Importance of the early alterations of energy metabolism in the induction and the disappearance of ischemic preconditioning in the isolated rat heart.

The kinetics of alterations in high energy phosphates were studied in isolated rat hearts during single and multiple ischemic preconditioning (IPC) using [31P]-nuclear magnetic resonance (NMR) spectroscopy. Aortically perfused hearts were subjected to a 25 min sustained ischemia and a 30 min reperfusion. The IPC protocols used a basic pattern of 3 min ischemia plus 6 min reflow, 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 clear PCr overshoot (115-125%) and a cytosolic Pi undershoot. Thus, the energy producing reactions were swung out of their initial equilibrium. The PCr overshoot remained up to the onset of the sustained ischemia in the efficient protocols, whereas it has practically vanished in the unefficient ones. In addition, the duration of such a positive imbalance appeared reinforced and prolonged by multiple IPC. It is suggested that an IPC cycle induced a time-dependent positive imbalance in the mitochondrial oxphosphorylative reactions. The benefit for the heart developed only when the prolonged ischemia was imposed under such conditions, modifying thereby the early dynamics of the energy metabolism processes during the initial phase of the sustained ischemia.