Na+/H+ exchange inhibition-induced cardioprotection in dogs: Effects on neutrophils versus cardiomyocytes

Richard J. Gumina, John Auchampach, Rongang Wang, Erich Buerger, Christian Eickmeier, Jeannine Moore, Juergen Daemmgen, Garrett J. Gross

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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 ischemiareperfusion 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.

Original languageEnglish (US)
Pages (from-to)H1563-H1570
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number4 48-4
Publication statusPublished - Dec 7 2000

    Fingerprint

Keywords

  • Myocardial infarction
  • Sodium-hydrogen exchange
  • Sodiumhydrogen exchanger-1

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Gumina, R. J., Auchampach, J., Wang, R., Buerger, E., Eickmeier, C., Moore, J., ... Gross, G. J. (2000). Na+/H+ exchange inhibition-induced cardioprotection in dogs: Effects on neutrophils versus cardiomyocytes. American Journal of Physiology - Heart and Circulatory Physiology, 279(4 48-4), H1563-H1570.