David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
Resuscitation. 2013 Jan;84(1):103-7. doi: 10.1016/j.resuscitation.2012.05.021. Epub 2012 Jun 7.
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.
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.
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).
Blockade of TNF-α in the immediate post-ROSC period improved survival and hemodynamic parameters in this swine model of ischemic VF.
炎症细胞因子与心脏骤停后综合征的病理生理学有关，包括心肌功能障碍和低血压，这通常导致多器官系统功能障碍和死亡。我们假设，在自主循环恢复（ROSC）后给予英夫利昔单抗治疗可以改善低血压和心肌功能障碍，并延长生存时间。
对家猪进行麻醉和仪器操作。在第一间隔穿支远端将 LAD 冠状动脉球囊闭塞，并使所有动物自然发生室颤。7 分钟后，进行胸外按压、除颤和标准 ACLS 复苏。ROSC 后（n=32）的动物随机接受英夫利昔单抗（5mg/kg，n=16）或载体（250mL 生理盐水，n=16）治疗，并在 3 小时内监测存活和血流动力学情况。
两组在复苏前的血流动力学变量、TNF-α 水平或复苏变量均无差异。两组在 ROSC 后均出现平均动脉压（MAP）和每搏功（SW）的时间依赖性下降，最低点在 1 小时，随后在 2 小时和 3 小时恢复。在接受英夫利昔单抗治疗的猪中，这种下降被减轻（1 小时时 MAP 的组间差异为 21mmHg，95%CI 3-38mmHg 和 SW 为 6.7gm-m，95%CI 0.4-13mmHg）。在载体组中，左心室收缩 dp/dt 下降（-437mmHg/s，95%CI -183 至-690），但在英夫利昔单抗组中没有下降。载体组的 Tau 仅升高（44ms，95%CI 1-87）。英夫利昔单抗组的短期生存率更高（Kaplan-Meier p=0.022）。
在缺血性 VF 猪模型中，ROSC 后即刻阻断 TNF-α 可提高生存率和血流动力学参数。
