Effect of pindolol on neurosympathetic responsiveness, blood flow variability, and conduction in acutely ischaemic myocardium: the importance of heart rate

The effects of a beta-adrenoceptor antagonist with partial agonist activity (pindolol) were assessed in the open-chest anaesthetised dog during 12-minute periods of left anterior descending coronary artery (LAD) occlusion and reperfusion before and after sympathetic stimulation. Regional myocardial catecholamine efflux, blood flow, and epicardial activation abnormalities were assessed in three groups. In a control group (n = 8), two periods of ischaemia resulted in reproducible intraexperimental changes in catecholamine responses, blood flow, conduction abnormalities, and arrhythmias. Intravenous (i.v.) pindolol (0.45 mg/kg before the second occlusion) reduced nerve-stimulated norepinephrine (NE) overflow from nonischaemic (NI) myocardium but did not modify overflow from ischaemic (I) myocardium either during ischaemia or reperfusion. At constant heart rate (atrial pacing, n = 8), pindolol reduced absolute blood flow to I and NI but had no effect on the ratio of endocardial/epicardial blood flow, arrhythmias, or activation abnormalities during occlusion. Following a reduction in heart rate of 32 +/- 6 beats/min (no pacing, n = 8), pindolol resulted in similar reduction in blood flow to I and NI but also increased the ratio of endocardial/epicardial flow and reduced both spontaneous arrhythmias and activation delay during occlusion. The acute effects of pindolol on conduction abnormalities, arrhythmias, and blood flow distribution in I are thus dependent on reduction in heart rate.