Importance of metabolic inhibition and cellular pH in mediating preconditioning contractile and metabolic effects in rat hearts

Abstract

The pathophysiological mechanisms by which brief periods of flow interruption before a prolonged ischemic period, ischemic preconditioning (IPC), increase myocardial tolerance to ischemia and improve myocardial function during reperfusion are not completely understood. To test whether short periods of metabolic inhibition in the absence of a flow reduction induce similar protective effects, we studied cardiac function and metabolism using 31P nuclear magnetic resonance spectroscopy in isolated isovolumic rat hearts. Fifteen hearts underwent IPC, consisting of two 5-minute ischemia-reperfusion cycles (IPC group); 18 hearts underwent brief metabolic inhibition by exposure to two 5-minute infusions of 10 mmol/L sodium cyanide (CN group); and 15 hearts served as controls. Subsequently, all hearts were subjected to 30 minutes of total global ischemia at 37°C followed by reperfusion. At the end of the ischemic period, creatine phosphate and ATP levels did not differ among the groups. Cellular pH, however, plateaued at a higher level in the CN group (6.51±0.03) and IPC group (6.12±0.06) than in the control group (5.84±0.01, P