IMPORTANCE OF THE EARLY ALTERATIONS OF ENERGY-METABOLISM IN THE INDUCTION AND THE DISAPPEARANCE OF ISCHEMIC PRECONDITIONING IN THE ISOLATEDRAT-HEART

The kinetics of alterations in high energy phosphates were studied in isolated rat hearts during single and multiple ischemic preconditionin g (IPC) using [P-31]-nuclear magnetic resonance (NMR) spectroscopy. Ao rtically perfused hearts were subjected to a 25 min sustained ischemia and a 30 min reperfusion. The TPC protocols used a basic pattern of 3 min ischemia plus 6 min renew, increasing the reflow period from 6 to 12 min. Efficient IPC was associated during ischemia with a reduction in-ATP degradation, in intracellular acidosis and a maintenance of a residual pool of PCr. Analysis of the IPC phase showed that each short ischemia was followed by a vasodilation (40-50%), accompanied by a cl ear PCr overshoot (115-125%) and a cytosolic P-1 undershoot. Thus, the energy producing reactions were swung out of their initial equilibriu m. The PCr overshoot remained up to the onset of the sustained ischemi a in the efficient protocols, whereas it has practically vanished in t he unefficient ones. In addition, the duration of such a positive imba lance appeared reinforced and prolonged by multiple IPC. It is suggest ed that an IPC cycle induced a time-dependent positive imbalance in th e mitochondrial oxphosphorylative reactions. The benefit for the heart developed only when the prolonged ischemia was imposed under such con ditions, modifying thereby the early dynamics of the energy metabolism processes during the initial phase of the sustained ischemia. (C) 199 6 Academic Press Limited