Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, Kiel, 24105, Germany.
Crit Care. 2010;14(1):R21. doi: 10.1186/cc8879. Epub 2010 Feb 16.
Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation.
Thirty pigs (28 to 34 kg) were subjected to cardiac arrest following temporary coronary artery occlusion. After seven minutes of ventricular fibrillation and two minutes of basic life support, advanced cardiac life support was started according to the current American Heart Association guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques.
Global cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/- 2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham control). Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also confirmed for IL-1beta on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.
Mild therapeutic hypothermia resulted in decreased expression of typical cerebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.
低温可提高心脏骤停后患者的生存率和神经恢复。促炎细胞因子已被认为与局灶性脑缺血/再灌注损伤有关。目前尚不清楚心脏骤停是否也会触发脑内炎症分子的释放,以及治疗性低温是否会改变这种炎症反应。本研究旨在探讨低温或低温与七氟醚麻醉后处理联合应用是否会影响心肺复苏后大脑的炎症反应。
30 只(28-34kg)猪在短暂性冠状动脉闭塞后发生心脏骤停。在心室颤动 7 分钟和基础生命支持 2 分钟后,根据当前的美国心脏协会指南开始进行高级心脏生命支持。21 只动物恢复自主循环,随机分为常温(38°C)组、低温(33°C)组或低温(33°C)联合七氟醚(每组 n = 7)24 小时。采用 RT-PCR 和 ELISA 技术检测心肺复苏后 24 小时处死的猪大脑皮质组织样本,研究低温和低温联合七氟醚对大脑炎症反应的影响。
复苏后全脑缺血导致大脑组织炎性细胞因子 mRNA 表达显著上调(平均 +/- SD;白细胞介素(IL)-1β 8.7 +/- 4.0,IL-6 4.3 +/- 2.6,IL-10 2.5 +/- 1.6,肿瘤坏死因子(TNF)α 2.8 +/- 1.8,细胞间黏附分子-1(ICAM-1)4.0 +/- 1.9 倍与假手术对照相比)和 IL-1β 蛋白浓度(与假手术对照相比,1.9 +/- 0.6 倍)。低温与大脑炎性细胞因子 mRNA 表达显著降低有关(IL-1β 1.7 +/- 1.0,IL-6 2.2 +/- 1.1,IL-10 0.8 +/- 0.4,TNFalpha 1.1 +/- 0.6,ICAM-1 1.9 +/- 0.7 倍与假手术对照相比)。IL-1β 蛋白水平也证实了这一结果。采用低温联合七氟醚的实验设置表明,与单独低温相比,挥发性麻醉剂并没有提供额外的抗炎作用。
心肺复苏后,轻度治疗性低温可降低典型脑内炎症介质的表达。这可能至少部分解释了全脑缺血和再灌注后神经保护的作用。