Neurologic preservation by Na+-H+ exchange inhibition prior to 90 minutes of hypothermic circulatory arrest
Neurologic preservation by Na+-H+ exchange inhibition prior to 90 minutes of hypothermic circulatory arrest
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DOI：
10.1016/j.athoracsur.2004.07.007
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发表时间：
2005-02-01
影响因子：
4.6
通讯作者：
Tan, ZT
中科院分区：
文献类型：
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作者：
Castellá, M;Buckberg, GD;Tan, ZT
背景在低温停搏的脑缺血-再灌注模型中研究了Cariporide（HOE 642 Aventis Pharma，斯特拉斯堡- Cedex，France）（一种Na+-H+交换器（NHE）阻断剂）预处理的作用。15头Yorkshire-Duroc猪（37.1 +/- 4.2 kg）接受股-颈静脉旁路术和19 ℃下90分钟的深低温停循环。10只动物未接受治疗，而5只在冷却前接受5 mg/kg静脉注射cariporide。复温和关闭心肺转流后，将猪从麻醉中断奶并随访24小时。一个标准化的神经评分系统评估脑功能恢复。生化指标检测细胞损伤情况。在2只动物中进行了无循环停搏的对照研究，这些动物经历了类似的冷却和复温。在非缺血对照组和所有预处理动物中，神经功能恢复迅速且完全。相反，在24小时时，所有未处理的猪表现出意识模糊或昏迷水平，姿势异常，并且只有一只例外，不能坐或站。（评价中枢神经系统、运动和感觉功能、呼吸状况、意识水平和行为）为0 +/- 0（0 =正常，500例脑死亡），相比之下，未治疗组动物为124 59例。生化分析显示，未治疗组全身损伤的各项指标（包括共轭二烯（p < 0.05）、血清天冬氨酸氨基转移酶（p < 0.01）、肌酸激酶（p < 0.001）和内皮素-1（p < 0.001））均高于对照组。NHE功能改变实验性脑缺血再灌注损伤这些观察结果表明，缺血前的NHE抑制治疗可以改善在使用低温停循环的过程中经历脑缺血的成人和婴儿患者的神经保护。(C)2005年，美国胸外科医师协会（Society of Thoracic Surgeons）
Background. The effects of pretreatment with cariporide (HOE 642 Aventis Pharma, Strasbourg - Cedex, France), a Na+-H+ exchanger (NHE) blocker, were studied in a cerebral ischemia-reperfusion model of hypothermic arrest.Methods. Fifteen Yorkshire-Duroc pigs (37.1 +/- 4.2 kg) underwent femoral-jugular bypass and 90 minutes of deep hypothermic circulatory arrest at 19degreesC. Ten animals were untreated, whereas 5 received 5 mg/kg of intravenous cariporide before cooling. After rewarming and off cardiopulmonary bypass, the pigs were weaned from anesthesia and followed for 24 hours. A standardized neurologic scoring system assessed brain functional recovery. Biochemical markers were used to analyze cellular injury. Control studies without circulatory arrest were done in 2 animals that underwent similar cooling and rewarming.Results. Neurologic recovery was rapid and complete in the nonischemic controls and in all pretreated animals. Conversely, at 24 hours, all untreated pigs exhibited a cloudy or stuporous level of consciousness, abnormal positioning, and with only one exception, could not sit or stand. The gradation of neurologic score (evaluating central nervous system, motor and sensory functions, respiration condition, level of consciousness, and behavior) was 0 +/- 0 (0 = normal, 500 brain death) in the treated group, compared with 124 59 in the untreated animals. Biochemical analysis showed every variable of whole-body injury (including conjugated dienes (p < 0.05), serum aspartate amino transferase (p < 0.01), creatine kinase p < 0.001) and endothelin-1 (p < 0.001) to be higher in the untreated group.Conclusions. NHE function alters experimental brain ischemia-reperfusion damage. These observations imply that NHE inhibition therapy before ischemia may improve neurologic protection in adult and infant patients undergoing cerebral ischemia during procedures that use hypothermic circulatory arrest. (C) 2005 by The Society of Thoracic Surgeons.