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

PURPOSE: To investigate the influence of angiotensin-converting enzyme inhibitor (ACEI) on cardiac innervation and inducible ventricular arrhythmias (VAs) in healed myocardial infarction (MI). METHODS: 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. RESULTS: 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. CONCLUSION: In this study, prolonged captopril treatment was effective in preventing VAs in healed MI, partly by attenuating the spatial heterogeneity of cardiac innervation.