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The isolated, perfused heart is known to exhibit a linear relation between aortic pressure, coronary flow rate, oxygen consumption and contractile function (rate-pressure product) over a wide range of aortic pressures. Our study sought to determine whether the cytosolic phosphorylation potential [( ATP]/[ADP][Pi]) is the link between mitochondrial respiration and contractile function in this preparation. 31P NMR spectroscopy was used to measure phosphate metabolite levels in isovolumic rat hearts during graded perfusion from 1.6 to 12.8 ml/min/g. It was found that an increase in contractile function paralleled the increase in flow rate, but that marked changes in creatine phosphate, inorganic phosphate and hydrogen ion concentration occurred only at lower flow rates. The cytosolic phosphorylation potential showed a high, positive correlation with contractile function at flow rates below 7.2 ml/min/g, which suggested that mitochondrial respiration was oxygen-limited and that the heart was ischemic. Thus, when oxygen limits myocardial oxidative phosphorylation, cytosolic energy metabolite levels may limit contractile function. At the higher flow rates studied, other metabolic controls may operate to link mitochondrial respiration and workload.

Original publication

DOI

10.1016/s0022-2828(87)80525-4

Type

Journal article

Journal

J Mol Cell Cardiol

Publication Date

12/1987

Volume

19

Pages

1153 - 1160

Keywords

Adenine Nucleotides, Animals, Coronary Circulation, Energy Metabolism, Magnetic Resonance Spectroscopy, Male, Myocardial Contraction, Myocardium, Oxidative Phosphorylation, Oxygen, Perfusion, Phosphocreatine, Rats, Thermodynamics