Biochemical and mechanical correlates at peak systole in myopathic Syrian Hamster

Abstract

SummaryThe following studies were carried out to determine the phosphorylation potential of the myopathic Syrian Hamster hearts and whether a decrease in the free energy of ATP hydrolysis and/or shift in isomyosins was responsible for decreased cardiac performance. Hamster hearts were perfused under maximally stressed working conditions, i.e., a workload of 110 mmHg, high calcium concentrations in the perfusate (3.5 mM) and 10−8 M isoproterenol. Mechanical parameters indicated contractility had fallen 50 % in Syrian Hamster hearts under these conditions. Using a specially designed stimulator-triggered freeze-clamp, hearts were terminated at peak systole and tissue content of ATP, ADP, phosphocreatine, creatine, and inorganic phosphate analyzed. Cytosolic concentrations of metabolites were calculated as described by Kammermeier utilizing published data on tissue compartmentation (1, 2). A reduction in contractile performance of the Syrian Hamster hearts not only correlated with a shift in isomyosins but also with a decrease in free energy of ATP hydrolysis from 51.08 kJ/mole in control hearts at peak systole and 45.9 kJ/mole in myopathie hearts at peak systole. These values assume ADP generated from ATP hydrolysis remained free in the cytosol during systole. The low value in myopathie hearts was due to the decrease in ATP and the increase in inorganic phosphate. The reduction in free energy of ATP hydrolysis occurring in Syrian Hamster hearts was sufficient to cause a decrease in contractility: thus a shift in isomyosins, and the cAMP and ATP deficiency appear to be at least partially responsible for a combined coordinate decrease in cardiac performance in the Syrian Hamster.