Blocking Na(+)/H(+) exchange reduces [Na(+)](i) and [Ca(2+)](i) load after ischemia and improves function in intact hearts. Am J Physiol Heart Circ Physiol 2001 Dec;281(6):H2398-409
Date
11/16/2001Pubmed ID
11709405DOI
10.1152/ajpheart.2001.281.6.H2398Scopus ID
2-s2.0-0035661776 (requires institutional sign-in at Scopus site) 89 CitationsAbstract
We determined in intact hearts whether inhibition of Na(+)/H(+) exchange (NHE) decreases intracellular Na(+) and Ca(2+) during ischemia and reperfusion, improves function during reperfusion, and reduces infarct size. Guinea pig isolated hearts were perfused with Krebs-Ringer solution at 37 degrees C. Left ventricular (LV) free wall intracellular Na(+) concentration ([Na(+)](i)) and intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured using fluorescence dyes. Hearts were exposed to 30 min of ischemia with or without 10 microM of benzamide (BIIB-513), a selective NHE-1 inhibitor, infused for 10 min just before ischemia or for 10 min immediately on reperfusion. At 2 min of reperfusion, BIIB-513 given before ischemia decreased peak increases in [Na(+)](i) and [Ca(2+)](i), respectively, from 2.5 and 2.3 times (controls) to 1.6 and 1.3 times pre-ischemia values. At 30 min of reperfusion, BIIB-513 increased systolic-diastolic LV pressure (LVP) from 49 +/- 2% (controls) to 80 +/- 2% of pre-ischemia values. BIIB-513 reduced ventricular fibrillation by 54% and reduced infarct size from 64 +/- 1% to 20 +/- 3%. First derivative of the LVP, O(2) consumption, and cardiac efficiency were also improved by BIIB-513. Similar results were obtained with BIIB-513 given on reperfusion. These data show that Na(+) loading is a marker of reperfusion injury in intact hearts in that inhibiting NHE reduces Na(+) and Ca(2+) loading during reperfusion while improving function. These results clearly implicate the ionic basis by which inhibiting NHE protects the guinea pig intact heart from ischemia-reperfusion injury.
Author List
An J, Varadarajan SG, Camara A, Chen Q, Novalija E, Gross GJ, Stowe DFAuthors
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of WisconsinDavid F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Guinea Pigs
In Vitro Techniques
Mesylates
Myocardial Contraction
Myocardial Infarction
Myocardial Reperfusion Injury
Sodium
Sodium-Hydrogen Exchangers
Ventricular Pressure