Drabek Tomas, Stezoski Jason, Garman Robert H, Wu Xianren, Tisherman Samuel A, Stezoski S William, Fisk Jesse A, Jenkins Larry, Kochanek Patrick M
Safar Center for Resuscitation Research, and the Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Crit Care Med. 2007 Feb;35(2):532-7. doi: 10.1097/01.CCM.0000253398.61666.0D.
Emergency preservation and resuscitation (EPR) comprise a novel approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass. Development of a rat EPR model would enable study of the molecular mechanisms of neuronal injury and the screening of novel agents for emergency preservation.
A prospective, randomized study.
University research facility.
Adult male Sprague-Dawley rats.
Isoflurane-anesthetized rats were subjected to lethal hemorrhage (12.5 mL for 5 mins), followed by KCl-induced cardiac arrest and 1 min of no flow. Three groups (n=6) were studied: hypothermic EPR (H-EPR; 0 degrees C flush; target temperature, 15 degrees C); normothermic EPR (N-EPR; 38 degrees C flush); and controls. After 20 mins of H-EPR or N-EPR, resuscitation was initiated with cardiopulmonary bypass for 60 mins and mechanical ventilation. Controls were subjected to complete experimental preparation and anesthesia without cardiac arrest, followed by 60 mins of cardiopulmonary bypass and mechanical ventilation. Surviving rats were extubated 2 hrs later. Survival, Overall Performance Category (1, normal; 5, death), Neurologic Deficit Score, Histologic Damage Score, and biochemistry were assessed in survivors on day 7.
All rats in H-EPR and control groups survived, whereas none of the rats in the N-EPR group had restoration of spontaneous circulation. All rats in the H-EPR and control groups achieved Overall Performance Category 1, normal Neurologic Damage Score, and normal or near normal Histologic Damage Score and biochemical markers of organ injury.
We have established an EPR model in rats showing no neurologic injury, despite an exsanguination cardiac arrest, followed by 20 mins of EPR using miniaturized cardiopulmonary bypass. Establishment of this model should facilitate application of molecular tools to study the effects of hypothermic preservation and reperfusion and to screen novel pharmacologic adjuncts.
紧急保存与复苏（EPR）是一种用于救治失血性心脏骤停患者的新方法。EPR采用冷主动脉灌注诱导深度低温保存，随后进行体外循环复苏。建立大鼠EPR模型将有助于研究神经元损伤的分子机制以及筛选用于紧急保存的新型药物。
一项前瞻性随机研究。
大学研究机构。
成年雄性Sprague-Dawley大鼠。
用异氟烷麻醉大鼠，使其遭受致死性出血（12.5 mL，持续5分钟），随后诱导氯化钾致心脏骤停并停跳1分钟。研究了三组（每组n = 6）：低温EPR（H-EPR；0℃灌注；目标温度15℃）；常温EPR（N-EPR；38℃灌注）；以及对照组。H-EPR或N-EPR 20分钟后，开始进行60分钟的体外循环复苏和机械通气。对照组进行完整的实验准备和麻醉，但不发生心脏骤停，随后进行60分钟的体外循环和机械通气。存活的大鼠在2小时后拔管。在第7天对存活大鼠的存活率、总体表现类别（1，正常；5，死亡）、神经功能缺损评分、组织学损伤评分和生化指标进行评估。
H-EPR组和对照组的所有大鼠均存活，而N-EPR组的大鼠无一恢复自主循环。H-EPR组和对照组的所有大鼠总体表现类别均为1，神经损伤评分正常，组织学损伤评分及器官损伤生化标志物正常或接近正常。
我们在大鼠中建立了EPR模型，尽管发生了失血性心脏骤停，但经20分钟的小型体外循环EPR后未出现神经损伤。该模型的建立应有助于应用分子工具研究低温保存和再灌注的影响，并筛选新型药理学辅助药物。
