High-energy phosphates metabolism and recovery in reperfused ischaemic hearts.

Abstract

The aim of this study was to assess how coronary flow, oxygen supply and energy demand affect myocardial ATP, phosphocreatine and their metabolites during oxygen shortage and recovery. Isolated rat hearts were exposed for 20 min to either low-flow ischaemia or hypoxaemia at the same oxygen supply, followed by return to baseline conditions (20 min). Seventy-three hearts were divided into four groups: ischaemic or hypoxaemic, spontaneously beating or paced to increase energy demand. During O2 shortage, myocardial performance was less in ischaemic, spontaneously beating hearts (SpIs), than in the other groups (14 +/- 1% of baseline vs. 25-48%). Consequently, the tissue levels of ATP, total adenylates and phosphocreatine were maintained in SpIs, in contrast to marked decreases in the other groups. Upon reflow, the recovery of performance and of myocardial ATP was 94 +/- 5% in SpIs (P = NS vs. baseline) compared with 64-85% (P < 0.05 vs. baseline) in the other groups. The degree of recovery was positively related to the ischaemic contents of ATP (P = 0.03) and adenylates (P = 0.001), but not to that of phosphocreatine (P = NS). The maintenance of the ATP pool under low oxygen supply conditions is essential for good recovery. The most important factors that determine the ATP pool size are the energy demand, which increases the formation of diffusible ATP catabolites, and the coronary flow, which removes these catabolites, rather than the oxygen supply per se.