Ventricular remodeling: insights from pharmacologic 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 failure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular level, the remodeling process is associated with myocyte slippage, hypertrophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monotherapy with the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the progression of LV remodeling in dogs with LV dysfunction (ejection fractions 30-40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with enalapril (n = 7) or to no treatment (n = 7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and chamber sphericity increased significantly during the 3 months follow-up period. In contrast, in dogs treated with enalapril ESVI, EDVI and chamber sphericity remained essentially unchanged. Treatment with enalapril attenuated myocyte hypertrophy and the accumulation of interstitial collagen in comparison to untreated dogs. These data indicate that early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibition of direct action of angiotensin-II and possibly the decrease in bradykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D004656:Enalapril / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy / Q000473:pathology*; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D011897:Random Allocation; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000473:pathology*; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D003094:Collagen