Infliximab attenuates early myocardial dysfunction after resuscitation in a swine cardiac arrest model

Abstract

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-α has been shown to increase after successful resuscitation. We hypothesized that blocking the effects of tumor necrosis factor-α with infliximab would prevent or minimize postresuscitation cardiac dysfunction. Design: Randomized, placebo-controlled comparative study. Setting: Large animal research laboratory. Subjects: Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg). Interventions: Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest. Measurements and Main Results: Hemodynamic variables, indices of left ventricular function, and tumor necrosis factor-α 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-α increased after restoration of circulation and remained elevated throughout the observation period. Differences between groups were not significant. Interleukin-1β 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-α blockade was evident only in animals with a significant increase (doubling) in plasma tumor necrosis factor-α at 30 mins after arrest. Conclusion: Tumor necrosis factor-α plays a role in cardiac dysfunction after arrest and infliximab may attenuate or prevent postresuscitation myocardial dysfunction when administered immediately after resuscitation.