title: Ventricular arrhythmias induced by ischaemia-reperfusion are unaffected by myocardial glutathione depletion.
abstract: Reduced glutathione (GSH) is a major myocardial antioxidant. Since reperfusion phenomena such as ventricular fibrillation (VF) are associated with oxygen free radical production during ischaemia, myocardial GSH depletion might be expected to increase susceptibility to such phenomena. This possibility was tested in isolated rat hearts using diethylmaleate (DEM) or L-buthionine-SR-sulfoximine (BSO) to deplete myocardial GSH. High dose DEM (860 mg/kg) depleted myocardial GSH from a control 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 perfused 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 and "arrhythmia scores" between GSH-depleted and control hearts. Depleting myocardial GSH is not proarrhythmic for reperfusion-induced arrhythmias. It would appear GSH is not significantly involved in protecting against the oxidant stress of reperfusion, or conversely that the reserve of this redox system is so high only severe depletion might show an effect.
authors.affiliation: Rayne Institute, St Thomas' Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Connaughton
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
authors.forename: P S
authors.initials: PS
authors.lastname: Haddock
authors.forename: D J
authors.initials: DJ
authors.lastname: Hearse
authors.forename: M J
authors.initials: MJ
authors.lastname: Shattock
mesh_terms: D000818:Animals; D019328:Buthionine Sulfoximine / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency*; D008297:Male; D008298:Maleates / Q000378:metabolism; D015425:Myocardial Reperfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000378:metabolism*; D016276:Ventricular Function
chemical_list: D008298:Maleates; D019328:Buthionine Sulfoximine; C014476:diethyl maleate; D005978:Glutathione