ATP and Cytochrome C Oxidase in the Failing Human Heart

Publisher Summary Adenosine triphosphate (ATP) is the primary source of chemical energy for cardiac Excitation–contraction coupling. There are metabolic abnormalities in the failing human heart that can have a negative impact on ventricular function. Total creatine, adenine, and pyridine nucleotide concentrations are significantly lower, on the average, in failing, as compared with normal, human hearts. Depressed ATP is strongly associated with diastolic dysfunction, a relationship most apparent in patients with pure restrictive cardiomyopathies. An ischemic basis for altered metabolite levels, even in the absence of significant coronary artery disease, is suggested by the increased amount of superoxide dismutase found in end-stage failing hearts. The increase in superoxide dismutase, a copper-containing enzyme, is accompanied by decreases in the nuclear-encoded subunits of cytochrome c oxidase-a phenomenon similar to that observed in severe dietary copper deficiency.