Abstract 80: Infliximab Is Superior to Etanercept for the Treatment of Postresuscitation Myocardial Dysfunction in a Swine Model of Ventricular Fibrillation

Abstract

Introduction: Infliximab, a monoclonal antibody directed against the inflammatory cytokine TNF-α, has been shown to attenuate the myocardial dysfunction and hemodynamic decompensation associated with post-cardiac arrest syndrome. The aim of this study was to compare the effects of etanercept, a TNF-α receptor antagonist, to infliximab in a swine model of ventricular fibrillation (VF). Methods: Under general anesthesia, VF was induced electrically in domestic swine (n=30). After 7 minutes of VF, standard ACLS resuscitation was performed. Animals achieving return of spontaneous circulation (ROSC) were randomized to immediately receive infliximab (5 mg/kg, n=10) or etanercept (0.3 mg/kg [4 mg/m2], n=10) or vehicle (250 mL normal saline [NS], n=10) and LV function and hemodynamics were monitored for 3 hours. Results: Following ROSC, mean arterial pressure (MAP), stroke work (SW), and LV dP/dt fell from prearrest values in all groups. However, at the 30 minute nadir, infliximab-treated animals had higher MAP than either the NS group (difference 14.4 mm Hg, 95% confidence interval [CI] 4.2-24.7) or the etanercept group (19.2 mm Hg, 95% CI 9.0-29.5), higher SW than the NS group (10.3 gm-m, 95% CI 5.1-15.5, Figure) or the etanercept group (8.9 gm-m, 95% CI 4.0-14.4) and greater LV dP/dt than the NS group (282.9 mm Hg/sec, 95% CI 169.6-386.1) or the etanercep group (228.9 mm Hg/sec, 95% CI 115.6-342.2). Conclusions: In conclusion, only infliximab demonstrated a beneficial effect on post cardiac arrest hemodynamics and LV function in this swine model. Etanercept was no better in this regard than saline.