Title : Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice - Handa_2009_J.Card.Fail_15_805 |
Author(s) : Handa T , Katare RG , Kakinuma Y , Arikawa M , Ando M , Sasaguri S , Yamasaki F , Sato T |
Ref : J Card Fail , 15 :805 , 2009 |
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. |
PubMedSearch : Handa_2009_J.Card.Fail_15_805 |
PubMedID: 19879468 |
Handa T, Katare RG, Kakinuma Y, Arikawa M, Ando M, Sasaguri S, Yamasaki F, Sato T (2009)
Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice
J Card Fail
15 :805
Handa T, Katare RG, Kakinuma Y, Arikawa M, Ando M, Sasaguri S, Yamasaki F, Sato T (2009)
J Card Fail
15 :805