Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model.
OBJECTIVE
Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death after resuscitation. Proinflammatory cytokines are known to decrease myocardial function, and tumor necrosis factor-alpha has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of tumor necrosis factor-alpha with infliximab would prevent or minimize postresuscitation cardiac dysfunction.


METHODS
Randomized, placebo-controlled comparative study.


METHODS
Large animal research laboratory.


METHODS
Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg).


METHODS
Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest.


RESULTS
Hemodynamic variables, indices of left ventricular function, and tumor necrosis factor-alpha were measured before and after 8 mins of cardiac arrest during the early postresuscitation period (3 hrs). Within 5 mins of restoration of spontaneous circulation, 14 animals received infliximab, 5 mg/kg, infused over 30 mins. Fourteen animals received an infusion of normal saline. Inotropes and vasopressors were not administered to either group after resuscitation. Tumor necrosis factor-alpha increased after restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. Interleukin-1beta concentration did not change significantly during the observation period in either study group. Mean arterial pressure and stroke work were significantly greater in the infliximab group within 30 mins of resuscitation, and these differences were sustained throughout the 3-hr postresuscitation period. The effect of tumor necrosis factor-alpha blockade was evident only in animals with a significant increase (doubling) in plasma tumor necrosis factor-alpha at 30 mins after arrest.


CONCLUSIONS
Tumor necrosis factor-alpha plays a role in cardiac dysfunction after arrest and infliximab may attenuate or prevent postresuscitation myocardial dysfunction when administered immediately after resuscitation.
Niemann
James T
JT
Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA. jniemann@emedharbor.edu
Youngquist
Scott
S
Rosborough
John P
JP
Shah
Atman P
AP
Phan
Quynh T
QT
Filler
Scott G
SG
D000818:Animals; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006323:Heart Arrest / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D000069285:Infliximab; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab