Extracorporeal Versus Conventional Cardiopulmonary Resuscitation After Ventricular Fibrillation Cardiac Arrest in Rats: A Feasibility Trial

Extracorporeal Versus Conventional Cardiopulmonary Resuscitation After Ventricular Fibrillation Cardiac Arrest in Rats: A Feasibility Trial
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DOI:
10.1097/ccm.0b013e318287f51e
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发表时间:
2013-09-01
影响因子:
8.8
通讯作者:
Kochanek, Patrick M.
Kochanek, Patrick M.
中科院分区:
医学1区
文献类型:
--
作者:
Janata, Andreas;Magnet, Ingrid A. M.;Kochanek, Patrick M.

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目的:体外循环心肺复苏术为心脏骤停复苏提供了脑再灌注、心血管支持和温度控制。我们假设大鼠室颤心脏骤停后体外心肺复苏是可行的,并且与传统心肺复苏相比可以改善结果。设计:前瞻性随机研究。地点:大学实验室。受试者:成年雄性Sprague-Dawley大鼠。干预措施:无。测量和主要结果:大鼠(插管,装有动脉和静脉导管和心肺转流插管)随机接受常规心肺复苏,体外心肺复苏联合/不联合治疗性低温或假手术组。室颤心脏骤停6分钟后,使用药物(肾上腺素、碳酸氢钠和肝素)、通气、心肺复苏或体外心肺复苏和除颤进行复苏。恢复自主循环后,将温度保持在37.0 ℃或33.0 ℃ 12小时。神经功能缺损评分、总体性能分类、组织学损伤评分(第14天时CA1海马中的活神经元计数;假手术组的%),和-小胶质细胞增殖和活化(Iba-1免疫组化)进行评估。体外心肺复苏比体表降温更快地诱导低温(P <0.05),但心率在体外心肺复苏低温组最低(P <0.05)。各组之间的存活率、神经功能缺损评分、总体表现类别和CA1中存活的神经元无差异。14天时,低温显著减少下托和丘脑的神经元损伤,并增加CA 1的小胶质细胞反应(所有p <0.05)。体外心肺复苏与心肺复苏对任何脑区的损伤没有任何益处,体外心肺复苏与低温无协同效益。结论:在6分钟室颤心脏骤停的大鼠模型中,心肺复苏或体外心肺复苏导致神经功能完好的生存。12小时的轻度低温减弱了下托和丘脑的神经元死亡,但没有CA1,令人惊讶的是,增加了小胶质细胞的反应。在大鼠模型中,从室颤心脏骤停和严格的温度控制与体外心肺复苏是可行的,局部神经保护,并改变神经炎症与标准复苏。实验性体外心肺复苏的使用应采用较长的损伤持续时间进行探索。
Objectives: Extracorporeal cardiopulmonary resuscitation with cardiopulmonary bypass potentially provides cerebral reperfusion, cardiovascular support, and temperature control for resuscitation from cardiac arrest. We hypothesized that extracorporeal cardiopulmonary resuscitation is feasible after ventricular fibrillation cardiac arrest in rats and improves outcome versus conventional cardiopulmonary resuscitation.Design: Prospective randomized study.Setting : University laboratory.Subjects: Adult male Sprague-Dawley rats.Interventions: None.Measurements and Main Results: Rats (intubated, instrumented with arterial and venous catheters and cardiopulmonary bypass cannulae) were randomized to conventional cardiopulmonary resuscitation, extracorporeal cardiopulmonary resuscitation with/without therapeutic hypothermia, or sham groups. After 6 minutes of ventricular fibrillation cardiac arrest, resuscitation was performed with drugs (epinephrine, sodium bicarbonate, and heparin), ventilation, either cardiopulmonary resuscitation or extracorporeal cardiopulmonary resuscitation, and defibrillation. Temperature was maintained at 37.0 degrees C or 33.0 degrees C for 12 hours after restoration of spontaneous circulation. Neurologic deficit scores, overall - performance category, histological damage scores (viable neuron counts in CA1 hippocampus at 14 days; % of sham), and - microglia proliferation and activation (Iba-1 immunohistochemistry) were assessed.Results: Extracorporeal cardiopulmonary resuscitation induced hypothermia more rapidly than surface cooling (p < 0.05), although heart rate was lowest in the extracorporeal cardiopulmonary resuscitation hypothermia group (p < 0.05). Survival, neurologic deficit scores, overall performance category, and surviving neurons in CA1 did not differ between groups. Hypothermia significantly reduced neuronal damage in subiculum and thalamus and increased the microglial response in CA1 at 14 days (all p < 0.05). There was no benefit from extracorporeal cardiopulmonary resuscitation versus cardiopulmonary resuscitation on damage in any brain region and no synergistic benefit from extracorporeal cardiopulmonary resuscitation with hypothermia.Conclusions: In a rat model of 6-minute ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation or extracorporeal cardiopulmonary resuscitation leads to survival with intact neurologic outcomes. Twelve hours of mild hypothermia attenuated neuronal death in subiculum and thalamus but not CA1 and, surprisingly, increased the microglial response. Resuscitation from ventricular fibrillation cardiac arrest and rigorous temperature control with extracorporeal cardiopulmonary resuscitation in a rat model is feasible, regionally neuroprotective, and alters neuroinflammation versus standard resuscitation. The use of experimental extracorporeal cardiopulmonary resuscitation should be explored using longer insult durations.