Fueling normal and diseased hearts: Myocardial bioenergetics

The blood pressure generated by the heart is an essential feature of life; beating ~2-3 billion times during an average lifetime, the heart is a wonder of evolution. The overall contractile performance of the heart depends upon: (1) the delivery of blood containing carbon substrates and oxygen through the coronary circulation to cardiomyocytes; (2) the ability of 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 converted into mechanical energy, which pressurizes and moves blood through the arterial circulation. Importantly, demands placed on the heart are highly dynamic, and, thus, the mechanisms of energy conversion must be tightly regulated to maintain cytosolic and intra-organelle homeostasis. The latter characteristic is crucial if the performances of the contractile apparatus and intracellular organelles are to remain optimal over the broad range of cardiac work states required by a physically active human. Critically, in contrast to skeletal muscles that undergo fatigue and decreased contractile performance after strenuous work, the heart, even at a high rate of myocardial energy expenditure, must not become fatigued as declines in cardiac contractile performances can be life-threatening. This chapter describes the ways in which the chemical energy stored in ingested carbon substrates (primarily glucose and fatty acids) is converted into adenosine triphosphate (ATP) and reviews some of the regulatory systems that integrate the function of these pathways and provide responsiveness to changes in ATP demand in proportion to changes in cardiac workload without destabilizing the intracellular milieu. The generation of toxic by-products of the metabolic processes and the 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.