Effect of blood viscosity on pulmonary vascular resistance

Effect of Blood Viscosity on Pulmonary Vascular Resistance By KENNETHR. T. TYSON, NESTORSCIARROTTA, H. ROBERTSFENDER,AND LINEA A. MCNEEL

I

N THE TREATMENT of congenital cyanotic heart disease, the effectiveness of palliative shunts between the systemic arterial or systemic venous circulation and the pulmonary arterial circulation is dependent in no small part upon resistance to pulmonary blood flow. Factors that increase pulmonary vascular resistance tend to decrease the volume flow to the lungs by way of these shunts, and hence, to decrease their effectiveness. It has long been known that increased blood viscosity increases systemic vascular resistance and, secondarily, decreases total cardiac output in the intact circu1ation.r Similar changes of increased pulmonary vascular resistance have been seen when blood viscosity is increased; but since increased pulmonary vascular resistance occurs in the face of diminished cardiac output for whatever cause, it is not known whether increased blood viscosity is a primary factor in increasing resistance in the pulmonary circulation or if the increased pulmonary vascular resistance observed is a consequence only of diminished cardiac output. Since the functional effectiveness of systemic arterial or venous-pulmonary artery shunts is dependent primarily upon pulmonary vascular resistance, it seems important to determine what effect changes in blood viscosity have on pulmonary vascular resistance independent of changes in cardiac output. MATERIALS AND METHODS Twelve adult mongrel dogs free of heart worms were used in this series. Each was lightly anesthetized with intravenous sodium pentobarbital. Controlled positive pressure breathing was carried out by way of an orotracheal tube connected to a volume ventilator. Anesthesia was maintained by way of an inhaled gas mixture of 80°C nitrous oxide and 20% oxygen. In addition, intermittent doses of intravenous succinylcholine were used. Through a median stemotomy the heart and great vessels were exposed. Pressures were measured in the aorta. pulmonary artery, left atrium, and right atrium by way of indwelling catheters connected to pressure transducers. Cardiac output was measured by placement of an electromagnetic flow probe (Electromagnetic Probe Co., Winston-Salem, N. C. ) around the ascending aorta and connection of the probe to a square-wave electromagnetic flow meter (Carolina Medical

From the Pediatric Surgical Service, Department of Surgery, University of Texas Medical Branch at Galveston, Tex. Presented before the American Pediatric Suqical Association. Hamilton, Bermuda, April 22-24,197l. Supported by US:PHS Grant HE 11429-02. KENNETH R. T. TYSON. M.D.: A.&stunt Professor Departments of Sur,ocry and Pediatrics, Chief Pediatric Surgical Seroice, University of Texas Medical Branch of Galveston, Ter. NESTOR SCIARROTTA,M.D.: Buenos Aires, Argentitra; form&y Research Associate, Pediatric Surgical Service, Department of Surgery, University of Texas Medical Branch at Galveston, Tex. H. ROBERTSFENDER, B.S.: nledical Student. University of Texas Medical Branch at Galveston, Tex. LINEA A. ~~CNEEL, B.S.: Senior Research Technician. Sur@cal Rescarrh Laboratories, University of Texas Medical Branch at Galveston, Tex.

JOURNALOF PEDIATRICSURGERY,VOL. 6, No. 5 ( OCTORER). 1971

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Electronics, Winston-Salem, N.C.). Hematocrit, blood viscosity, and arterial PO,, pCO,, and pH values were monitored. To an incision in the anterior wall of the distal ascending aorta was sewn a I2 mm arterial prosthesis. The azygous vein was ligated, and a large catheter was introduced into the superior vena cava by way of the left innominate vein. The animal was given intravenous heparin. and the aortic and superior vena cava tubes were connected to the Starling heart-lung apparatus consisting of a windkessel, a variable resistor, and a reservoir with a heat exchanger to keep the blood temperature at 99’F. The supracardiac vagi were sectioned or crushed, and the system was filled with isologous blood. The preparation was completed by occlusion of the ascending aorta distal to the arterial prosthesis, occlusion of the inferior vena cava, and tightening of the ligature around the venous return tube in the superior vena cava. To avoid the deleterious effects of glucose and neurohormone depletion in the standard heart-lung preparation, a dilute solution of isoproterenol in 10% glucose was dripped slowly into the reservoir. In addition, carbon dioxide was added to the inspired gases sufficient to keep the arterial pC0, and pH at normal levels. In experiments preceding this series, attempts had been made to use homologous packed red blood cells and plasma to vary the hematocrit and the blood viscosity. These studies were discarded because of inconsistent and widely variable changes in pulmonary vascular resistance, probably because of minor blood incompatibilities. Instead, each dog studied in this series was bled 500-600 cc of whole blood 5-7 days prior to this study period. On the day of study, heparin was added to the blood collected, the blood pH was returned to normal levels by the addition of Tris buffer, and the sodium citrate was neutralized by addition of calcium chloride. The plasma and red blood cells were then separated by centrifugation into separate bags. After a suitable period of stabilization of the preparation, alternate dogs had exchange of the reservoir blood for autologous plasma or packed red blood cells, followed by exchange of the reservoir blood for the remaining packed red blood cells or plasma. Cardiac output was maintained constant through all of the study periods by minor variations in arterial resistance of the preparation and height of the venous reservoir. RESULTS

