Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure

Yin M, van der Horst IC, van Melle JP, Qian C, van Gilst WH, Sillje HH, de Boer RA. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol 301: H459-H468, 2011. First published May 13, 2011; doi:10.1152/ajpheart.00054.2011.-Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg.kg(-1).day(-1)). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 +/- 3.2 vs. 38.0 +/- 2.2%, P <0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 +/- 0.4 vs. 7.6 +/- 0.6 mm, P <0.05) and preservation of left ventricular ejection fraction (65.8 +/- 3.7% vs. 48.6 +/- 5.6%, P <0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P