Redox Manipulation of Free Cardiac Adenylates and Purine Nucleoside Release

Abstract

The thermodynamic equilibrium relations between free adenylates and redox state in the cytosol were reviewed as applicable to perfused heart. Studies with isolated working guinea-pig hearts examined cytosolic redox state, phosphorylation potential, and the free concentration of AMP ([AMP]) in relation to the coronary venous output of adenylate catabolites. Excess pyruvate (20 mM), relative to 20 mM lactate, produced increases in the phosphorylation potential and total cardiac AMP content, but inorganic phosphate content, [ADP], [AMP], and purine nucleoside release were decreased. Conversely, excess lactate induced the releases of inosine and large amounts of xanthine, the reduced precursor of uric acid. When 15 mM glucose was the sole substrate, lactate output and adenosine plus inosine release changed concordantly during adrenergic stimulation. During low-flow ischemia with adrenergic stimulation, output of purines showed a large but transient increase, was mainly (67% – 87%) in the form of adenosine plus inosine, and was attenuated by cytosolic oxidation due to intracoronary administration of 5 mM pyruvate. Uric acid output accounted for 40% – 50% of total purine release during normoxia, but for not more than 10% during early ischemia.KeywordsUric AcidCreatine KinasePurine NucleosidePurine ReleaseExcess PyruvateThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.