Using the Brookfield one-half LVT microviscometer,2 very consistent relationships between hematocrit and blood viscosity could be obtained at shear rates of from 46 to 2.4 inverse seconds. As is characteristic of any thixotropic fluid, most marked changes in viscosity were seen at the lower shear rates (see Fig. 1). The range of shear rates utilized in this study for determination of viscosity was chosen because pulmonary arteriolar and capillary blood flow has been estimated to ocur at shear rates from 20 to 5 inverse seconds.3 Because of the very high degree of correlation between hematocrit and blood viscosity in each animal studied, we have chosen to refer subsequently to levels of hematocrit rather than blood viscosity at an arbitrary shear rate. Cardiac output ranged between 500 and 980 cc/min, averaging 730 cc/min, in all of the animals studied. In any single animal, there was less than an 8% change in cardiac output throughout the entire study period. Arterial blood pH, pOs, and pC0, were maintained within normal ranges throughout the studies; see Table 1. There was no consistent or significant change in pH or blood gases in any of the dogs throughout the three study periods. The ranges of the aortic, pulmonary arterial, left atrial, and right atria1 pressures encountered in the entire series during the study periods are depicted in Table 2. No consistent or significant changes in aortic, left atrial, or right atria1 pressure occurred between the high and low ranges of hematocrit. There was a statistically significant difference in the pulmonary arterial pressure

BLOOD VISCOSITY

AND PULMONARY

561

RESISTANCE

25

1

Fig. l.-Relationship of change in hematocrit in same animal to change in blood viscositv.

SHEAR RATE Isecnnds“l

encountered at the high hematocrit ranges as compared with the low hematocrit ranges. The heart rates of the animals during periods of study are also shown in Table 2. There was no significant difference in heart rate in any animal between the high and low hematocrit ranges. The ranges of systemic and pulmonary va’scular resistance and left and right ventricular stroke work are shown in Table 3. Because of the design and intent of the model, no significant difference in systemic vascular resistance was seen

Table l.-Ranges PH PO, PC% Cardiac output

of Blood Gases and Cardiac Output Throughout Study Periods in Entire Series 7.26 78 24

7.46 (average 7.38) -151 ( average 112 ) - 40 (average 33)

500-980 cc/min (average 730 cdmin)

( < 8% change in any animal)

562

TYSONETAL. Table 2.-Ranges of Mean Aortic, Pulmonary Arterial, and Left and Right Atria1 Pressures and Heart Rate Throughout Study Periods in Entire Series mPa0 mPpa mPla mPra Heart rate

82 -101 mm Hg (average 92 5 - 21 mm Hg (average 12.6 1.46.8 mm Hg (average 3.4 0.6 4.8 mm Hg (average 2.3 160-245 (average 196)

mm mm mm mm

Hg) Hg) Hg) Hg)

Table 3.-Ranges of Systemic and Pulmonary Vascular Resistance and Left and Right Ventricular Stroke Work Throughout Study Periods in Entire Series Rs (dyne set cm-s) Rp ( dyne set cm-5 ) LVSW ( g-m) RVSW (g-m)

