Na(+)/H(+) exchange inhibition-induced cardioprotection in dogs: effects on neutrophils versus cardiomyocytes.

Gumina RJ, Auchampach J, Wang R, Buerger E, Eickmeier C, Moore J, Daemmgen J, Gross GJ
Am J Physiol Heart Circ Physiol. 2000 279 (4): H1563-70

PMID: 11009442 · DOI:10.1152/ajpheart.2000.279.4.H1563

Numerous studies have examined the effect of Na(+)/H(+) exchanger (NHE) inhibition on the myocardium; however, the effect of NHE-1 inhibition on neutrophil function has not been adequately examined. An in vivo canine model of myocardial ischemia-reperfusion injury in which 60 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion was used to examine the effect of NHE-1 inhibition on infarct size (IS) and neutrophil function. BIIB-513, a selective inhibitor of NHE-1, was infused before ischemia. IS was expressed as a percentage of area at risk (IS/AAR). NHE-1 inhibition significantly reduced IS/AAR and reduced neutrophil accumulation in the ischemic myocardium. NHE-1 inhibition attenuated both phorbol 12-myristate 13-acetate- and platelet-activating factor-induced neutrophil respiratory burst but not CD18 upregulation. Furthermore, NHE-1 inhibition directly protected cardiomyocytes against metabolic inhibition-induced lactate dehydrogenase release and hypercontracture. This study provides evidence that the cardioprotection induced by NHE-1 inhibition is likely due to specific protection of cardiomyocytes and attenuation of neutrophil activity.

MeSH Terms (16)

Animals CD18 Antigens Collateral Circulation Coronary Circulation Dogs Gases Heart Hemodynamics Mesylates Myocardial Infarction Myocardial Ischemia Myocardial Reperfusion Injury Myocardium Neutrophils Peroxidase Sodium-Hydrogen Exchangers

Connections (1)

This publication is referenced by other Labnodes entities: