Captopril Therapy Limits Ventricular Remodeling But Does Not Alter Myocardial Collagen Fiber Morphology of Cardiomyopathic Hamsters

Abstract

Previous studies of the effect of angiotensin-converting enzyme (ACE) inhibitors on the process of cardiac remodeling have devoted little attention to potentially beneficial alterations in collagen fiber morphology and microscopic organization. The present work is part of a continuing effort to define mechanisms responsible for changes in microscopic material properties of cardiac tissue that are induced by such pharmacologic therapy. Morphologic evaluation of 11 cardiomyopathic (CM) and 5 control hamsters was performed. Six CM hamsters received captopril for 3 months in their drinking water (2 gm/l), and five other CM hamsters and five normal control hamsters received no treatment. Myocyte and collagen content, organization, and fiber size were defined with the use of circular statistics in fixed sections that were stained with picrosirius red and viewed with polarized light. The scar regions from both treated and untreated CM hearts manifested similar collagen fiber thicknesses, organization (angular deviation 21.1 ± 0.7 degrees vs. 19.2 ± 2.2 degrees, untreated vs. treated, p = NS), and content (65.0% ± 2.2% vs. 65.7% ± 3.7%, untreated vs. treated, p = NS). However, significant muscle fiber disarray was observed in myocytes in the non-necrotic zones near scars for both treated and untreated CM heart, and a strong trend toward normalization of myocyte alignment was observed after captopril therapy. In the present study, captopril exerted no significant effect on collagen content, two-dimensional fiber organization, or fiber thickness in either scar or nonscar regions. Thus, the beneficial effects of captopril on cardiac material properties in ventricular remodeling associated with heritable cardiomyopathy does not appear to be related to alterations in collagen fiber morphology or organization. However, the trend toward normalization of myocyte alignment induced by captopril in non-necrotic zones suggests a possible mechanism for the known beneficial effects of captopril on favorable ventricular remodeling.