Effects of sympathetic stimulation, with and without previous 1 and adrenoceptor blockade, on refractoriness dispersion in canine heart

Abstract

The aim was to determine the electrophysiological effects of cardiac sympathetic stimulation, with and without prior alpha 1 and beta adrenoceptor blockade during myocardial ischaemia in dogs. Chloralose anaesthetised dogs were studied 2 h after ligation of the obtuse marginal branches of the circumflex artery (OMB). The refractory period was measured at eight sites in the ischaemic zone, two sites in the border zone, and two sites in the normal zone with S1-S2 extrastimulus methods. In group 1 (n = 13), before OMB ligation, stimulation of the ventrolateral cardiac nerve shortened the refractory period only in the ischaemic zone (p < 0.01). OMB ligation resulted in a significant shortening of the refractory period in the ischaemic zone (p < 0.01). In group 2 (n = 12), the alpha 1 blocker bunazosin (0.2 mg.kg-1, intravenously) blunted the shortening of the refractory period in the ischaemic zone induced by OMB ligation (p < 0.01), resulting in a reduction in refractory period dispersion between the ischaemic and non-ischaemic (border and normal) zones. Subsequent administration of the beta blocker propranolol (0.2 mg.kg-1, intravenously) prolonged refractory periods both in the ischaemic and in the non-ischaemic zones (p < 0.05 v p < 0.001). Ventrolateral cardiac nerve stimulation reversed the effects of bunazosin on the refractory period in the ischaemic zone; however, after the addition of propranolol, neural stimulation no longer influenced the refractory period. In group 3 (n = 13), propranolol (0.2 mg.kg-1, intravenously) reversed the shortening of the refractory period in the ischaemic zone (p < 0.01) induced by OMB ligation but also prolonged the refractory period in the non-ischaemic zone (p < 0.001); refractory period dispersion between the ischaemic and non-ischaemic zones was thus not reduced. Ventrolateral cardiac nerve stimulation had no effect on refractory period after administration of propranolol alone or propranolol followed by bunazosin. Although an alpha 1 blocker may be better than a beta blocker in reducing refractory period dispersion between the ischaemic and non-ischaemic myocardium, a beta blocker may protect more effectively than an alpha 1 blocker against the detrimental effects of cardiac nerve activity on electrical instability in the ischaemic myocardium.