Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice.
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.


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.
Handa
Takemi
T
Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan. takemi@mpd.biglobe.ne.jp
Katare
Rajesh G
RG
Kakinuma
Yoshihiko
Y
Arikawa
Mikihiko
M
Ando
Motonori
M
Sasaguri
Shiro
S
Yamasaki
Fumiyasu
F
Sato
Takayuki
T
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D004195:Disease Models, Animal; D000077265:Donepezil; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000627:therapeutic use*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome
D007189:Indans; D010880:Piperidines; D000077265:Donepezil