2730-9408 (average 5816) 180-1056 (average 436) 28.1- 57.4 ( average 42.1) 1% 10.5 (average 4.4)

in any animal. Likewise, left ventricular stroke work did not change significantly during the study periods. Pulmonary vascular resistance and right ventricular stroke work, however, were both significantly increased at the higher hematocrit levels. The effects of changes in hematocrit, and hence blood viscosity, upon pulmonary vascular resistance when cardiac output is maintained constant are better depicted in Tables 4 and 5. Table 4 represents the changes seen in the six animals in which reservoir blood was exchanged first for isologous-packed red blood cells and then for isologous plasma. Table 5 represents the findings seen in those six animals in which the reservoir blood was initially exchanged for isologous plasma and then for isologous packed red blood cells. In each preparation, regardless of whether the hematocrit was initially raised or lowered, the direction of change in pulmonary vascular resistance was in the same direction as the change in hematocrit. In computer analysis of variance, the values from both groups are statistically significant at less than the 0.005 level. DISCUSSION The association of arterial hypoxemia and polycythemia has long been known. A number of studies have shown that a major determinant of blood viscosity is the blood hematocrit level and that increased blood viscosity results in a concomitant increase in systemic vascular resistance and a secondary diminution Table 4.-Changes in Pulmonary Vascular Resistance (Rp) in the Six Animals Which Hematocrit Levels Were First Elevated, Then Lowered

HCT 40% (range 31-48) Rp average 455 p (range 108-724)

Hey 54% ( 44-62 ) Change in Rp ( + 151 p) Range ( + 29 - +332) 1 HCT 19% ( 15-22) Change in Rp ( - 159 a) Range ( - 15-303)

in

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BLOODVISCOSITYANDPULMONARYRESISTANCE

Table 5.-Changes in Pulmonary Vascular Resistance (Rp) in the Six Animals in Which Hematocrit Levels Were First Reduced, Then Elevated.

HCT41% ( range 32-47 Rp average 430 p (range 216614)

Hc:T 46% ( 44-50 ) Change in Rp ( + 301 p ) Range ( + 67 - + 555 )

)

r \

HOT21% (N-29) ChangeinRp (- 114~) Range ( -30 - -228)

in cardiac output.3-7 The current studies indicate that changes in blood viscosity exert a direct influence on pulmonary vascular resistance and cannot be attributed solely to pulmonary vascular adaptation to changes in cardiac output. In the clinical utilization of systemic arterial-pulmonary artery shunts for cyanotic congenital heart disease, one might expect that persistent hypoxemia and polycythemia would result in both increased systemic vascular resistance and increased pulmonary vascular resistance. Though one would expect total cardiac output to be diminished, it seems unlikely that pulmonary blood flow would decrease proportionately more than does systemic blood flow. On the other hand, persistence of arterial hypoxemia sufficient to induce polycythemia following utilization of a superior vena caval right pulmonary artery shunt in the palliative management of cyanotic congenital heart disease may induce a particular hazard. Not only is total cardiac output decreased, but resistance to pulmonary blood flow is increased secondary to the increase in blood viscosity. It is conceivable that a cycle might be initiated whereby increased blood viscosity, through an increasing blood hematocrit, may induce increased pulmonary vascular resistance with an elevation in superior vena caval pressure, decreased pulmonary blood flow through the shunt because of increasing collateral blood flow between the superior and inferior vena caval systems, and further hypoxemia with a further increase in blood hematocrit. CONCLUSION

Blood viscosity exerts a direct effect upon pulmonary vascular resistance in the absence of any neural or cardiac variables, and the elevation of pulmonary vascular resistance seen in hyperviscous states cannot be attributed solely to reduction in cardiac output. Polycythemia may have a particularly deleterious effect upon the function of systemic venous-pulmonary artery shunts. REFERENCES 1. Eckstein, R. W., Book, D., and Gregg, D. E.: Blood viscosity under different experimental conditions and its effect on blood flow. Amer. J. Physiol. 135:772, 1941. 2. Wells, R. E., Jr., Denton, R., and Merrill, E. W.: Measurement of viscosity of

biologic fluids by a cone plate viscometer. J. Lab. Clin. Med. 57:646, 1961. 3. Replogle, R. L., Meiselman, H. J., and Merrill, E. W.: Clinical implications of blood rheology studies. Circulation 36: 148, 1967. 4. Richardson, T. Q., and Guyton, A. C.:

564 Effects of polycythemia and anemia on cardiac output and other circulatory factors. Amer. J. Physiol. 197:1167, 1959. 5. Replogle, R. L., Kundler, H., and Gross, R. E.: Studies on the hemodynamic importance of blood viscosity. J. Thorac. Cardiovast. Surg. 50:658, 1965. 6. Wells, R. E., Jr., and Merrill, E. W.:

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Influence of flow properties of blood upon viscosity hematocrit relationship. J. Clin. Invest. 41:1591, 1962. 7. Murray, J. F., Escobar, E., and Rapaport, E.: Effects of blood viscosity on hemodynamic responses in acute normovolemic anemia. Amer. J. Physiol. 216:638, 1969.