Metformin Prevents the Development of Chronic Heart Failure in the SHHF Rat Model

Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investi-gated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was char-acterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodel-ing, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic en