Early donepezil monotherapy or combination with metoprolol significantly prevents subsequent chronic heart failure in rats with reperfused myocardial infarction

Abstract

Despite the presence of clinical guidelines recommending that β-blocker treatment be initiated early after reperfused myocardial infarction (RMI), acute myocardial infarction remains a leading cause of chronic heart failure (CHF). In this study, we compared the effects of donepezil, metoprolol, and their combination on the progression of cardiac remodeling in rats with RMI. The animals were randomly assigned to untreated (UT), donepezil-treated (DT), metoprolol-treated (MT), and a combination of donepezil and metoprolol (DMT) groups. On day 8 after surgery, compared to the UT, the DT and DMT significantly improved myocardial salvage, owing to the suppression of macrophage infiltration and apoptosis. After the 10-week treatment, the DT and DMT exhibited decreased heart rate, reduced myocardial infarct size, attenuated cardiac dysfunction, and decreased plasma levels of brain natriuretic peptide and catecholamine, thereby preventing subsequent CHF. These results suggest that donepezil monotherapy or combined therapy with β-blocker may be an alternative pharmacotherapy post-RMI.