Abstract P148: Infliximab Attenuates Early Postresuscitation Myocardial Dysfunction in a Swine Cardiac Arrest Model
BACKGROUND: Left ventricular (LV) dysfunction after cardiopulmonary resuscitation contributes to early death following resuscitation. Proinflammatory cytokines are known to depress myocardial function and TNF-alpha increases after successful resuscitation. We hypothesized that blocking the effects of TNF-alpha would ameliorate postresuscitation cardiac dysfunction.
METHODS AND RESULTS: Hemodynamic variables, indices of LV function, and TNF-alpha were measured in anesthetized and instrumented swine before and after 8 min of cardiac arrest during the early post-resuscitation period (3 hrs). Within 5 min of restoration of spontaneous circulation (ROSC), 14 animals received infliximab, 5 mg/kg, infused over 30 min. Fourteen animals received no treatment. Inotropes and vasopressors were not administered to either group following resuscitation. TNF-alpha increased following ROSC and remained elevated throughout the observation period. Differences between groups were not significant. IL-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 TNF-α blockade was evident only in animals with a significant increase (doubling) in plasma TNF-α at 30 minutes post-arrest (TNF responders).
CONCLUSION: TNF-α plays a role in post-arrest cardiac dysfunction and Infliximab may attenuate or prevent postresuscitation myocardial dysfunction when given immediately after resuscitation.