Fueling normal and diseased hearts: Myocardial bioenergetics

Cardiac contractile performance depends upon: (1) the delivery of carbon substrates and oxygen present in the blood to the cardiac extracellular space (via the coronary circulation), (2) the ability of the cardiomyocytes to efficiently extract these substrates from the extracellular space, and (3) the pathways via which the chemical energy stored within the carbon substrates is transferred to adenosine triphosphate (ATP), an energy storage molecule that can be directly utilized by most chemical energy driven processes. Importantly, ATP synthetic capacity must be sufficient to support a wide range of energy demands with high rates of ATP generation and must not be associated with destabilization of cytosolic and intra-organelle chemical milieus. The latter characteristic is crucial if the performance of the contractile apparatus and intracellular organelles is to remain optimal over the broad range of cardiac work states required by a physically active organism. Hence, even a high rate of myocardial energy expenditure must not induce the fatigue that is known to develop in heavily working skeletal muscle. This chapter describes the ways in which the chemical energy stored in ingested carbon substrates (glucose, fatty acids, and, to a modest extent, proteins) is transferred to ATP and reviews some of the regulatory systems which integrate the function of these pathways and make them responsive to changes in ATP demand without destabilizing the intracellular chemical milieu. The generation of toxic by-products of the metabolic processes and mechanisms that limit their adverse effects are also reviewed. Last of all, the effects of several physiological states and diseases on these processes are briefly discussed, and the concept that the diseased heart may be energy limited is presented.