VENTRICULAR REMODELING - INSIGHTS FROM PHARMACOLOGICAL INTERVENTIONS WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS

Structural remodeling of the left ventricular (LV) myocardium develops in a time-dependent fashion following acute myocardial infarction and may be an integral component in the transition toward overt heart fai lure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular leve l, the remodeling process is associated with myocyte slippage, hypertr ophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monoth erapy with the angiotensin converting enzyme (ACE) inhibitor, enalapri l, on the progression of LV remodeling in dogs with LV dysfunction (ej ection fractions 30-40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy wit h enalapril (n = 7) or to no treatment (n = 7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) an d chamber sphericity increased significantly during the 3 months follo w-up period. In contrast, in dogs treated with enalapril ESVI, EDVI an d chamber sphericity remained essentially unchanged. Treatment with en alapril attenuated myocyte hypertrophy and the accumulation of interst itial collagen in comparison to untreated dogs. These data indicate th at early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibi tion of direct action of angiotensin-II and possibly the decrease in b radykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling.