Purine release from isolated rat heart: a new approach to the study of energy metabolism

The rate of release of purines (adenosine, inosine, hypoxanthine, xanthine and uric acid) from isolated working rat hearts was measured and compared to tissue concentrations of high energy phosphate compounds. Hearts were subjected to different workloads, and perfusions were performed: with normal oxygen supply (group 1); with the addition of insulin to the standard perfusion buffer, which contained glucose as energy source (group 2); in hypoxic conditions (group 3). In each group purine release increased (P less than 0.01) at higher workload and was closely related to indices of mechanical performance such as cardiac output or minute work (r = 0.902 and 0.858 in group 1, r = 0.902 and 0.851 in group 2, r = 0.851 and 0.881 in group 3, P less than 0.001 in each case). Work had no effect on adenine nucleotides but produced a significant (P less than 0.01) reduction in phosphocreatine/creatine ratio. The comparison of different groups showed that at any level of heart performance purine release was higher (P less than 0.001) in group 3 vs. group 1, and lower (P less than 0.001) in group 2 vs. group 1. High energy phosphates were reduced in group 3 vs. group 1 but were unchanged in group 2 vs. group 1. We conclude that in the isolated heart purine release is directly related to the rate of energy consumption, and inversely related to the rate of energy production. Purine release provides a sensitive method to evaluate myocardial energy metabolism, which is more sensitive than measurement of high energy phosphates.