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 Ϯ 2.5 vs 48.0 Ϯ 5.6 mm Hg [Ϯ SEM], P ϭ .001) but not in the BIIB 513 group (43.0 Ϯ 5.8 vs 45.5 Ϯ 4.1 mm Hg, P ϭ 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 Ϯ 15 vs 88 Ϯ 14 seconds [Ϯ SEM], P ϭ .008). Myocardial water content (78.97% Ϯ 0.94% vs 77.86% Ϯ 0.46% [Ϯ SEM]) and normalized left ventricular mass (137.24 Ϯ 6.17 vs 128.41 Ϯ 1.96 g [Ϯ 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. I mplantable cardioverter-defibrillators (ICDs) are effective treatment for refractory malignant arrhythmias, decreasing the incidence of sudden arrhythmic death to 1% to 2% per year. [1][2][3] Insertion requires induction of ventricular fibrillation (VF) to measure defibrillation thresholds (DFTs). ICD recipients often have markedly decreased ventricular function caused by cardiomyopathy, infarct-related scars, or left ventricular (LV) aneurysms. 1 Although perioperative mortality for routine ICD insertion is low (0.5%-From the Departments of Surgery, a Pediatrics, b and Biostatistics,

Na+/H+ exchange inhibition and antioxidants lack additive protective effects after reperfusion injury in the working heterotopic rat heart isograft

“…Another study from our laboratory has correlated postmortem passive LV pressure-volume relations with in vivo diastolic properties. 27 We believe this validates the use of postmortem passive pressure-volume relations as a barometer of myocardial injury despite the fact that diastolic function is an active process.…”