade and an electronic computer. Shearing is produced in the material under study by an electrical pulse from the computer. The computer converts the energy required to produce the shearing into viscosity measurements. This viscometer has been used in other laboratories in studies of blood clotting. 9 ' 16 The purpose of the present study was to evaluate aspects of viscosity which are pertinent to current work in extracorporeal circulation and hypothermia. The relationship of corpuscular concentration to viscosity observed in our studies was similar to that observed by Trevan in 1918. Of particular interest, however, are the marked changes in viscosity seen with profound hypothermia, particularly in blood with high hematocrit levels. These findings assume added importance now that certain individuals with high hematocrit levels, especially patients with tetralogy of Fallot, are occasionally subjected to profound hypothermia for repair of cardiac defects. Recent developments in extracorporeal circulation have included the use of "diluents" in the pump-oxygenator system. Low molecular weight dextran has been widely used clinically 10 and experimentally, 5 ' G ' 7> 13 and the results have been favorably reported. The present studies suggest that low molecular weight dextran is not a diluent of plasma in the usual sense, since in both 6 and 10 per cent solutions, as usually supplied, it is more viscous than plasma itself. However, low molecular weight dextran serves to reduce the hemato-

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crit, and, by this mechanism, may reduce the apparent viscosity of whole blood. The reported beneficial effects of low molecular weight dextran during extracorporeal circulation may be related to factors other than changes in viscosity. SUMMARY

1. Viscosity studies of plasma, various dextran solutions, and blood with different hematoerit levels were performed with an ultrasonic viscometer. 2. At 37° C , there was only slight increase in viscosity with increasing hematocrits from 10 to 40 per cent. Above 40 per cent, viscosity increased more sharply with increasing hematoerit levels, and this change was even more marked at levels above 60 per cent. 3. As temperature was lowered, viscosity increased more steeply in blood with high hematoerit levels. 4. In solutions of dextran of different molecular weights, viscosity increased with molecular weight. As temperature was lowered, viscosity increased more sharply in the higher molecular weight solutions. 5. Low molecular weight dextran in 6 per cent solution was more viscous than plasma; however, such a solution may lower the apparent viscosity of whole blood by lowering the hematoerit level. 6. Viscosity may be of particular clinical importance under conditions of high hematoerit levels and profound hypothermia. The authors wish to express appreciation to Dr. James E. P a y n e , Jr., and Dr. Don W. Turner, and to Mr. Tim N. Howell and Mr. Charles A. Thoman, Jr., who performed numerous viscosity studies during summer student research fellowships in The Department of Surgery. We wish to t h a n k Miss Valerie E r n s t and Miss I v y Fey for technical assistance and Miss Vera Morel for illustrative material. REFERENCES

1. Bavliss, L. E.: The Axial Drift of the Red Cells When Blood Flows in a Narrow Tube, J. Physiol. 149: 593, 1959. 2. Brundage, J. T.: Blood and Plasma Viscosity Determined by the Method of Concentric Cylinders, Am. J. Physiol. 110: 659, 1934. 3. Copley, A. L., Krchma, L. C , and Whitney, M. E.: Humoral Eheology: Viscosity Studies and Anomalous Flow Properties of Human Blood Systems With Heparin and Other Anticoagulants, J. Gen. Physiol. 26: 49, 1942. 4. Denning, A. D., and Watson, J. H.: The Viscosity of Blood, Proc. Roy. Soc. Series B 78: 328, 1906. 5. Finsterbusch, W., Long, D. M., Sellers, R. D., Amplatz, K., and Lillehei, C. W.: Renal Arteriography During Extracorporeal Circulation in Dogs W i t h a Preliminary Report Upon t h e Effects of Low Molecular Weight Dextran, J. THORACIC SURG. 41: 252, 1961. 6. Gelin, L. E., and Lofstrom, B.: A Preliminary Study on Peripheral Circulation During Deep Hypothermia, Acta chir. scandinav. 108: 402, 1955. 7. Gelin, L. E.: Studies in Anemia of Injury, Acta chir. scandinav. Suppl. 210, 1956. 8. Hess, W. R.: Der strbmungswiderstand des blutes gegeniiber klernen druckwerten, Arch. Physiol. Leipzig, p. 197, 1912. 9. Holliday, R. W.: The Measurement of Viscosities of Clotting Specimens of Blood W i t h the Ultra-Viscoson, Thesis, Doctor of Medical Science, Columbia University, 1957. 10. Long, D. M., Jr., Sanchez, L., Varco, R. L., and Lillehei, C. W.: The Use of Low Molecular Weight Dextran in Serum Albumin as Plasma Expanders in Extracorporeal Circulation, Surgery 50: 12, 1961.

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11. Poiseuille, M.: Eecherches experimentales sur le mouvement des liquids dans les tubes de tr&3 petits diametres, Des Seances de L'Academie des Sciences 1 1 : 961-967; 1041-1048, 1841. 12. Eoth, W., and Eich, S. E.: A New Method for Continuous Viscosity Measurements: General Theory of the Ultraviscoson, J . Appl. Physics 24: 940, 1953. 13. Thorsen, G., and Hint, H.: Aggregation, Sedimentation, and I n t r a vascular Sludging of Erythrocytes, Acta chir. scandinav. Suppl. 154, 1950. 14. Trevan, J . W.: The Viscosity of Blood, Biochem. J . 12: 60, 1918. 15. Wells, E. E., Jr., and Merrill, E. W.: The Variability of Blood Viscosity, Am. J. Med. 3 1 : 505, 1961. 16. Yesner, E., Hurwitz, A., Eich, S. E., Eoth, W., and Gordon, M. E.: Preliminary Observations on Blood Coagulation Utilizing Ultrasonics for Continuous Measurement of Viscosity, Yale J. Biol. Med. 24: 231, 1951. 17. Zuhdi, N., McCollough, B., Carey, J., Krieger, C , and Greer, A.: Hypothermic Perfusion for Open-Heart Surgical Procedures, J . I n t e r n a t . Coll. Surgeons 35: 319, 1961. (For Discussion, see page 695)