ELECTROPHYSIOLOGICAL APPROACH OF THE ROLE OF NA+ H+ EXCHANGE IN LOW-FLOW GLOBAL-ISCHEMIA AND IN ISCHEMIC PRECONDITIONING/

We investigated, at first in low-flow global ischemia and then with is chemic preconditioning, the effects of a compound, (4-isopropyl-3-meth ylsulphonylbenzoyl)guanidine hydrochloride(HOE 642), known to inhibit the Na+/H+ exchange in rat cardiomyocytes. In rat isolated hearts, per fused on a Langendorff apparatus with Krebs-Henseleit carbonate buffer . the action potentials and the contractile function were measured dur ing a 25-min period of global low-flow ischemia (coronary flow, 0.3 mL .min(-1)) followed by a 30-min reperfusion. Ln hearts previously preco nditioned, two intermittent periods of total ischemia for 5 min each, separated by 5 min reflow, were performed before low-flow ischemia. Tr eated hearts received HOE 642 (3.0 x 10(-8) mol.min(-1)) exclusively d uring low-flow ischemia, Treatment with HOE 642 during low-flow ischem ia improves cardiac performance and lowers the rise in diastolic tensi on during reperfusion. Concomitantly HOE 642 shortens the action poten tial, and has striking effects on ventricular arrhythmias during reper fusion as well. These results support the concept that Na+/H+ exchange activation is a contributing factor to low-flow ischemia-reperfusion injuries, HOE 642 exhibited minor effects when combined with the preco nditioning protocol, but a lengthening in action potential was observe d and ventricular arrhythmias were mostly affected. Preconditioned hea rts demonstrated marked glycogen depletion compared with controls. The se results support the hypothesis that preconditioning could decrease glycogenolysis and therefore subsequently limit acidification during l ow-flow ischemia.