Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA.
Crit Care Med. 2010 Apr;38(4):1162-7. doi: 10.1097/CCM.0b013e3181d44324.
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.
Randomized, placebo-controlled comparative study.
Large animal research laboratory.
Twenty-eight anesthetized and instrumented domestic male swine (Yorkshire and Yorkshire/Hampshire mix; weight, 35-45 kg).
Infusion of infliximab (5 mg/kg) or normal saline after resuscitation from ventricular fibrillation cardiac arrest.
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.
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.
心肺复苏成功后左心室功能障碍导致复苏后早期死亡。已知促炎细胞因子可降低心肌功能，且肿瘤坏死因子-α在复苏成功后会增加。我们假设用英夫利昔单抗阻断肿瘤坏死因子-α的作用将预防或最小化复苏后心功能障碍。
随机、安慰剂对照比较研究。
大型动物研究实验室。
28 只麻醉和仪器化的雄性家猪（约克夏和约克夏/汉普郡混合；体重 35-45 公斤）。
复苏后从心室颤动心脏骤停中输注英夫利昔单抗（5mg/kg）或生理盐水。
在复苏后早期（3 小时），在心脏骤停 8 分钟期间测量血流动力学变量、左心室功能指数和肿瘤坏死因子-α。在自主循环恢复后 5 分钟内，14 只动物接受英夫利昔单抗，5mg/kg，在 30 分钟内输注。14 只动物接受生理盐水输注。复苏后两组均未给予正性肌力药和血管加压药。在观察期间，肿瘤坏死因子-α在两组中均增加并持续升高。两组之间的差异无统计学意义。在观察期间，两组研究中白细胞介素-1β浓度均无明显变化。在复苏后 30 分钟内，英夫利昔单抗组的平均动脉压和每搏功明显更大，这些差异在整个复苏后 3 小时期间持续存在。肿瘤坏死因子-α阻断的作用仅在复苏后 30 分钟时血浆肿瘤坏死因子-α显著增加（翻倍）的动物中明显。
肿瘤坏死因子-α在心脏骤停后心功能障碍中起作用，并且英夫利昔单抗在复苏后立即给药时可能减轻或预防复苏后心肌功能障碍。
