Journal
RESUSCITATION
Volume 84, Issue 1, Pages 103-107Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.resuscitation.2012.05.021
Keywords
Cardiopulmonary resuscitation; Ventricular fibrillation; Post-resuscitation period; Inflammatory response
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Funding
- NIH NHLBI [R01 HL076671]
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Aim of the study: 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: Domestic swine were anesthetized and instrumented. Balloon occlusion of the LAD coronary artery just distal to the first septal perforator was performed and VF followed spontaneously in all animals. After 7 min, 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 h. Results: There were no differences in prearrest hemodynamic variables, TNF-alpha 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 h followed by recovery over hours 2 and 3. This decline was blunted in infliximab-treated swine (1-h between group difference in MAP 21 mm Hg, 95% CI 3-38 mm Hg and SW 6.7 gm-m, 95% CI 0.4-13 at 1 h). Left ventricular systolic dp/dt fell in the vehicle group (-437 mm Hg/s, 95% CI -183 to -690) but did not in the infliximab group. Tau rose only in the vehicle group (44 ms, 95% CI 1-87). Short-term survival was higher in the infliximab group (Kaplan-Meier p = 0.022). Conclusions: Blockade of TNF-alpha in the immediate post-ROSC period improved survival and hemodynamic parameters in this swine model of ischemic VF. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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