Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice. Journal of cardiac failure [J Card Fail] Journal article | | Title | Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice. | | Author(s) | Handa T, Katare RG, Kakinuma Y, Arikawa M, Ando M, Sasaguri S, Yamasaki F, Sato T | | Institution | Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan. takemi@mpd.biglobe.ne.jp | | Source | J Card Fail 2009 Nov; 15(9):805-11. | | Abstract | BACKGROUND: We previously reported that chronic vagal nerve stimulation markedly improved long-term survival after chronic heart failure (CHF) in rats through cardioprotective effects of acetylcholine, independent of the heart rate-slowing mechanism. However, such an approach is invasive and its safety is unknown in clinical settings. To develop an alternative therapy with a clinically available drug, we examined the chronic effect of oral donepezil, an acetylcholinesterase inhibitor against Alzheimer's disease, on cardiac remodeling and survival with a murine model of volume-overloaded CHF.
METHODS AND RESULTS: Four weeks after surgery of aortocaval shunt, CHF mice were randomized into untreated and donepezil-treated groups. Donepezil was orally given at a dosage of 5 mgxkg(-1)xday(-1). After 4 weeks of treatment, we evaluated in situ left ventricular (LV) pressure, ex vivo LV pressure-volume relationships, and LV expression of brain natriuretic peptides (BNP). We also observed survival for 50 days. When compared with the untreated group, the donepezil-treated group had significantly low LV end-diastolic pressure, high LV contractility, and low LV expression of BNP. Donepezil significantly reduced the heart weight and markedly improved the survival rate during the 50-day treatment period (54% versus 81%, P < .05).
CONCLUSIONS: Oral donepezil improves survival of CHF mice through prevention of pumping failure and cardiac remodeling. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19879468 |
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