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Restoration of Vagal Tone by Donepezil Markedly Improves Long‐term Survival in Rats with Incurably Severe Heart Failure
Author(s) -
Li Meihua,
Zheng Can,
Kawada Toru,
Inagaki Masashi,
Shishido Toshiaki,
Sato Takayuki,
Sugimachi Masaru
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a801-c
Subject(s) - donepezil , medicine , heart failure , myocardial infarction , cardiology , preload , anesthesia , hemodynamics , dementia , disease
We have demonstrated that chronic electrical vagal nerve stimulation improves long‐term survival of rats with chronic heart failure (CHF) after myocardial infarction (MI), and that this beneficial effect is mainly exerted by acetylcholine through direct actions on cardiomyocytes but not by sympathetic antagonism. 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 if these effects can be reproduced with oral administration of donepezil in rats with severe CHF. Methods: Rats that survived after extensive (52 ± 4%, mean ± SD) myocardial infarction were assigned to donepezil‐treated (DT, 5 mg/kg/day in drinking water) or untreated (UT) groups. Results: Donepezil treatment markedly improved 140‐day survival of CHF rats (27% to 54%, p=0.01; Figure), through the prevention of pumping failure (LV dp/dt max, +18%; Cardiac index, +29%; LVEDP, ‐22%) and cardiac remodeling (cardiac weight; −11%). Conclusion: Pharmaceutical restoration of vagal tone by donepezil markedly improved long‐term survival in rats with extensive MI, suggesting donepezil as a new alternative for CHF therapy.