Lahoud-Rahme Manuella S, Stezoski Jason, Kochanek Patrick M, Melick John, Tisherman Samuel A, Drabek Tomas
Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, United States.
Resuscitation. 2009 Apr;80(4):484-8. doi: 10.1016/j.resuscitation.2009.01.007. Epub 2009 Feb 8.
Emergency Preservation and Resuscitation (EPR) represents a novel approach to treat exsanguination cardiac arrest (CA) victims, using an aortic flush to induce hypothermia during circulatory arrest, followed by delayed resuscitation with cardiopulmonary bypass (CPB). The status of the blood-brain barrier (BBB) integrity after prolonged hypothermic CA is unclear. The objective of this study was to assess BBB permeability in two EPR models in rats, associated with poor outcome. Rats subjected to traumatic brain injury (TBI) and naïve rats served as positive and negative controls, respectively.
The BBB will be disrupted after TBI, but intact after prolonged hypothermic CA.
Four groups were studied: (1) EPR-IC (ice cold)-75 min CA at 15 degrees C; (2) EPR-RT (room temperature)-20 min CA at 28 degrees C; (3) TBI; (4) sham. Rats in EPR groups were subjected to rapid hemorrhage, followed by CA. Rats in the TBI group had a controlled cortical impact to the left hemisphere. Naïves were subjected to the same anesthesia and surgery. 1h after insult, rats were injected with Evans Blue (EB), a marker of BBB permeability for albumin. Rats were sacrificed after 5h and EB absorbance was quantified in brain samples.
TBI produced an approximately 10-fold increase in EB absorbance in the left (injured) hemisphere vs. left hemisphere for all other groups (p=0.001). In contrast, EB absorbance in either EPR group did not differ from sham.
BBB integrity to albumin is not disrupted early after resuscitation from prolonged CA treated with EPR. Neuroprotective adjuncts to hypothermia in this setting should focus on agents that penetrate the BBB. These findings also have implications for deep hypothermic circulatory arrest.
紧急保存与复苏（EPR）是一种治疗失血性心脏骤停（CA）患者的新方法，即在循环骤停期间通过主动脉冲洗诱导低温，随后进行体外循环（CPB）延迟复苏。长时间低温CA后血脑屏障（BBB）完整性的状态尚不清楚。本研究的目的是评估大鼠两种EPR模型中与不良预后相关的BBB通透性。遭受创伤性脑损伤（TBI）的大鼠和未受伤的大鼠分别作为阳性和阴性对照。
TBI后BBB会被破坏，但长时间低温CA后BBB保持完整。
研究分为四组：（1）EPR-IC（冰冷）-在15℃下进行75分钟CA；（2）EPR-RT（室温）-在28℃下进行20分钟CA；（3）TBI；（4）假手术组。EPR组的大鼠先快速出血，然后发生CA。TBI组的大鼠对左半球进行可控性皮质撞击。未受伤的大鼠接受相同的麻醉和手术。损伤后1小时，给大鼠注射伊文思蓝（EB），这是一种白蛋白BBB通透性的标志物。5小时后处死大鼠，对脑样本中EB的吸光度进行定量分析。
与所有其他组的左半球相比，TBI使左（受伤）半球的EB吸光度增加了约10倍（p=0.001）。相比之下，EPR组中任何一组的EB吸光度与假手术组无差异。
经EPR治疗的长时间CA复苏后早期，白蛋白的BBB完整性未被破坏。在这种情况下，低温的神经保护辅助措施应侧重于能够穿透BBB的药物。这些发现对深度低温循环骤停也有启示。
