Maximum oxidative phosphorylation capacity of the mammalian heart

It is difficult to estimate the maximum in vivo aerobic ATP production rate of the intact heart independent of limitations imposed by blood flow, oxygen delivery, and maximum mechanical power. This value is critical for establishing the kinetic parameters that control oxidative phosphorylation, as well as for providing insights into the limits of myocardial performance. In this study, the maximum ADP-P-i-driven heart mitochondrial respiratory rate (MVo(2mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha(1) alpha(3) (cytochrome oxidase; Cyt alpha) content. To extrapolate this rate to the intact heart, the Cyt alpha content of the myocardium (nmol Cyt alpha/g wet wt myocardium) was determined in the same hearts. The maximum ADP-P-i-driven mitochondrial respiratory rates were 676 +/- 31 and 665 +/- 65 nmol O-2 . min(-1). nmol Cyt alpha(-1) in the dog and pig, respectively. The Cyt alpha content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt alpha/g wet wt, respectively. With these values, the MVo(2mito) was calculated to be 29.5 (dog) and 24.3 (pig) mu mol O-2 . min(-1). g wet wt myocardium(-1). Comparison with in vivo studies shows that the exercising heart can utilize 80-90% of its maximum oxidative capacity, implying there is little aerobic ATP production reserve in the mammalian heart.