Calcium channel antagonists (CCAs) have been proposed to prevent
cardiac events after
myocardial infarction (MI). However, unwanted effects, such as negative inotropy, limit their use in many cases. The aim of this study was to compare the effects of long-term treatment with the CCAs,
mibefradil,
verapamil, and
amlodipine, administered before and after chronic MI on myocardial remodeling and cardiac function. MI was induced by permanent
ligation of the left coronary artery in male Wistar rats. Infarcted animals were treated with placebo,
mibefradil (10 mg/kg/d po),
verapamil (8 mg/kg bid po), or
amlodipine (4 mg/kg/d po). Treatment was started 7 days before or 3 h after MI induction. Six weeks after MI, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), and cardiac contractility (dP/dt(max)) were measured. Morphometric parameters such as
infarct size (IS), left ventricular dilation (LVD), septal thickness (ST), and cardiac
fibrosis were determined in
picrosirius red-stained hearts. Six weeks after MI, MAP and dP/dt(max) were decreased, whereas LVEDP and HR were increased in placebo-treated controls. The hearts featured an IS of 45%, left ventricular dilation, cardiac
fibrosis, and septal thinning. MAP of all CCA-treated animals was increased, whereas LVEDP was decreased and dP/dt(max) increased 7-day pre- and 3-h post-MI started in
mibefradil- and
amlodipine-treated animals, but not in
verapamil-treated animals. In contrast to
amlodipine treatment, before and after MI started
mibefradil and
verapamil treatment decreased HR. Pretreatment with all CCA reduced IS and increased ST, whereas only
mibefradil and
amlodipine pretreatment prevented LVD and cardiac
fibrosis. After MI started treatment with
mibefradil and
amlodipine reduced IS and cardiac
fibrosis, and increased ST. Long-term treatment with the CCAs
mibefradil,
verapamil, and
amlodipine reduced myocardial remodeling and improved cardiac function in MI-induced
heart failure in rats.