Substrate dependence of metabolic state and coronary flow in perfused rat heart

The effect of substrate source on the regulation of energy metabolism and coronary flow was studied in isolated perfused rat hearts. Compared with glucose-perfused hearts, those perfused at the same work load with palmitate or acetate demonstrated increases (P less than 0.01) in O2 consumption of 16 and 18%, respectively, and increases (P less than 0.01) in coronary flow of 30 and 32%, respectively. Parallel substrate-related changes occurred in the levels of high-energy phosphate compounds: tissue creatine, ADP free, and inorganic phosphate (Pi) were significantly decreased, leading to increases (P less than 0.01) in [creatine phosphate]/[creatine] and [ATP]free/[ADP]free[Pi]. These changes were accompanied by increased reduction of intramitochondrial pyridine nucleotides. Omitting orthophosphate from perfusate lowered intracellular Pi and modified cardiac function, but substrate-related differences were similar to those in Pi containing media. Differences in intracellular pH among substrates were observed, which may contribute in some instances to differences in energy metabolism and coronary flow. When work load was altered in glucose- and acetate-perfused hearts, both O2 consumption and coronary flow were linearly related to cytosolic [ATP]free/[ADP]free[Pi], and slopes of regression lines were similar for both substrates. These correlations support the view that [ATP]free/[ADP]free[Pi] is a major determinant of O2 consumption by cardiac cells and of coronary flow.