Transition metal chelators reduce directly measured myocardial free radical production during reperfusion

Transition metals such as iron and copper are present in the myocardium and can act as catalysts for the formation of oxygen free radicals during reperfusion after myocardial ischemia. Previous studies suggested that transition metal chelators such as desferrioxamine reduce the production of such radicals and may thereby attenuate postischemic myocardial 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 transition metal chelators, desferrioxamine, an iron chelator, and bathocuproine, a copper chelator, by using a new electron paramagnetic resonance 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 underwent 20 min of coronary artery occlusion and 30 min of reperfusion. Ten dogs received no drug, 10 dogs received 750 mg bathocuproine, i.v., and eight dogs received 700 mg desferrioxamine, i.v. Both bathocuproine and desferrioxamine blunted the postreperfusion increase in ascorbate free radical generation: no drug, 36+/-8% increase; desferrioxamine, 13+/-5% increase; bathocuproine, 21+/-6% increase (p < 0.05 vs. baseline). Thus direct free radical measurements indicate that chelation of the transition metals iron and copper reduces free radical generation during reperfusion.