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

• DOI: 10.1042/cs20100527
• Publication Date: 2011-02-17T14:34:10Z
• Authors: Jan Benes; Ludmila Kazdova; Zdenek Drahota; Josef Houstek; Dasa Medrikova; Jan Kopecky; Nikola Kovarova; Marek Vrbacky; David Sedmera; Hynek Strnad; Michal Kolar; Jiri Petrak; Oldrich Benada; Petra Skaroupkova; Ludek Cervenka; Vojtech Melenovsky
• Keywords: Carbohydrate Metabolism; Preload

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of use improves the course remains unknown. The antihyperglycaemic drug MET (metformin) affects metabolism, and its might be improved outcome in diabetic HF. aim present study was to examine whether would improve cardiac function survival also non-diabetic Volume-overload induced male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized placebo/MET (300 mg·kg(-1) body weight·day(-1), 0.5% food) groups underwent assessment cardiovascular mitochondrial functions (n=6-12/group) advanced stage (week 21). A separate cohort served for analysis (n=10-90/group). group had marked hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) lung weight confirming decompensated HF, circulating NEFAs (non-esterified 'free' fatty acids), intra-abdominal fat depletion, lower glycogen synthesis skeletal muscle (diaphragm), myocardial triacylglycerol (triglyceride) content attenuated (14)C-glucose (14)C-palmitate oxidation, but preserved respiratory function, glucose tolerance insulin sensitivity. therapy normalized serum NEFAs, decreased palmitate it no effect on gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, respiration, morphology, long-term survival, despite reaching therapeutic levels (2.2±0.7 μg/ml). In conclusion, MET-induced enhancement acid oxidation a neutral survival. Recently reported cardioprotective effects may not universal all forms require activation or depletion. No increase mortality supports safe