Abstract In aerobic tissues, such as cardiac and skeletal muscle, short term increases in energy demand are met primarily by acute regulation of mitochondrial pathways. Chronic increases in time-average metabolic rate of an individual or tissue can lead to modest “physiological adaptations” that may result in increased metabolic capacities and more efficient energy production and utilization. These physiological adaptations differ fundamentally from those which alter metabolic rate acutely. Analysis of the metabolic strategies used by an individual to chronically elevate cardiac metabolic rates may help identify the components of cardiac metabolism which may be constrained or malleable over evolutionary time. While pronounced physiological differences in cardiac energy transduction are apparent across species, the evolutionary origins of such differences are difficult to assess. However, the functional consequences of such differences in homologous tissues across species can be discussed with more certainty. Both chronic hypermetabolic challenges and interspecies comparisons suggest highly oxidative tissues such as heart are restricted to strategies which a) elevate the functional mass b) make more efficient use of intracellular space devoted to mitochondria and c) shift toward more efficient metabolic fuels, primarily fatty acids if oxygen delivery is not a factor.
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