Faculty Collaboration Database

Inhibition of the Na(+)/H(+) exchanger attenuates phase 1b ischemic arrhythmias and reperfusion-induced ventricular fibrillation. Eur J Pharmacol 2000 May 19;396(2-3):119-24

Date

05/24/2000

Pubmed ID

10822064

DOI

10.1016/s0014-2999(00)00200-4

Scopus ID

2-s2.0-0034685967 (requires institutional sign-in at Scopus site)   23 Citations

Abstract

The sodium-hydrogen exchanger-isotype 1 (NHE-1) plays a critical role in myocardial ischemia-reperfusion injury. While studies employing less selective sodium-hydrogen inhibitors have demonstrated antiarrhythmic activity, only one study has examined the in vivo efficacy of selective NHE-1 inhibition in a canine model of ischemia-reperfusion-induced arrhythmia. In the present study, the antiarrhythmic activity of Benzamide, N-(aminoiminomethyl)-4-¿4-(2-furanylcarbonyl)-1-piperazinyl -3-(methy lsulfonyl), methanesulfonate (BIIB 513), a novel NHE-1 inhibitor, was examined. An in vivo canine model of myocardial ischemia-reperfusion injury in which 60 min of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion was employed. BIIB 513 was infused either prior to ischemia or prior to reperfusion. Arrhythmias were quantified by single lead electrocardiogram. Infarct size, determined by triphenyltetrazolium staining, was expressed as a percent of the area-at-risk. In vivo, NHE-1 inhibition did not affect phase 1a arrhythmias, which occur within the first 10 min of occlusion, however, BIIB 513 significantly reduced the incidence of ischemia-induced phase 1b arrhythmias which occur between 10 and 30 min following occlusion and the incidence of reperfusion-induced ventricular fibrillation. Furthermore, NHE-1 inhibition significantly reduced infarct size, when the drug was administered either prior to ischemia or prior to reperfusion. NHE-1 inhibition selectively reduces both ischemia-induced phase 1b arrhythmias and reperfusion-induced ventricular fibrillation, and also markedly reduces myocardial infarct size when the drug is administered prior to ischemia or prior to reperfusion.

Author List

Gumina RJ, Daemmgen J, Gross GJ

MESH terms used to index this publication - Major topics in bold

Animals
Anti-Arrhythmia Agents
Arrhythmias, Cardiac
Dogs
Female
Hemodynamics
Male
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Sodium-Hydrogen Exchangers
Ventricular Fibrillation