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Reduced free radical generation during reperfusion of hypothermically arrested hearts

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Abstract

Several studies indicate the presence of hydroxyl radical (OH·) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2 ) to a highly reactive and cytotoxic hydroxyl radical (OH·). In the present study, we have examined the generation of OH· and free iron in reperfused hearts following either normothermic (37°C) or hypothermic ischemia (5°C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37°C or 5°C and were then reperfused for 15 min at 37°C. The results of the study suggest that both the OH· generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5°C as compared to 37°C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2 at 5°C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH° and free iron as compared to 37°C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH· and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals.

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Abbreviations

OH·:

hydroxyl radical

O2 :

superoxide anion

ODFR:

oxygen-derived free radicals

KHB:

Krebs-Henseleit buffer

LDH:

lactate hydrogenase

SOD:

superoxide dismutase

References

  1. Rousou JA, Engelman RM, Breyer RH, Otani H, Lemeshow S and Das DK: The effect of temperature and hematocrit level of oxygenated cardioplegic solution on myocardial preservation. J Thorac Cardiovasc Surg 95: 625–630, 1988

    Google Scholar 

  2. Gay WA Jr: Potassium induced cardioplegia. Ann Thorac Surg 20: 95–100, 1975

    Google Scholar 

  3. Todd GJ and Tyers GFO: Amelioration of the effects of ischemic cardiac arrest by the intracoronary administration of cardioplegic solutions. Circulation 52: 1111–1117, 1975

    Google Scholar 

  4. Badeer N: Effect of hypothermia on oxygen consumption and energy utilization of heart. Circ Res 4: 523, 1956

    Google Scholar 

  5. McConnell DH, Brazier JA, Cooper N and Buckberg GD: Studies on the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. J Thorac Cardiovasc Surg 69: 95–101, 1976

    Google Scholar 

  6. Das DK, Engelman RM, Rousou JA and Breyer RH: Aerobic vs. anaerobic metabolism during ischemia in heart muscle. Ann Chir Gynaecol 76: 68–76, 1987

    Google Scholar 

  7. Arroyo CM, Kramer JH, Dickens BF and Weglicki WB: Identification of free radicals in myocardial ischemia/reperfusion by spin trapping with DMPO. FEBS Lett 221: 101–104, 1987

    Google Scholar 

  8. Das DK, Engelman RM, Rousou JA, Breyer RH, Otani H and Lemeshow S: Pathophysiology of superoxide radicals as potential mediators of reperfusion injury in pig heart. Basic Res Cardiol 81: 155–166, 1986

    Google Scholar 

  9. McCord JM: Oxygen derived free radicals in postischemic tissue injury. N Engl J Med 312: 159–163, 1988

    Google Scholar 

  10. Zweier JL: Measurement of superoxide derived free radicals in the reperfused heart. J Biol Chem 263: 1353–1357, 1988

    Google Scholar 

  11. Horton AA and Fairhurst S: Lipid peroxidation and mechanism of toxicity. Crit Rev Toxicol 18: 27–32, 1987

    Google Scholar 

  12. Kukreja RC, Okabe E, Schreier GM and Hess ML: Oxygen radical-mediated lipid peroxidation and inhibition of Ca2+ ATPase activity of cardiac sarcoplasmic reticulum. Arch Biochem Biophys 261: 447–457, 1988

    Google Scholar 

  13. Kramer JH, Mak T and Weglicki WB: Differential sensitivity of canine cardiac sarcolemmal and microsomal enzymes inhibited by free radical induced lipid peroxidation. Circ Res 55: 120–124, 1984

    Google Scholar 

  14. Prasad MR, Engelman RM, Jones RM and Das DK: Effects of oxyradicals on oxymyoglobin deoxygenation, haem removal, and iron release. Biochem J 263: 731–736, 1989

    Google Scholar 

  15. Halliwel B and Gutteridge JMC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219: 1–14, 1984

    Google Scholar 

  16. Liu X, Prasad MR, Engelman RM, Jones RM and Das DK: Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart. Am J Physiol 259: H1101-H1107, 1990

    Google Scholar 

  17. Starke PE and Farber JL: Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. J Biol Chem 260: 10099–10104, 1985

    Google Scholar 

  18. Hoffmann ME, Mello-Filho AC and Meneghini R: Correlation between cytotoxic effects of hydrogen peroxide and the yield of DNA strand breaks in cells of different species. Biochim Biophys Acta 781: 234–238, 1984

    Google Scholar 

  19. Otani H, Prasad MR, Jones RM and Das DK: Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts. Am J Physiol 257: H252-H258, 1989

    Google Scholar 

  20. Das DK, George A, Liu X and Rao PS: Detection of hydroxyl radical in the mitochondria of ischemic myocardium by trapping with salicylate. Biochem Biophys Res Commun 165: 1004–1009, 1989

    Google Scholar 

  21. Gutteridge JMC: Iron promoters of the Fenton reaction and lipid peroxidation can be released from haemoglobin by peroxides. FEBS Lett 201: 291–295, 1986

    Google Scholar 

  22. Badylak SE, Simmons A, Turek J and Babbs CF: Protection from reperfusion injury in the isolated rat heart by post-ischemic deferoxamine and oxypurinol administration. Cardiovasc Res 21: 500–506, 1987

    Google Scholar 

  23. Taylor DJ, Matthews PM and Radda GK: Myoglobin dependent oxidative metabolism in the hypoxic rat heart. Respir Physiol 63: 275–283, 1986

    Google Scholar 

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Renuka Prasad, M., Liu, X., Rousou, J.A. et al. Reduced free radical generation during reperfusion of hypothermically arrested hearts. Mol Cell Biochem 111, 97–102 (1992). https://doi.org/10.1007/BF00229579

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