Myocardial ATP synthesis and mechanical function following oxygen deficiency.

Abstract

The relationship between oxygen deficiency-reduced high energy phosphate levels and their resynthesis upon return to aerobic conditions was investigated in the isolated perfused rat heart. Any net adenosine triphosphate (ATP) hydrolysis during anoxia tended to impair ATP resynthesis with subsequent aerobic perfusion. Thirty minutes of ischemia reduced myocardial ATP 50%, and with restoration of aerobic conditions ATP increased to only 60% of control levels. The major source of postischemic and postanoxic ATP was adenosine 5'-monophosphate and adenosine 5'-disphosphate. Loss of purine base from oxygen-deficient cells limited restoration of ATP. The inclusion of adenosine, ATP, or creatine phosphate (CP) in the perfusate did not enhance postischemic tissue adenine-nucleotide concentrations. Postischemic and postanoxic CP concentrations returned to control values and were independent of ischemic and anoxic ATP and CP concentrations. Complete resynthesis of CP suggests that cellular energy-producing pathways were functional. Ventricular performance was directly related to tissue ATP concentration in aerobic control, postischemic, and postanoxic hearts. Thus, loss of adenine nucleotides during oxygen deficiency may impair subsequent aerobic synthesis of ATP and mechanical function.