Abstract 1416: Progression of Ventricular Dysfunction after Myocardial Infarction is Prevented by Anti-Alzheimer’s Disease Drug, Donepezil
Introduction: We have previously demonstrated that the vagal nerve stimulation improved survival of murines with both acute and chronic heart failure through release of the neurotransmitter acetylcholine. Recently donepezil (Aricept), an acetylcholinesterase inhibitor, was also found to improve survival rate in rats with chronic heart failure (CHF). However the protective effects of donepezil against cardiac dysfunction have not yet been elucidated. In this study, we investigated whether donepezil prevents progression of left ventricular (LV) dysfunction in ischemic CHF rats.
Methods: Myocardial infarction was constructed by left coronary artery occlusion. The survived rats were thereafter divided into sham, untreated (control) and donepezil-treated (Dpz, 5 mg/kg/day) groups. Six weeks after surgery, LV pressure-volume relationships were determined in Langendorff perfused heart preparation.
Results: Compared to the sham group (Ees=1.03 mmHg/μl, ESV=60 μl estimated from linear regression analysis at ESP=100 mmHg), the control group showed severe depression of LV function (Ees=0.23 mmHg/μl, ESV=320 μl). Donepezil-treated group, to the contrary, exhibited significant improvement of LV contractility (Ees=0.36 mmHg/μl, ESV=210 μl) even though there were no significant differences in curve shapes of end diastolic pressure-volume relationships and values of heart/body weight ratio between control and donepezil-treated groups.
Conclusions: The present results showed that donepezil has a preventive effect on LV dysfunction of ischemic failing hearts, suggesting that donepezil can be a new potential candidate for a clinically useful drug for CHF therapy.