THE CARDIOPROTECTIVE EFFECT OF GAMMA-GLUTAMYLCYSTEINE ETHYL-ESTER DURING CORONARY REPERFUSION IN CANINE HEARTS

1 The cardioprotective effect of gamma-glutamylcysteine ethyl ester was investigated on ischaemia-reperfusioninduced myocardial damage in anaesthetized dogs. 2 Open chest anaesthetized dogs were divided into four groups: 2 h occlusion of the left anterior descending coronary artery (LAD); 2 h LAD occlusion followed by 1 h reperfusion; 2 h LAD occlusion followed by 1 h reperfusion with administration of gamma-glutamylcysteine ethyl ester (10 mg kg-1 just before reperfusion); 2 h LAD occlusion followed by 1 h reperfusion with administration of GSH (the reduced form of glutathione, 10 mg kg-1 just before reperfusion). 3 After occlusion or reperfusion, heart mitochondria were prepared from the normal area and the occluded or the reperfused area, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically. 4 Mitochondrial GSH and GSSG (the oxidized form of glutathione) concentrations, and activities of glutathione peroxidase and glutathione reductase were measured. 5 Two h of LAD occlusion induced mitochondrial dysfunction with depletion of mitochondrial GSH concentration. One h of reperfusion after 2 h LAD occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration. 6 gamma-Glutamylcysteine ethyl ester reduced mitochondrial dysfunction and depletion of mitochondrial GSH concentration after 2 h LAD occlusion and 1 h reperfusion. In contrast, GSH did not prevent depletion of mitochondrial GSH concentration and mitochondrial dysfunction after 2 h LAD occlusion followed by 1 h reperfusion. 7 The activities of glutathione peroxidase and glutathione reductase did not change significantly in each group. 8 One h of reperfusion after 2 h occlusion of LAD induced ventricular arrhythmias. gamma-Glutamylcysteine ethyl ester markedly reduced the development of reperfusion arrhythmias, whilst GSH showed no protective effect. 9 gamma-Glutamylcysteine ethyl ester maintained mitochondrial GSH concentration, prevented reperfusion myocardial damage, and reduced reperfusion arrhythmias.