Anti-Alzheimer's Drug, Donepezil, Markedly Improves Long-Term Survival After Chronic Heart Failure in Mice

Takemi Handa, Rajesh G. Katare, Yoshihiko Kakinuma, Mikihiko Arikawa, Motonori Ando, Shiro Sasaguri, Fumiyasu Yamasaki, Takayuki Sato

Research output: Contribution to journalArticle

42 Citations (Scopus)

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 mg·kg-1·day-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.

Original languageEnglish
Pages (from-to)805-811
Number of pages7
JournalJournal of Cardiac Failure
Volume15
Issue number9
DOIs
Publication statusPublished - Nov 1 2009
Externally publishedYes

Keywords

  • Acetylcholine
  • heart failure
  • survival
  • vagus nerve

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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