NICORANDIL SUPPRESSED VENTRICULAR ARRHYTHMIAS IN A CANINE MODEL OF MYOCARDIAL-ISCHEMIA

These experiments were designed to explore the possibility that a K+ c hannel opener which also donates nitric oxide to the myocardium (nicor andil) may modify ischaemia-induced ventricular arrhythmias in a large animal model. In mongrel dogs anaesthetised with chloralose-urethane and thoracotomised, a side branch of the left anterior descending arte ry was catheterised for the local intracoronary infusion of nicorandil (2.5 mu g kg(-1) min(-1) for 20 min prior to coronary artery occlusio n and then continuing throughcut the 25 min occlusion period). In this dose, nicorandil had no haemodynamic effects, increased coronary bloo d now by up to 16% and significantly reduced the severity of ischaemia -induced arrhythmias (e.g. from nearly 500 ventricular premature brats in the controls to 160 +/- 60 in the nicorandil group). There was a s ignificant reduction in the number of episodes of ventricular tachycar dia during tile ischaemic period and a reduced incidence of ventricula r fibrillation following reperfusion resulting in a 42% survival from the combined ischaemia-reperfusion insult (cf. 0% in the control; P < 0.05). The marked changes that occurred in ST-segment elevation (mappe d with epicardial electrodes) and in the inhomogeneity of electrical a ctivation within the ischaemic area in control dogs was markedly reduc ed in those dogs administered nicorandil. We conclude that the local i ntracoronary administration of nicorandil reduces the severity of both ischaemia and the life-threatening arrhythmias that result from an ab rupt reduction in coronary blood flow in this canine model. Possible m echanisms include an increase in coronary blood flow, a reduction in t he severity of myocardial ischaemia and an ability of the compound to 'donate' nitric oxide to the ischaemic area.