Cariporide is cardioprotective after iatrogenic ventricular fibrillation in the intact swine heart

Abstract

Background We sought to introduce sodium–hydrogen exchange inhibition as prophylaxis against the development of ventricular dysfunction in the setting of implantable cardioverter defibrillator insertion in high-risk patients. Cariporide, shown to be safe in humans, was used to reproduce previous results in our laboratory that demonstrated that sodium–hydrogen exchange inhibition preserves left ventricular (LV) function after ventricular fibrillation (VF) and reperfusion. Methods Twelve pigs (weight, 35 to 55 kg) were divided into two groups of six. Baseline ventricular function studies were based on echocardiography, conductance, aortic flow, and LV pressure. Animals were given vehicle (control) or cariporide (3 mg/kg intravenously). Ten minutes later, hearts underwent 80 seconds of VF. After reperfusion for 40 minutes, function studies were repeated. Results Postmortem examination included measuring passive pressure-volume curves and myocardial water content. Systolic indices, including preload recruitable stroke work and ejection fraction, were significantly depressed from baseline after VF and reperfusion for control animals (preload recruitable stroke work, 30.13 ± 0.59 [standard error of the mean] versus 43.85 ± 2.60 mm Hg; ejection fraction, 25.7% ± 2.4% versus 33.5% ± 3.0%) but not for those in the cariporide group (preload recruitable stroke work, 38.36 ± 1.87 versus 40.86 ± 1.45 mm Hg; ejection fraction, 33.9% ± 3.5% versus 32.8% ± 3.9%). In vivo diastolic indices demonstrated trends toward diminished ventricular compliance in control animals but not in the cariporide group after VF and reperfusion. Control animals had significantly increased postmortem LV stiffness, myocardial water content, and normalized LV mass. Conclusions Cariporide preserves LV function after 80 seconds of VF and 40 minutes of reperfusion. Cariporide may prove useful in patients with severe LV dysfunction undergoing VF for implantable cardioverter defibrillator testing.