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 ischemic preconditioning, the effects of a compound, (4-isopropyl-3-methylsulphonylbenzoyl)guanidine hydrochloride (HOE 642), known to inhibit the Na+/H+ exchange in rat cardiomyocytes. In rat isolated hearts, perfused on a Langendorff apparatus with Krebs-Henseleit carbonate buffer, the action potentials and the contractile function were measured during a 25-min period of global low-flow ischemia (coronary flow, 0.3 mL.min-1) followed by a 30-min reperfusion. In hearts previously preconditioned, two intermittent periods of total ischemia for 5 min each, separated by 5 min reflow, were performed before low-flow ischemia. Treated hearts received HOE 642 (3.0 x 10(-8) mol.min-1) exclusively during low-flow ischemia. Treatment with HOE 642 during low-flow ischemia improves cardiac performance and lowers the rise in diastolic tension during reperfusion. Concomitantly HOE 642 shortens the action potential, and has striking effects on ventricular arrhythmias during reperfusion 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 preconditioning protocol, but a lengthening in action potential was observed and ventricular arrhythmias were mostly affected. Preconditioned hearts demonstrated marked glycogen depletion compared with controls. These results support the hypothesis that preconditioning could decrease glycogenolysis and therefore subsequently limit acidification during low-flow ischemia.
Perchenet
L
L
Laboratoire de neurophysiologie, CNRS EREA 120, Université d'Angers, France.
Rochetaing
A
A
Gallois
Y
Y
Kreher
P
P
D000200:Action Potentials; D000818:Animals; D004594:Electrophysiology; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; D006003:Glycogen