The Molecular Energetics of the Failing Heart from Animal Models―Small Animal Models

Abstract

Small animal models of heart failure have been widely used. Availability of transgenic mice with perturbations of the molecular pathways known to be altered in heart failure will substantially increase the number of small animal models for heart failure research. This chapter summarizes the alterations in myocardial energetics observed in failing hearts of small animal models using the combined tools of 31P NMR spectroscopy and biochemical assays. These include: early depletion of total creatine and phosphocreatine followed by decreased creatine kinase activity; both contribute to decreased capacity and velocity of the creatine kinase reaction resulting in decreased energy reserve during the development of heart failure; decreased ATP content at end-stage failing hearts; and a switch in substrate utilization with increased preference for glucose in hypertrophied and failing hearts. Evidence presented here suggest that these abnormalities contribute to failure to recruit contractile reserve, increased susceptibility for diastolic dysfunction and impaired calcium homeostasis in hypertrophied and failing hearts.