EXOGENOUS REACTIVE OXYGEN SPECIES DEPLETE THE ISOLATED RAT-HEART OF ANTIOXIDANTS

The effects of reactive oxygen species (ROS) on myocardial antioxidant s and on the activity of oxidative mitochondrial enzymes were investig ated in the following groups of isolated, perfused rat hearts. I: Afte r stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xa nthine oxidase (XO) (25 U/I) and hypoxanthine (HX) (1 mM) as a ROS-pro ducing system (n = 7). III: Like group II, but recovered for 30 min af ter perfusion with XO + HX (n = 9). IV: The hearts were perfused and f reeze-clamped as in group III, but without XO + HX (n = 7). XO + HX re duced left ventricular developed pressure and coronary flow to approxi mately 50% of the baseline value. Myocardial content of hydrogen perox ide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX p erfusion, indicating that generation of ROS and lipid peroxidation occ urred. Levels of H2O2 and MDA normalized during recovery. Superoxide d ismutase, reduced glutathione and alpha-tocopherol were all reduced af ter ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q(10) (neither total, oxidized, nor reduced), cyt ochrome c oxidase, and succinate cytochrome c reductase. The present f indings indicate that the reduced contractile function was not correla ted to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more s ensitive to the action of oxidative injury. Copyright (C) 1996 Elsevie r Science Inc.