Changes in oxygen-haemoglobin affinity and myocardial function during extracorporeal perfusion in immature pigs

Abstract

An alteration in oxygen-haemoglobin affinity, as indicated by the partial pressure of oxygen at 50% haemoglobin saturation (P₅₀), may theoretically affect oxygen delivery to the myocardium and, thus, alter myocardial tissue PO₂ and possibly myocardial function. We studied the effect of changes in P₅₀ on heart function, metabolism, and coronary sinus PO₂ in 10 anaesthetized immature domestic pigs. To facilitate exchange transfusions and control of preload (left ventricular end diastolic pressure, LVEDP), afterload (mean arterial pressure), cardiac output, and heart rate, the animals were placed on right heart bypass. Stroke work (SW), myocardial oxygen consumption (MVO₂), coronary blood flow (CBF), arterial-coronary sinus O₂ content difference (CaO₂ -CcsO₂), and P₅₀ were measured with a control blood prime and after an exchange transfusion with blood having either a low (Group I) or high (Group II) affinity for oxygen. Results (Mean ± SEM, Control versus Test): P₅₀ (mmHg) at 37°C and pH 7.4 increased in Group 1 (35.5 ± 0.7 versus 40.1 ± 1.2, p <0.01) and decreased in Group II (34.7 ± 1.3 versus 26.3 ± 0.5, P <0.001). At 8mmHg LVEDP, SW (gram·metres, g.m) remained constant in Group I (12.2 ± 1.1 versus 11.7 ± 0.8 g·m), but decreased (p <0.05) in Group II (11.7 ± 0.9 versus 8.6 ± 0.61 g.m). In addition, Starling curves relating SW to LVEDP between 4 and 18mmHg were uniformly depressed in Group II but not Group I. No significant change in MVO₂ occurred in either group. Group II demonstrated decreased CaO₂- CcsO₂ (9.3 ± 0.8 versus 6.0 ± 0.3ml O₂/dl, p <0.05) and increased CBF (121.6 ± 16.5 versus 188.9 ± 16.9ml/min/1 00gm, p <0.01). PcsO₂ increased significantly in Group I (26.6 ± 4.2 versus 36.1 ± 2.7, P <0.02) but not Group II. In conclusion, a decrease in P₅₀ appeared to decrease myocardial function despite a lack of change in PcsO₂ or MVO₂. A decrease in P₅₀ also led to an increase in CBF. An increase in P₅₀ did not alter function, but did increase coronary sinus and, presumably, tissue PO₂.

Get full access to this article

View all access options for this article.

References

Benesch R. , Benesch RE The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin. Biochem Biophys Res Comm 1967; 26: 162-67.

Chanutin A. , Curnish RR Effect of organic and inorganic phosphates on the oxygen equilibrium of human erythrocytes. Arch Biochem Biophys 1967; 121: 96-102.

Dempsey JR , Thompson JM , Forster HV , Cerny FC , Chosy LW HbO2 dissociation in man during prolonged work in chronic hypoxia . J Appl Physiol 1975;38:1022-29.

Harken AH The surgical significance of the oxyhemoglobin dissociation curve . Surg Gynecol Obstet 1977; 144: 935-55.

Lenfant C. , Torrance J. , English E. et al. Effect of altitude on oxygen binding by hemoglobin and on organic phosphate levels. J Clin Invest 1968; 47: 2652—56.

Shappell SD , Murray JA , Nasser MG , Wills RE , Torrance JD , Lenfant Cjm. Acute changes in hemoglobin oxygen affinity during angina pectoris . New Engl J Med 1970; 282: 1219-24.

Taunton JE , Taunton CA , Banister EW Alterations in 2,3-DPG and P50 with maximal and submaximal exercise . Med Sci Sports 1974; 6: 238-41.

Young JA , Lichtman MA , Cohen J. Reduced red cell 2,3-diphosphoglycerate and adenosine triphosphate, hypophosphatemia, and increased hemoglobin-oxygen affinity after cardiac surgery . Circulation 1973; 47: 1313-18.

Rubinstein D. , Warrendorf E. An incubation medium for the elevation of adenosine triphosphate and 2,3-diphosphoglycerate in fresh and long preserved human erythrocytes. Can J Biochem 1975; 53: 671-78.

