A protective effect of sulphinpyrazone against coronary occlusion-induced shortening of myocardial refractory periods in the rat

Abstract

The hearts of anaesthetized, artificially ventilated rats were exposed, and the left coronary artery occluded. The diastolic threshold voltage for stimulation (DTV), the duration of the bipolar electrogram (DBE) and the functional refractory period (FRP) of the ischaemic area were measured at minute intervals for an hour after occlusion. Coronary occlusion caused a rise in DTV, a prolongation of the DBE and a biphasic change in the FRP, with an initial prolongation phase (1-4 min) followed by a decline to below pre-occlusion values (5-15 min). Episodes of ventricular tachyarrhythmia (VT) were most frequent during the period 5-15 min after the onset of occlusion of the coronary artery. This coincided with the period when FRP was minimal and the difference between DBE and FRP was maximal. Pretreatment of rats with sulphinpyrazone (2.5-40 mg kg-1) or indomethacin (5-20 mg kg-1) protected against the episodes of coronary occlusion-induced VT and against the associated decline in FRP of the ischaemic muscle. Sulphinpyrazone was more effective than indomethacin in this respect and a combination of the two drugs was approximately as effective as sulphinpyrazone alone. It was concluded that sulphinpyrazone protects rats against coronary occlusion-induced episodes of VT by reducing the risk of ventricular action potential re-entry. This effect is probably due to protection against the ischaemia-induced shortening of the myocardial FRP.