Computer simulation of metabolism in pyruvate-perfused rat heart. V. Physiological implications.

The results of a simulation of metabolism in the pyruvate-perfused rat heart subjected to a sudden increase in work load are interpreted to provide a coherent explanation for the observed physiology. Respiration is most closely correlated with the mitochondrial phosphate potential, calculated from the MgATP and MgADP levels. No correlation between respiration and the pH gradient across the mitochondrial membrane was found. The transient falls in pH in the cytosol and perhaps the mitochondria are due largely to carbonic and lactic acidosis and appear to be only weakly coupled. The heart maintains a high ATP level during the transition to increased work by utilizing its energy reserves in order of decreasing availability in response to physiological signals mediated by Mg2+, Ca2+, and cAMP.