Effects of angiotensin converting enzyme inhibition on cardiac innervation and ventricular arrhythmias after myocardial infarction

Abstract

To investigate the influence of angiotensin-converting enzyme inhibitor (ACEI) on cardiac innervation and inducible ventricular arrhythmias (VAs) in healed myocardial infarction (MI). Left anterior descending coronary artery was ligated to induce MI in 30 rabbits. After oral captopril (10mg/kg/d) for 8 weeks, electrophysiological study was performed to evaluate the incidence of inducible VAs. RT-PCR and immunohistochemistry were used to measure the cardiac innervation. Eight weeks after the operation, the incidence of inducible VAs in the MI-placebo group was higher (58.3%, 7/12) than in the sham operation group (16.7%, 2/12, P < 0.05). However, the incidence of inducible VAs in the MI-captopril group was lower (27.2%, 3/11) than in the MI-placebo group (P < 0.05). Proliferation and growth of nerve fibres in the MI-placebo group were mainly distributed at the periphery of the infarcted and perivascular regions of the myocardium. The density of nerve fibres increased in the MI-placebo group (3889+/-521 microm2/mm2) compared with the sham group (1727+/-304 microm2/mm2, P < 0.01) at the infarct border. In the MI-captopril group, the density of nerve fibres (3507+/-433 microm2/mm2) at the infarct border did not differ from that in the MI-placebo group (P=0.07). MI-induced abnormal nerve fibre distribution was partly restored by captopril treatment. In this study, prolonged captopril treatment was effective in preventing VAs in healed MI, partly by attenuating the spatial heterogeneity of cardiac innervation.