Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice.
J Card Fail
; 15(9): 805-11, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19879468
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 ANDRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Doença de Alzheimer
/
Insuficiência Cardíaca
/
Indanos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Card Fail
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão