Metformin Reduces Left Ventricular Eccentric Re-modeling In Experimental volume Overload in the Rat

Left ventricular hypertrophy (LVH) is often associated with a change in myocardial energy substrate preference fatty acids to glucose. A possible anti hypertrophic treatment strategy could aim at stimulating or restoring myocardial energy metabolism. Metformin, an adenosine monophosphate-activated protein kinase (AMPK) used in the management of glucose metabolism in diabetes, is also a fatty acid oxidation stimulator. The of metformin on the development of eccentric LVH and ventricular function in chronic left ventricular (LV) overload (VO) is unknown. This study was designed to study this question in a VO rat model caused by aortic valve regurgitation (AR). Male Wistar rats were divided in four groups (13-15 animals / group): Shams (S) treated or not (C) with metformin (M; 100 mg/kg/d PO) and severe ARreceiving or not metformin. Treatment was one week before surgery and the animals were sacrificed 9 weeks later. As expected AR rats developed eccentric LVH during the course of the protocol. Metformin treatment did not influence the total heart weight. , LV remodeling associated with the severe VO was severe in ARM than in ARC. Fractional shortening, a of systolic function, was significantly higher in ARM compared to ARC group. Metformin also increased the of enzymes associated with fatty acid oxidation while inhibiting phosphofructokinase, a glycolytic enzyme. A 2 month treatment with metformin reduced LV eccentric remodeling associated with severe VO and helped maintain better systolic function.