EFFECT OF GLUTATHIONE MONOETHYL ESTER ON GLUTATHIONE LEVEL AND CARDIAC ENERGETICS IN REPERFUSED PIG-HEART

The GSH level in myocardial tissue represents an important defense mec hanism against oxygen toxicity.since the ischemia-induced depletion of GSH might favour the cytotoxicity of oxygen-derived free radicals pro duced during reperfusion, we assessed the effects of the GSH donor glu tathione monoethylester,in anaesthetized pigs subjected to 90 minutes of coronary occlusion followed by 30 minutes reperfusion. The drug was infused intracoronarily at a dose of 1 mg/ml (0.5 ml/min) throughout the experimental period . After coronary occlusion and reperfusion, we found a decrease in GSH, ADP, ATP and phosphocreatine levels in reper fused compared with non-ischemic tissue. Less evident were the differe nces in mitochondrial function,there being only a reduction in the rep erfused tissue of the respiratory control index and state 3 respiratio n values when pyruvate was used as substrate. The infusion with glutat hione monoethylester decreased the depletion of tissue GSH and improve d the GSH/GSSG ratio, particularly in the non-ischemic tissue. Moreove r, the drug decreased the mitochondrial dysfunction at the level of py ruvate utilization and partially prevented the fall in ATP in the repe rfused tissue. This study confirms a possible protective effect of glu tathione monoethylester in the prevention of reperfusion-induced myoca rdial damage.