Electrocardiographic Changes and Mortality Due to Myocardial Infarction in Rats With or Without Imidapril Treatment

Abstract

BACKGROUND: Various angiotensin-converting enzyme inhibitors are known to improve heart function and prolong survival in patients and animals after myocardial infarction. Because myocardial infarction is known to induce arrhythmias, this study tested the hypothesis that early treatment with the angiotensin converting enzyme inhibitor imidapril reduces mortality during acute myocardial infarction because of protective effects against arrhythmogenesis. METHODS AND RESULTS: Rats were randomly divided into four groups: sham control, myocardial infarction, sham plus imidapril, and myocardial infarction plus imidapril. Myocardial infarction was produced by ligation of the left anterior descending coronary artery. Treated rats received imidapril (1 mg/kg/day) through a gastric tube beginning 1 hour after coronary occlusion; control rats received tap water. Electrocardiogram (ECGs) were recorded 1, 3, 7, and 21 days postocclusion. Infarct size and scar weight were determined at 21 days in the myocardial infarction groups with and without imidapril treatment. ECGs of untreated rats showed ST-segment changes, abnormal Q waves, premature ventricular complexes, and QT(c) prolongation 1-21 days after coronary occlusion. Total mortality in 21 days averaged 35% in untreated rats; mortality within 48 hours was 30%. On the other hand, imidapril-treated rats showed fewer ST-segment changes, fewer abnormal Q waves, and a decreased incidence of premature ventricular complexes after coronary occlusion; the ST-segment and QT(c) interval returned to basal values within 1 week after occlusion. Imidapril treatment did not affect the ECG pattern in sham-treated control animals. Total mortality in the imidapril-treated group in 21 days after infarction was 22.5%; mortality within 48 hours was 20% (P <.05 compared with the untreated infarction group). Infarct size and scar weight caused by coronary occlusion did not differ in the untreated and imidapril-treated groups. CONCLUSIONS: Early treatment with imidapril markedly decreases mortality in rats after acute myocardial infarction. The lower mortality is not associated with a decrease in infarct size but is consistent with a protective effect of the drug against arrhythmogenesis.

Blockade of 5-HT2A Receptors by Sarpogrelate Protects the Heart Against Myocardial Infarction in Rats

“…Three-lead (limb leads I, II, and III) electrocardiograms (ECGs) were recorded in experimental rats on days 1, 3, 7, and 21 after coronary occlusion (20). The control values were measured in all rats before occluding the coronary artery.…”

Imidapril treatment improves the attenuated inotropic and intracellular calcium responses to ATP in heart failure due to myocardial infarction

“…The selection of imidapril for this study was mainly due to the fact that this long‐acting ACE inhibitor has been reported to reduce mortality due to coronary artery disease in mice to a greater extent than other ACE inhibitors (Ogiku et al ., 1994). In addition, imidapril has been shown to reduce mortality and prevent subcellular remodeling in the MI rat model of CHF (Ren et al ., 1998; Tappia et al ., 1999; Wang et al ., 2002; 2003). Some experiments were also carried out to test if another ACE inhibitor, enalapril (Fujii et al ., 2002), and an AT 1 R blocker, losartan (Ruzicka et al ., 1999), produce effects similar to those seen with imidapril.…”

Attenuation of changes in Gi‐proteins and adenylyl cyclase in heart failure by an ACE inhibitor, imidapril

“…Since renin-angiotensin system (RAS) is known to play an important role in maintaining cardiovascular homeostasis and is considered to be involved in the pathophysiology of myocardial infarction (MI) [17], extensive efforts have been made to improve heart function in the infarcted animals with various RAS inhibitors. Treatment of rats with different angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor (AT1R) antagonists has been shown to prevent ventricular remodelling, improve heart function, change hormone profile and reduce mortality in the infarcted animals [18][19][20][21][22]. Although the cellular and molecular mechanisms by which these drugs improve cardiac function in heart failure have not yet been clearly defined, Shao et al [23] have demonstrated the effect of ACE inhibition on sarcoplasmic reticular gene expression whereas Wang et al [24] demonstrated that the beneficial effects on the failing heart are associated with prevention of changes in myosin heavy chain isozyme protein contents and gene expression.…”