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 usually examined only after death of the experimental animal. Magnetic resonance 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-diastolic volume, stroke volume (SV), ejection fraction (EF)] parameters for a prolonged period. We describe our experience in a series of experiments in rats. Three weeks after MI, infarct size (IS) was determined by MRI and the rats were divided into two groups with equal IS. Three 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 moderately 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 heart structure and function were detected as compared with those of untreated animals. Prolonged treatment for 10 weeks with spirapril resulted in significant reduction of LV dilatation, LV mass, and LV end-systolic and end-diastolic volume, which was accompanied by improved EF. Hemodynamic examinations after treatment for 6 months showed, in contrast to control animals, no increase in right ventricular systolic pressure in animals receiving spirapril. Furthermore, histologic examination of perfusion-fixed hearts at the end of the study demonstrated more pronounced LV dilatation in control animals, thus confirming the in vivo MRI data. Delayed treatment with spirapril proved to have beneficial effects on structure and function of infarcted hearts within 10 weeks. Spirapril limited LV dilatation, reduced LV weight and LV end-systolic and end-diastolic volumes, and improved EF.
Zierhut
W
W
Sandoz Pharma Preclinical Research, Basel, Switzerland.
Rudin
M
M
Robertson
E
E
Zerwes
H G
HG
Novosel
D
D
Evenou
J P
JP
Stirnimann
R
R
Hof
R P
RP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004656:Enalapril / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology* / Q000503:physiopathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; C052555:spirapril; D007703:Peptidyl-Dipeptidase A