The effect of exaprolol (MG 8823) on epicardial ST-segment changes in a feline model of acute myocardial ischaemia.

A model is described (anaesthetized, open-chest cats subjected to acute coronary artery occlusion) which allows the effects of drug interventions to be determined on one major electrocardiographic index of myocardial ischaemia. Epicardial ST-segment changes were continuously recorded from five individual sites on the surface of the left ventricle. Coronary artery occlusion (left anterior descending branch) resulted in marked and consistent elevations of the ST-segment in all sites in nearly all experiments. These changes started within 1 min of the onset of ischaemia and reached a peak at between 30 and 60 min; thereafter there was a gradual reduction over the next 4 h. The one significant haemodynamic effect of coronary artery occlusion was an increase in left ventricular (LV) end-diastolic pressure (LVEDP). Ventricular ectopic activity was not pronounced in this model (about 50 ectopic beats over the initial 30 min post-occlusion period). Exaprolol (1.0 mg kg-1, intravenously) a potent beta-adrenoceptor blocking agent with 'membrane stabilising activity', when given 1 h after the onset of ischaemia, reduced heart rate and LV dP/dtmax and increased LVEDP. These effects were prolonged (i.e. little recovery in heart rate 3 h after administration). Exaprolol decreased total ST-segment elevation immediately after administration; this was significantly different from the effect of intravenous saline and lasted for at least 3 h. The effects appeared to be greater at sites of less pronounced ischaemia. Intramyocardial temperature records were taken to indicate a reduction in blood flow to the ischaemic region; however the alleviation of epicardial ST-segment elevation suggests an improved myocardial oxygen demand:supply ratio. Reperfusion was unsuccessfully attempted after a 4 h occlusion period; reperfusion after a shorter period (30 min) resulted in ventricular ectopic activity but no fibrillation.