Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats

0366961 - FGÚ 2012 RIV GB eng J - Journal Article
Beneš, J. - Kazdová, L. - Drahota, Zdeněk - Houštěk, Josef - Medříková, Daša - Kopecký, Jan - Kovářová, Nikola - Vrbacký, Marek - Sedmera, David - Strnad, Hynek - Kolář, Michal - Petrák, J. - Benada, Oldřich - Škaroupková, P. - Červenka, L. - Melenovský, V.
Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats.
Clinical science. Roč. 121, č. 1 (2011), s. 29-41. ISSN 0143-5221. E-ISSN 1470-8736
R&D Projects: GA MŠMT(CZ) 1M0510; GA MZd(CZ) NS9757; GA MŠMT(CZ) 1M0520
Grant - others:GA MZd(CZ) NS10497; GA ČR(CZ) GA305/09/1390
Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50520514; CEZ:AV0Z50200510
Keywords : AMP-activated protein kinase * energy metabolism * heart failure * metformin * survival * volume overload
Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery
Impact factor: 4.317, year: 2011

The present study examined whether metformin would improve cardiac function and survival also in non-diabetic heart failure of male Wistar rats. Metformin therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels in rats with creating aortocaval fistula. In conclusion, metformin-induced enhancement of myocardial fatty acid oxidation had a neutral effect on cardiac function and survival. Reported cardioprotective effects of metformin may not be universal to all forms of heart failure and may require AMPK activation or ATP depletion. No increase in mortality on metformin supports its safe use in diabetic heart failure
Permanent Link: http://hdl.handle.net/11104/0201772