TIME-COURSE OF SPIRAPRIL-INDUCED STRUCTURAL AND FUNCTIONAL-CHANGES AFTER MYOCARDIAL-INFARCTION IN RATS FOLLOWED WITH MAGNETIC-RESONANCE-IMAGING

Structural alterations after myocardial infarction (MI) in rats are us ually examined only after death of the experimental animal. Magnetic r esonance imaging (MRI) allows repeated and noninvasive measurements of important structural [left ventricular (LV) mass, LV wall thickness, LV chamber radius] as well as function [LV end-systolic and LV end-dia stolic volume, stroke volume (SV), ejection fraction (EF)] parameters for a prolonged period. We describe our experience in a series of expe riments in rats. Three weeks after MI, infarct size (IS) was determine d by MRI and the rats were divided into two groups with equal IS. Thre e weeks later, treatment with the angiotensin-converting enzyme (ACE) inhibitor spirapril (10 mg/kg in food) or placebo was started. In both groups, the first MRI scan taken before the treatment showed moderate ly dilated left ventricles and signs of impaired LV function, i.e., an increase in LV end-systolic and end-diastolic volume and decreased EF . After 3-week treatment, no significant differences with respect to h eart structure and function were detected as compared with those of un treated animals. Prolonged treatment for 10 weeks with spirapril resul ted in significant reduction of LV dilatation, LV mass, and LV end-sys tolic and end-diastolic volume, which was accompanied by improved EF. Hemodynamic examinations after treatment for 6 months showed, in contr ast to control animals, no increase in right ventricular systolic pres sure in animals receiving spirapril. Furthermore, histologic examinati on of perfusion-fixed hearts at the end of the study demonstrated more pronounced LV dilatation in control animals, thus confirming the in v ivo MRI data. Delayed treatment with spirapril proved to have benefici al effects on structure and function of infarcted hearts within 10 wee ks. Spirapril limited LV dilatation, reduced LV weight and LV end-syst olic and end-diastolic volumes, and improved EF.