VENTRICULAR ARRHYTHMIAS INDUCED BY ISCHEMIA-REPERFUSION ARE UNAFFECTED BY MYOCARDIAL GLUTATHIONE DEPLETION

Reduced glutathione (GSH) is a major myocardial antioxidant, Since rep erfusion phenomena such as ventricular fibrillation (VF) are associate d with oxygen free radical production during ischaemia, myocardial GSH depletion might be expected to increase susceptibility to such phenom ena. This possibility was tested in isolated rat hearts using diethylm aleate (DEM) or L-buthionine-SR-sulfoximine (BSO) to deplete myocardia l GSH. High dose DEM (860 mg/kg) depleted myocardial GSH from a contro l mean of 7.64 +/- 0.73 to 3.18 +/- 0.56, low dose DEM (215 mg/kg) to 4.29 +/- 0.53 nmol/mg protein and BSO (4 mmol/kg) from a control mean of 6.94 +/- 0.54 to 2.18 +/- 0.14 nmol/mg protein. Hearts were perfuse d in the Langendorff mode at 37 degrees C with bicarbonate buffer (K= 4.3 mM). Regional ischaemia was induced for 5, 8.5, 10, 20 or 40 min (DEM groups: n = 10/treatment/time point) or 8.5 min only (BSO groups : n = 10/treatment) then hearts were reperfused for 5 min. Reperfusion VF incidence showed a classical ''bell-shaped'' curve, but there was no difference in VF incidence, VF time-to-onset, arrhythmia duration a nd ''arrhythmia scores'' between GSH-depleted and control hearts. Depl eting myocardial GSH is not proarrhythmic for reperfusion-induced arrh ythmias. It would appear GSH is not significantly involved in protecti ng against the oxidant stress of reperfusion, or conversely that the r eserve of this redox system is so high only severe depletion might sho w an effect. (C) 1996 Academic Press Limited