Na(+)/H(+) exchange inhibition-induced cardioprotection in dogs: effects on neutrophils versus cardiomyocytes. Am J Physiol Heart Circ Physiol 2000 Oct;279(4):H1563-70
Date
09/29/2000Pubmed ID
11009442DOI
10.1152/ajpheart.2000.279.4.H1563Scopus ID
2-s2.0-0033712090 (requires institutional sign-in at Scopus site) 48 CitationsAbstract
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.
Author List
Gumina RJ, Auchampach J, Wang R, Buerger E, Eickmeier C, Moore J, Daemmgen J, Gross GJAuthor
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD18 Antigens
Collateral Circulation
Coronary Circulation
Dogs
Gases
Heart
Hemodynamics
Mesylates
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Myocardium
Neutrophils
Peroxidase
Sodium-Hydrogen Exchangers
