Adaptive changes of pyruvate oxidation in perfused heart during adrenergic stimulation

Pyruvate oxidation was studied in isolated guinea pig hearts perfused under various conditions of work and stimulated by norepinephrine. Hearts metabolized pyruvate alone or in combination with 3-hydroxybutyrate or acetate as substrate. [1-14C]-pyruvate-dependent 14CO2 release into the venous effluent (MVpyr) was, like myocardial oxygen consumption (MVO2), directly related to aortic pressure or filling pressure. At high aortic pressures, ventricular pressure development and not work performance was the major determinant of MVO2 and thus MVpyr. With 1 mM pyruvate as sole substrate, 0.08 microM norepinephrine produced parallel changes in hemodynamic performance, MVO2. MVpyr, and pyruvate dehydrogenase complex (PDC) activity (active form). Similar and dose-dependent effects of norepinephrine were observed during infusion of 5 mM DL-3-hydroxybutyrate as cosubstrate. When 1 mM acetate was applied, MVpyr was also dependent on work performance and norepinephrine stimulation. However, in perfusions with 25 mM potassium chloride, norepinephrine did not enhance hemodynamic function or MVO2 and hence PDC activity and MVpyr. Thus regulation of the PDC in catecholamine-stimulated heart appears to be linked predominantly to myocardial energy demand even when alternative energy-providing substrates are utilized.