Respiratory control in normal and hypertrophic hearts

See article of Bache et al. [1] (pages 616–626) in this issue. In a paper in the current issue of Cardiovascular Research, Bache, Zhang, Murakami, Zhang, Cho, Merkle, Gong, Fraser and Ugurbil [1] look at the proposition that the exaggerated depletion of PCr (phosphocreatine) and accumulation of inorganic phosphate (Pi) that occurs in left ventricular hypertrophy (LVH) is the result of impaired myocyte oxygenation. Using 31P- and 1H-NMR spectroscopy to determine myocardial high energy phosphate (HEP) levels and myoglobin desaturation the authors show convincingly that even at high work loads the exaggerated depletion of PCr and the increase in Pi are not the result of inadequate cellular oxygenation. They also conclude that the greater loss of PCr in the hypertrophic hearts during high work rates is probably caused by alterations in the regulation of myocardial oxidative phosphorylation. Their conclusion of adequate cellular oxygenation would receive support from earlier in situ studies of mitochrondrial function in volume- and pressure-overloaded rat hearts, where the authors [2] reported alterations in mitochondrial function despite adequate cytosol oxygenation. The main energy consuming reactions occur in the cytosol where ATP (adenosine triphosphate) is utilized primarily by the actomyosin ATPase and various ion pumps during contraction and relaxation while resynthesis of ATP occurs within the mitochondria through the process of oxidative phosphorylation. The heart has limited capacity for glycolytic synthesis of ATP and is highly dependent on oxidative phosphorylation, as is evidenced by the fact that mitochondria account for 20–40% of cell volume depending on species. Oxidation of carbohydrates through the tricarboxylic acid cycle (TCA) or fats through the β-oxidation pathway provides intramitochondrial NADH (reduced nicotinamide adenine dinucleotide) and FADH which are the direct source of reducing equivalents (electrons) for the electron transport chain. According to the chemiosmotic hypothesis, the flow of electrons …