10.

Dennis RC , Hechtman HB , Berger RL , Vito L. , Weisel RD , Valeri CR Transfusion of 2,3-DPG enriched red cells to improve cardiac function . Ann Thorac Surg 1978; 26: 17-26.

11.

Willford DC , Hill EP , Moores WY Theoretical analysis of optimal P50. J Appl Physiol 1982; 52: 1043—48.

12.

Tenney SM A theoretical analysis of the relationship between venous blood and mean oxygen pressures. Resp Physiol 1974; 20: 283-96.

13.

Willford DC Shifted porcine oxygen-hemoglobin dissociation curves and theoretical oxygen delivery. Master's Thesis San Francisco State University, 1978.

14.

Beutler E. Red cell metabolism: a manual of biochemical methods. Second edition. Grune and Stratton, 1975.

15.

Neville JR Hemoglobin oxygen affinity measurement using biotonometry. J Appl Physiol 1974; 37: 967-71.

16.

Moores WY , Hannon JP , Crum JD , Willford DC Continuous and pulsatile extracorporeal perfusion in the beating and fibrillating swine myocardium: effects on left ventricular function. Surgical Forum 1977; 28: 262—64.

17.

Willford DC , Hill EP Modest effect of temperature on the porcine oxygen dissociation curve. Respir Physiol 1986 ; 64: 113-23.

18.

Willford DC , Hill EP Temperature corrections for blood gas values. In: Swine in biomedical research, volume 3. New York: Plenum Publishing Corporation, 1986: 1473-78.

19.

Kim HD , McManus TJ Studies on the energy metabolism of pig red cells. 1. The limiting role of membrane permeability in glycolysis. Biochem Biophys Acta 1971; 230: 1-11.

20.

Kim HD , McManus TJ. Studies on the energy metabolism of pig red cells. 2. Lactate formation from free ribose and deoxyribose with maintenance of ATP . Biochem Biophys Acta 1971; 230: 12-19.

21.

Beutler E. , Guinto E. Dihydroxyacetone metabolism by human erythrocytes: Demonstration of triokinase activity and its characterization. Blood 1973 ; 41 559—68.

22.

Nakao M. , Nakao T. , Tatbana M. , Yoshikawa H. Phosphorus metabolism in human erythrocyte. III. Regeneration of adenosine triphosphate in long-stored erythrocytes by incubation with inosine and adenine . J Biochem 1960; 47: 661-71.

23.

Tsuboi KK , Fukunaga K. Inorganic phosphate and enhanced glucose degradation by the intact erythrocyte . J Biol Chem 1965; 240: 2806-10.

24.

Rubinstein D. , Denstedt OF The metabolism of the erythrocyte. XIV. Metabolism of nucleosides by the erythrocyte. Can J Biochem Physiol 1956 ; 34: 927-37.

25.

McManus TJ , Borgese TA Effect of pyruvate on metabolism of inosine by erythrocytes. Fed Proc 1961; 20: 65.

26.

Minikami S. , Tomodu A. Intracellular pH and red cell 2,3-diphosphoglycerate . Proc Symp Chem Physio Pathol 1974; 14: 25-27.

27.

Salisbury PF , Cross CE , Rieben PA Distensibility and water content of heart muscle before and after injury. Circ Res 1960 ; 8: 788-93.

28.

Cross CE , Rieben PA , Salisbury PF Influence of coronary perfusion and myocardial edema on pressure-volume diagram of left ventricle. Am J Physiol 1961 ; 201: 102-108.

29.

Benesch RE , Triner L. , Benesch RE , Kwong S. , Verosky M. Enhanced oxygen unloading by an interdimerically crosslinked hemoglobin in an isolated rabbit heart. Proc Nat Acad Sci 1984; 81: 2941-43.

30.

Pantley GA , Oyama AA , Metcalfe J. , Lawson MS , Welch JE Improvement in the relationship between flow to ischemic myocardium and the extent of necrosis with glycolytic intermediates that decrease blood oxygen affinity in dogs. Circ Res 1981; 49: 395—404.

31.

Woodson RD , Wranne B. , Detter JC Effect of increased blood oxygen affinity on work performance in rats . J Clin Invest 1973; 52: 2717-24.