TRANSITION-METAL CHELATORS REDUCE DIRECTLY MEASURED MYOCARDIAL FREE-RADICAL PRODUCTION DURING REPERFUSION

Transition metals such as iron and copper are present in the myocardiu m and can act as catalysts for the formation of oxygen free radicals d uring reperfusion after myocardial ischemia. Previous studies suggeste d that transition metal chelators such as desferrioxamine reduce the p roduction of such radicals and may thereby attenuate postischemic myoc ardial dysfunction. These studies used spin trapping agents, commonly nitrone compounds, which may themselves influence the severity of the ischemia and reperfusion events being studied. We evaluated two transi tion metal chelators, desferrioxamine, an iron chelator, and bathocupr oine, a copper chelator, by using a new electron paramagnetic resonanc e technique that does not require the administration of spin traps. We measured ascorbate free radical, an index of free radical production, in the great cardiac vein effluent. Twenty-eight open-chest dogs unde rwent 20 min of coronary artery occlusion and 30 min of reperfusion. T en dogs received no drug, 10 dogs received 750 mg bathocuproine, i.v.. and eight dogs received 700 mg desferrioxamine, i.v. Both bathocuproi ne and desferrioxamine blunted the postreperfusion increase in ascorba te free radical generation: no drug, 36 +/- 8% increase; desferrioxami ne, 13 +/- 5% increase; bathocuproine, 21 +/- 6% increase (p < 0.05 vs , baseline). Thus direct free radical measurements indicate that chela tion of the transition metals iron and copper reduces free radical gen eration during reperfusion.