Regional denervation after myocardial infarction and its effect on ventricular repolarization

Abstract

To investigate whether myocardial infarction (MI) causes heterogeneity of sympathetic innervation and to evaluate the effects of sympathetic stimulation on myocardial repolarization in the regions of denervation after MI. Fourteen dogs were randomly divided into 2 equal groups: MI Group, undergoing ligation of the left anterior descending coronary artery, and Control Group, undergoing sham operation. Four weeks later thoracotomy was performed for the second time, the effective refractory period (ERP) of the non-infarcted myocardium at the base of heart proximal to the infarcted myocardium and the ERP of the non-infarcted myocardium at the cardiac apex distal to the infarcted myocardium by S(1)S(2) programmed stimulation. Then the left satellite ganglion was exposed, ligated, cut, and stimulated at the proximal end, and ERP was determined at the above mentioned regions again. After the ERP measurement the heart was taken out to undergo immunohistochemistry to observe the distribution of tyrosine hydroxylase (TH) positive nerve fibers. The ERP of the non-infarcted myocardium at the base of heart proximal to the infarcted myocardium was not significantly different from that of the non-infarcted myocardium at the cardiac apex distal to the infarcted myocardium before sympathetic stimulation in both groups. In MI Group, however, the ERP of the non-infarcted myocardium at the base of heart proximal to the infarcted myocardium was significantly shortened after stimulation at the satellite ganglion (141 ms +/- 10 ms) in comparison with that before the stimulation (162 ms +/- 9 ms, P < 0.01); and the ERP of the non-infarcted myocardium at the cardiac apex distal to the infarcted myocardium after sympathetic stimulation (157 ms +/- 8 ms) was not significantly different from that before sympathetic stimulation (161 ms +/- 6 ms), however, was significantly longer than that of the non-infarcted myocardium at the base of heart proximal to the infarcted myocardium (P < 0.05). In Control Group the ERP values of both the basal and apical regions were significantly shorter than those before stimulation at the same region (both P < 0.01), however, there were no significant differences in the ERP values at the same region before and after the stimulation for the 2 regions. Immunohistochemistry showed that TH positive nerve fibers were distributed in the whole heart of Control Group and in the heart base of MI Group, and no TH positive nerve fiber was seen in the cardiac apex of MI Group. Regional denervation occurs after MI; Spatial variation of regional sympathetic innervation leads to heterogeneity in cardiac repolarization after sympathetic stimulation.