Abstract 14245: Central Administration of Donepezil Prevents Progression of Cardiac Remodeling in Rats After Extensive Myocardial Infarction
Introduction: Previous studies have proved that oral administration of donepezil improves prognosis in chronic heart failure (CHF) rats, but its mechanisms remains unclear. As a centrally acting reversible acetylcholinesterase inhibitor, donepezil may exert the beneficial effects through central pathway. The present study aimed to verify whether central infusion of donepezil effectively prevent cardiac remodeling in CHF rats after extensive myocardial infarction (MI).
Methods: Rats survived for one week after MI were implanted with a blood pressure transmitter and a micro-infusion pump which connected with a cerebroventricular cannula and. Animals were randomly assigned to central saline (CST, n=14) or central donepezil (CDT, n=13) infusion groups. Donepezil was administered at a dosage of 0.1 mg/kg/day for 6 weeks.
Results: Although there was no significant difference in the MI size between the two groups, CDT significantly decreased the heart rate (300 ± 12 vs. 341 ± 10 bpm, P < 0.05) and prevented cardiac dysfunction [Left ventricular (LV) dp/dt max, +16%; Cardiac index, +25%; LV end-diastolic pressure (LVEDP), -5mmHg; Right atrial pressure (RAP), -3mmHg] than CST group (Table). Improvement of these hemodynamic parameters was accompanied by significant decreases in biventricular weight and cardiac fibrosis. Plasma levels of B-type natriuretic peptide (BNP), arginine vasopressin (AVP) and norepinephrine (NE) were significantly lower in CDT than CST group.
Conclusion: Central pathway plays an important role in the donepezil treatment which prevents the progression of cardiac remodeling and dysfunction in CHF rats.
- © 2013 by American Heart Association, Inc.