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

Clin Invest Med. 2008;31(4):E198-205. doi: 10.25011/cim.v31i4.4780.

Abstract

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.

MeSH terms

  • Administration, Oral
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Arrhythmias, Cardiac / drug therapy*
  • Arrhythmias, Cardiac / pathology
  • Captopril / administration & dosage*
  • Captopril / pharmacology
  • Electrophysiology
  • Heart Ventricles / drug effects*
  • Heart Ventricles / innervation
  • Heart Ventricles / pathology
  • Immunohistochemistry
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / pathology
  • Nerve Fibers / drug effects*
  • Nerve Fibers / pathology
  • Placebos
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Placebos
  • Captopril