Na(+)/H(+) exchange inhibition prevents endothelial dysfunction after I/R injury. Am J Physiol Heart Circ Physiol 2001 Sep;281(3):H1260-6
Date
08/22/2001Pubmed ID
11514295DOI
10.1152/ajpheart.2001.281.3.H1260Scopus ID
2-s2.0-0034834920 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Whereas inhibition of the Na(+)/H(+) exchanger (NHE) has been demonstrated to reduce myocardial infarct size in response to ischemia-reperfusion injury, the ability of NHE inhibition to preserve endothelial cell function has not been examined. This study examined whether NHE inhibition could preserve endothelial cell function after 90 min of regional ischemia and 180 min of reperfusion and compared this inhibition with ischemic preconditioning (IPC). In a canine model either IPC, produced by one 5-min coronary artery occlusion (1 x 5'), or the specific NHE-1 inhibitor eniporide (EMD-96785, 3.0 mg/kg) was administered 15 min before a 90-min coronary artery occlusion followed by 3 h of reperfusion. Infarct size (IS) was determined by 2,3,5-triphenyl tetrazolium chloride staining and expressed as a percentage of the area-at-risk (IS/AAR). Endothelial cell function was assessed by measurement of coronary blood flow in response to intracoronary acetylcholine infusion at the end of reperfusion. Whereas neither control nor IPC-treated animals exhibited a significant reduction in IS/AAR or preservation of endothelial cell function, animals treated with the NHE inhibitor eniporide showed a marked reduction in IS/AAR and a significantly preserved endothelial cell function (P < 0.05). Thus NHE-1 inhibition is more efficacious than IPC at reducing IS/AAR and at preserving endothelial cell function in dogs.
Author List
Gumina RJ, Moore J, Schelling P, Beier N, Gross GJMESH terms used to index this publication - Major topics in bold
AcetylcholineAnimals
Coronary Circulation
Coronary Vessels
Dogs
Endothelium, Vascular
Guanidines
Heart Ventricles
Hemodynamics
Ischemic Preconditioning, Myocardial
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion
Organ Size
Reperfusion Injury
Sodium-Hydrogen Exchangers
Sulfones
