TNF-α blockade improves early post-resuscitation survival and hemodynamics in a swine model of ischemic ventricular fibrillation.
OBJECTIVE
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-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 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-α in the immediate post-ROSC period improved survival and hemodynamic parameters in this swine model of ischemic VF.
David Geffen School of Medicine at UCLA, Los Angeles, CA, United States. jniemann@emedharbor.edu
James T
JT
Niemann
Scott T
ST
Youngquist
Atman P
AP
Shah
Joseph L
JL
Thomas
John P
JP
Rosborough
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D006439:Hemodynamics; D000069285:Infliximab; D011897:Random Allocation; D015996:Survival Rate; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors*; D014693:Ventricular Fibrillation / Q000628:therapy*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab