| Summary: | Heart failure is a devastating disease which despite significant advances in therapy over the
past two decades still results in a poor prognosis. Metabolic dysregulation is associated with
heart failure; however, it remains unclear whether isoproterenol exerts deleterious effects
through altered metabolic regulation. Whether metformin, a metabolic modulator, prevents
isoproterenol-induced heart failure is unknown. The aim of this study was to determine
whether metformin prevents functional and metabolic changes seen in the isoproterenol model
of heart failure. Male Sprague-Dawley rats were administered isoproterenol and metformin
for seven months. Thereafter, cardiac dimensions, metabolic gene expression and myocardial
structural changes were assessed. Chronic administration of isoproterenol induced left
ventricular dilatation and pump dysfunction and mitochondrial structural derangement. No
changes were seen in metabolic gene expression. However, co-administration of metformin
prevented isoproterenol-induced heart failure and retained mitochondrial structural
arrangement. Therefore, cardiac dilatation and pump dysfunction induced by chronic
administration of isoproterenol can be prevented by co-administering metformin.
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