Superoxide dismutase therapy for myocardial ischemia.
Oxygen derived free radicals have been shown to be generated during reperfusion of ischemic myocardium by a variety of approaches including spin trap probes. Three levels of injury have been described for the reperfused heart. Periods of ischemia of only several minutes can trigger lethal arrhythmias on reperfusion. Anti-oxidants including SOD and or catalase, as well as iron chelators reduce the incidence of these arrhythmias in both dog and rat. Xanthine oxidase inhibitors are equipotent with SOD in this model suggesting that xanthine oxidase is the source of the radicals. Periods of occlusion lasting 10-15 minutes produce a recoverable defect in contractility termed "stunning". SOD plus catalase has been shown to reduce the incidence of stunning in a variety of models including the xanthine oxidase deficient rabbit. Neither agent on its own seemed to be effective against stunning in either the rabbit or the dog. Stunning is more difficult to demonstrate in the rabbit heart, presumably due to its lack of xanthine oxidase. Periods of ischemia in excess of 20 minutes will result in some irreversible cell death (infarction) with reperfusion. While studies using histochemical methods suggesting that SOD plus catalase given at the time of reperfusion could limit necrosis in the dog model, histological studies reveal that infarct size was not modified but rather, SOD appears to interfere with the ability of tetrazolium to histochemically discriminate between living and dead cells. While PEG SOD with its extended plasma half life was reported to reduce infarct size in the dog, it was unable to protect the reperfused rabbit heart. To date, none of the scavengers have been proven to limit infarction suggesting that free radicals contribute to arrhythmias and stunning, but do not kill cells in the reperfused heart.
Downey
J M
JM
Department of Physiology, University of South Alabama, Mobile 36688.
Omar
B
B
Ooiwa
H
H
McCord
J
J
D000818:Animals; D002374:Catalase / Q000627:therapeutic use; D003097:Collateral Circulation / Q000502:physiology; D003327:Coronary Disease / Q000188:drug therapy* / Q000517:prevention & control; D004195:Disease Models, Animal; D005609:Free Radicals; D006801:Humans; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology; D015203:Reproducibility of Results; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D005609:Free Radicals; D002374:Catalase; D013482:Superoxide Dismutase