CAPTOPRIL THERAPY LIMITS VENTRICULAR REMODELING BUT DOES NOT ALTER MYOCARDIAL COLLAGEN FIBER MORPHOLOGY OF CARDIOMYOPATHIC HAMSTERS

Previous studies of the effect of angiotensin-converting enzyme (ACE) inhibitors on the process of cardiac remodeling have devoted little at tention to potentially beneficial alterations in collagen fiber morpho logy and microscopic organization. The present work is parr of a conti nuing effort to define mechanisms responsible for changes in microscop ic material properties of cardiac tissue that are induced by such phar macologic therapy. Morphologic evaluation of 11 cardiomyopathic (CM) a nd 5 control hamsters was performed. Six CM hamsters received captopri l for 3 months in their drinking water (2 gm/l), and five other CM ham sters and five normal control hamsters received no treatment. Myocyte and collagen content, organization, and fiber size were defined with t he use of circular statistics in fixed sections that were stained with picrosirius red and viewed with polarized light. The scar regions fro m both treated and untreated CM hearts manifested similar collagen fib er thicknesses, organization (angular deviation 21.1 +/- 0.7 degrees v s. 19.2 +/- 2.2 degrees, untreated vs. treated, p = NS), and content ( 65.0% +/- 2.2% vs. 65.7% +/- 3.7%, untreated vs. heated, p = NS). Howe ver, 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 obs erved after captopril therapy. In the present study, captopril exerted no significant effect on collagen content, two-dimensional fiber orga nization, 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 n ot appear to be related to alterations in collagen fiber morphology or organization. However, the trend toward normalization of myocyte alig nment induced by captopril in non-necrotic zones suggests a possible m echanism for the known beneficial effects of captopril on favorable ve ntricular remodeling. (C) 1997 by Elsevier Science Inc.