Abstract 10: TNF-α Blockade Improves Early Post-ROSC Survival and Hemodynamics in the Swine Model of Ischemic Ventricular Fibrillation
Introduction: Inflammatory cytokines have been implicated in the pathophysiology of post cardiac arrest syndrome, including myocardial dysfunction and hypotension, often leading to multi-organ system dysfunction and death. We hypothesized that administration of infliximab after return of spontaneous circulation (ROSC) would ameliorate hypotension and myocardial dysfunction and prolong survival.
Methods: Adolescent male swine (weight 36 kg) were anesthetized and instrumented. Balloon occlusion of the LAD coronary artery just distal to the first septal perforator was performed and ventricular fibrillation (VF) followed spontaneously in all animals. After 7-minutes, manual chest compressions, defibrillation, and standard ACLS resuscitation was performed. Animals achieving ROSC (N=32) were randomized to receive infliximab (5 mg/kg, n=16) or vehicle (250 mL normal saline, n=16) immediately post-ROSC and survival and hemodynamics were monitored for 3 hours.
Results: There were no differences in prearrest hemodynamic variables, TNF-α levels, or resuscitation variables between groups. Both groups demonstrated a time dependent decline in mean arterial pressure (MAP) and stroke work (SW) post-ROSC with a nadir at 1 hour followed by recovery over hours 2 and 3. This decline was blunted in infliximab-treated swine (1-hour between group difference in MAP of 27 mmHg, 95% CI 2-52 and difference in SW of 8 gm-m, 95% CI 1-15). The time derivative of LV pressure, dPdT, fell in the vehicle group (-439 mm Hg/sec, 95% CI -223 to -656) but did not in the infliximab group. Tau, the time constant for isovolumic relaxation, rose only in the vehicle group (increase of 44 msec, 95% CI 8-80). Short-term survival was higher in the infliximab group (Kaplan-Meier Figure 1).
Conclusions: Blockade of TNF-α in the immediate post-ROSC period improved hemodynamic parameters and short-term survival in this swine model of ischemic VF.
- Cardiopulmonary resuscitation
- Ventricular fibrillation
- Post cardiac arrest care
- Post cardiac resuscitation
- © 2011 by American Heart Association, Inc.