E and the heart: Possible role as antioxidant. Acta Vitaminol. Enzymol. 5: 11-22, ) Jolly, S. R., Kane, W. J., Bailie, M. B. et al.

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5 1) Ferrari, R., Visoli, O., Guarnieri, C. et al.: Vitamin E and the heart: Possible role as antioxidant. Acta Vitaminol. Enzymol. 5: 11-22, ) Jolly, S. R., Kane, W. J., Bailie, M. B. et al.: Canine myocardial reperfusion injury. Its reduction by the combined administration of superoxide dismutase and catalase. Circ. Res. 54: , ) Stewart, J. R., Crute, S., Loughlin, V. et al.: Preven- of free radical-induced myocardial tion reperfusion injury with allopurinol. J. Thorac. Cardiovasc. Surg. 90: 68-72, ) Manning, A. S. and Cortart, D. J.: Ischemic and reperfusion induced arrhythmias in the rat heart: Ef- fects of xanthine oxidase inhibition with allopurinol. Circ. Res. 55: , ) Granger, D. N., Rutili, G., McCord, J. et al.: Superoxide radicals in feline intestinal ischemia. Gastroen- terology 81: 22-29, ) Das, D. K. and Neogi, A.: Effects of superoxide anions on the (Na+K) ATPase system in rat lung. Clin. Physiol. Biochem. 2: 32-38, ) Kuehl, F. A., Jr. and Egan, R. W.: Prostaglandins, arachidonic acid and inflammation. Science 210: , tion by human neutrophils. Can. J. Physiol. Pharmacol. 60: , ) Engler, R. L., Schmid-Schonbein, G. W. and Pavelec, R. S.: Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog. Am. J. Pathol. 111: , ) Boveris, A.: Mitochondorial production of superoxide radical and hydrogen peroxide. Adv. Exp. Med. Biol. 78: 67-82, ) McCord, J. M. and Fridovich, I.: Superoxide dismutase. An enzymatic function for erythrocuperin. J. Biol. Chem. 244: , ) Guanieri, C., Flamigni, F. and Caldarera, C. M.: Role of oxygen in the cellular damage induced by re- of the hypoxic heart. J. Mol. Cell. Car- oxygenation diol. 12: , ) Gauduel, Y. and Duvelleroy, M. A.: Role of oxygen radicals in cardiac injury due to reoxygenation. J. Mol. Cell. Cardiol. 16: , ) Tyler, D. D.: Role of superoxide radicals in the lipid peroxidation of intracellular membrane. FEBS Lett. 51: , 1975.

6 16) Woodward, B. and Zakaria, M. N. M.: Effect of some free radical scavengers on reperfusion induced arrythmias in the isolated rat heart. J. Mol. Cell. Cardiol. 17: , ) Ysebaert-Vanneste, M., Vanneste, W. H. and Mason, H. S.: An anomalous ESR signal from rapidly frozen liver microscrosomes. Biochim. Biophys. Acta 267: , ) Buettner, G. R.: Spin trapping: ESR parameters of spin adducts. Free Radical Biol. Med. 3: , ) Arroyo, C. M., Kramer, J. H., Weglicki, W. B. et al.: Identification of free radical ischemia/reperfusion by spin trapping with nitrone DMPO. FEBS Lett. 221: , ) Garlick, P. B., Davies, M. J., Slater, T. F, et al.: Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy. Circ. Res. 61: , ) Gauduel, Y. and Duvelleroy, M. A.: Role of oxygen radicals in cardiac injury due to reoxygenation. J. Mol. Cell. Cardiol. 16: , ) Rao, P. S., Cohen, M. V. and Mueller, H. S.: Production of free radicals and lipid peroxides in early experimental myocardial ischemia. J. Mol. Cell. Cardiol. 15: , ) Lazar, H. L., Buckberg, G. D., Manganaro, A. J. et al.: Reversal of ischemic damage with secondary blood cardioplegia. J. Thorac. Cardiovasc. Surg. 78: , ) Michelson, A. M. and Puget, K.: Cell penetration by exogenous superoxide dismutase. Acta Physiol. Scand 492 (Suppl.): 67-80, Myocardial Protection with Differences of Administration Method of Human Superoxide Dismutase on Reperfusion Injury Noriyoshi YAMAMOTO, Eiji IKEDA, Masahiko TAKEO, Yorikazu NAKAYAMA*, Yoshimasa SENOO* and Shigeru TERAMOTO (Department of Surgery II, and Cardiovascular Surgery*, Okayama University of Medical School, Okayama, Japan) To investigate the efficacy of human superoxide dismutase (h-sod) in myocardial ischemia and reperfusion with difference of administration of h-sod, twenty four dogs were subjected to 120 min ischemia by the cross clamping of the ascending aorta, and followed by 60min reperfusion, The dogs were randomly assigned to three groups: group G, h-sod (8mg/kg) was injected into the cardiopulmonary bypass (CPB) circuit 5min prior to reperfusion; group L, h-sod (3mg/kg) was administered by bolus injection through the aortic root into the coronary artery 1min prior to reperfusion; group C, nothing was administered. The values of creatinine phosphate MB isozyme (CPK-MB) and a-hydroxydehydrogenase (HBD) in coronary effluent, and lipid peroxides (LPO) in coronary artery and sinus blood, were measured during CPB. Cardiac function was evaluated by cardiac index (C. I.) and LV max dp/dt, and it was expressed as a percent recovery of pre-cpb state. Myocardial water contents as myocardial edema were measured after CPB. Effluents of CPK-MB and HBD at 60min after reperfusion were less in group L than group G, C. Generations of LPO (A-Cs difference) were less at 5min after reperfusion in group G, L than group C and there were significant differences between group G, L and group C. The percent recovery of C. I. and LV max dp/dt at 60min after reperfusion was superior in group G, L than group C and there were significant difference between group G, L and group C. Myocardial water contents at 60min after reperfusion were less in group G, L than group C and there were significant difference between group G, L and group C. In the lipid peroxides generation, cardiac function and myocardial edema except effluents of cardiac enzymes, group G was as well as group L. These data suggest that the injection of h-sod into the CPB circuit just before reperfusion is effective to prevent the reperfusion injury as well as the administra-

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