Abstract
Myocardial [ATP] falls in the failing heart. One potential compensatory mechanism for maintaining a near normal free energy of ATP hydrolysis (DeltaG approximately (ATP)), despite a fall in [ATP], may be the reduction of myocardial creatine (Cr). To test this, we conducted a longitudinal study using transgenic mice overexpressing cardiac Gsalpha, which slowly developed cardiomyopathy. Myocardial energetics measured using (31)P NMR spectroscopy and isovolumic contractile performance were determined in perfused hearts isolated from 5-, 10-, 17-month-old Gsalpha and age-matched littermate wild type (WT) mice. In young Gsalpha hearts, contractile performance was enhanced with near normal cardiac energetics. With age, as contractile performance progressively decreased in Gsalpha hearts, [ATP] and [PCr] progressively decreased while [Pi] increased only modestly; no changes were observed in WT hearts. Myocardial (but not skeletal) [Cr] in Gsalpha mice decreased, beginning at an early age (1.5 months). Consequently, cytosolic [ADP] and the free energy available from ATP hydrolysis were maintained at normal levels in Gsalpha hearts, despite decreased [ATP]. During increased cardiac work caused by supplying isoproterenol, the relationshi...Continue Reading
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