Early administration of Enalapril prevents diastolic dysfunction and ventricular remodeling in rabbits with myocardial infarction.

Abstract

We aimed to investigate the role of early administration of Enalapril (Enal) on post-myocardial infarction (MI) ventricular remodeling and diastolic dysfunction in rabbits. White New Zealand rabbits that underwent coronary artery ligature or Sham were divided in three experimental groups: (1) Sham, (2) MI, and (3) MI+Enal. Enal was given by gavage at a dose of 10mg/kg/day starting at 3h after surgery for 35days. At the end of the protocol, we measured (1) mean arterial pressure, (2) left ventricular (LV)+dP/dtmax, (3) LV end-diastolic pressure (LVEDP) and isovolumic relaxation (Tau), (4) LV dimensions, (5) LV ejection and shortening fraction, (6) infarct size (Masson's trichrome-stained slices), (7) fibrosis in the infarct and remote zone (Picrosirius red-stained slices), and (8) myocyte cross-sectional area (MCSA) in WGA-stained section. Enal reduced the mean arterial pressure by 30% as compared with untreated animals and Sham (P<.05). MI reduced LV+dP/dtmax and LV-dP/dtmax (mmHg/s), increased LVEDP (mmHg), Tau (ms), and t50 (ms) values, suggesting a decrease in the relaxation rate. LV end-diastolic dimension and LV end-systolic dimension (LVESD, mm) increased in untreated MI (P<.05 vs. Sham). In contrast, Enal markedly prevented post-MI diastolic dysfunction by significantly decrease LVEDP from 8.2±0.2 to 5.1±0.3mmHg, Tau from 19.8±0.8 to 15.3±0.9ms, and t50 from 12.4±0.5 to 9.6±0.8ms as well as reduced LVESD from 15±1.1 to 12±0.8mm (P<.05 MI vs. MI+Enal). Collagen concentration in the scar was unaffected, but chronic treatment with Enal prevented myocardial fibrosis and MCSA in the remote zone. In summary, chronic early administration of Enal to rabbits with experimental MI has a favorable effect on ventricular remodeling and diastolic function by reducing MCSA and fibrosis, without affecting the wound healing.