Maximum oxidative phosphorylation capacity of the mammalian heart

Abstract

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 (MV(O2 mito)) was determined with saturating levels of oxygen, substrates, and cofactors at 37 degrees C. These rates were normalized to cytochrome alpha1 alpha3 (cytochrome oxidase; Cyt a) content. To extrapolate this rate to the intact heart, the Cyt a content of the myocardium (nmol Cyt a/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 O2 x min(-1) x nmol Cyt a(-1) in the dog and pig, respectively. The Cyt a content in the two species was 43.6 +/- 2.4 and 36.6 +/- 3.1 nmol Cyt a/g wet wt, respectively. With these values, the MV(O2 mito) was calculated to be 29.5 (dog) and 24.3 (pig) micromol O2 x min(-1) x 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.

Regulation of oxidative phosphorylation through parallel activation

“…In intact human skeletal muscle the maximal VO 2 recalculated for the mitochondria volume is 2-5(-7) times greater than in isolated mitochondria [47] (see also [48][49][50] and calculations in [13]). It was postulated that the maximal VO 2 in heart [75] and in skeletal muscle in quadrupeds [76] matches well the maximal VO 2 in isolated heart mitochondia and skeletal muscle mitochondria, respectively; however, as it is discussed below, the interpretation of these results is not so strightforward.…”

Stimulatory Effects of Calcium on Respiration and NAD(P)H Synthesis in Intact Rat Heart Mitochondria Utilizing Physiological Substrates Cannot Explain Respiratory Control in Vivo

“…The results plotted in Fig. 7 (A (respiration) and B (redox versus respiration)) show that respiration was stimulated from 0 to 100 nM Ca The effect of Ca 2ϩ on the respiration and redox responses of cardiac mitochondria has been found to be dependent on the substrates used, the species of the animal, and the experiment temperature (5,6,19,21). The cited studies reported that the stimulatory effect of Ca 2ϩ on State 3 mitochondrial respiration with pyruvate/malate was between 20 and 30%; therefore, subsaturating 2-oxoglutarate or saturating glutamate and malate were used as substrates to demonstrate Ca 2ϩ stimulation of mitochondrial State 3 respiration.…”

Excitation-contraction coupling and mitochondrial energetics

“…The main cellular energy consumers are the myosin ATPase of the contractile filaments, the plasmalemmal Na + /K + -ATPase, and the SR Ca 2+ -ATPase [15]. It is assumed that ∼2% of the cellular ATP pool is consumed in each heart beat, and during maximal workload, the whole ATP pool is turned over within a couple of seconds [7,80,139]. The main sites of energy production are the mitochondria, which take up ∼30% of cellular volume [15,222] and are located in close vicinity to the main sites of energy consumption, i. e., the myofilaments, the SR and t-tubules (Figs.…”