title: Sodium-hydrogen exchange inhibition preserves ventricular function after ventricular fibrillation in the intact swine heart.
abstract: BACKGROUND
  We tested the hypothesis that sodium-hydrogen exchange inhibition attenuates ventricular dysfunction after ischemia-reperfusion injury in the intact porcine heart.
  
  
  METHODS
  Twelve pigs (weight, 30-45 kg) were evenly divided into 2 groups. Baseline ventricular function studies were based on echocardiography, conductance, aortic flow, and left ventricular pressure. Animals were given vehicle (control) or benzamide-N-(aminoiminomethl)-4-(4-[2-furanylcarbonyl]-1-piperazinyl)-3-(methylsulfonyl)methanesulfonate (BIIB 513; 3 mg/kg administered intravenously). Ten minutes later, hearts were subjected to 75 seconds of ventricular fibrillation. After reperfusion for 40 minutes, function studies were repeated. Hearts were arrested and excised. Postmortem data included passive pressure-volume curves and myocardial water content.
  
  
  RESULTS
  Preload recruitable stroke work was significantly decreased from baseline after ischemia and reperfusion in the control group (27.7 +/- 2.5 vs 48.0 +/- 5.6 mm Hg [+/- SEM], P =.001) but not in the BIIB 513 group (43.0 +/- 5.8 vs 45.5 +/- 4.1 mm Hg, P = not significant). In vivo diastolic and postmortem passive left ventricular compliance were reduced after ischemia and reperfusion for control animals but remained unchanged for animals receiving BIIB 513. Time required to recover baseline blood pressure after ventricular fibrillation was significantly longer for control animals (159 +/- 15 vs 88 +/- 14 seconds [+/- SEM], P =.008). Myocardial water content (78.97% +/- 0.94% vs 77.86% +/- 0.46% [+/- SEM]) and normalized left ventricular mass (137.24 +/- 6.17 vs 128.41 +/- 1.96 g [+/- SEM]) were insignificantly increased in control animals.
  
  
  CONCLUSIONS
  Sodium-hydrogen exchange inhibition attenuates ventricular dysfunction after 75 seconds of ventricular fibrillation and 40 minutes of reperfusion. This family of agents might prove useful in patients with severe left ventricular dysfunction undergoing ventricular fibrillation for implantable cardioverter defibrillator testing.
authors.affiliation: Department of Surgery, Columbia College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Rabkin
authors.forename: Santos E
authors.initials: SE
authors.lastname: Cabreriza
authors.forename: Jared C
authors.initials: JC
authors.lastname: Lacorte
authors.forename: Alan D
authors.initials: AD
authors.lastname: Weinberg
authors.forename: Lindita
authors.initials: L
authors.lastname: Coku
authors.forename: Rowan
authors.initials: R
authors.lastname: Walsh
authors.forename: Ralph
authors.initials: R
authors.lastname: Mosca
authors.forename: Henry M
authors.initials: HM
authors.lastname: Spotnitz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008698:Mesylates / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D008698:Mesylates; D017923:Sodium-Hydrogen Exchangers; C402725:BIIB 513