Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs
Isoflurane inhalation after circulatory arrest protects against warm ischemia reperfusion injury of the lungs
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DOI：
10.1097/01.tp.0000237207.73439.2e
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发表时间：
2006-11-15
期刊：
影响因子：
6.2
通讯作者：
Bando, Toru
中科院分区：
文献类型：
--
作者：
Fujinaga, Takuji;Nakamura, Takayuki;Bando, Toru
背景。非心脏供体有望改善器官移植供体短缺的状况。预防循环骤停后的热缺血损伤是必须研究的问题。本研究探讨了热缺血时吸入异氟醚是否能减轻肺缺血再灌注损伤（IRI）。采用离体灌注大鼠肺模型。将大鼠分为4组：无缺血组；缺血-1最小肺泡浓度（MAC） iso组（空气和1.38%异氟烷通气）；缺血- 3mac iso组（空气和4.2%异氟烷通气）；缺血无治疗组（仅空气通气）。实验一肺缺血50 min， 37℃，再灌注后测定肺生理功能。实验二测定热缺血后线粒体控制率（RCR）、线粒体细胞色素c释放量和caspase活性。实验一，缺血- 1mac - iso组肺功能明显优于缺血-无治疗组。1MAC和3MAC异氟醚之间没有剂量依赖效应。实验二，缺血- 1mac iso组RCR显著大于缺血-无处理组。与未缺血组相比，缺血- 1mac iso组细胞色素c释放和caspase-9活性显著降低。吸入异氟醚可通过线粒体的保护减弱热IRI。本研究结果提示，循环停搏后吸入异氟醚是一种简单有效的肺热缺血保护方法。
Background. Non-heart-beating donors are expected to ameliorate shortages of donors for organ transplantation. The issue of preventing warm ischemic injury after circulatory arrest must be investigated. In the current study, we investigated whether isoflurane inhalation during warm ischemia could attenuate ischemia reperfusion injury (IRI) of the lung.Methods. An isolated perfused rat lung model was used. The rats were allocated into four groups: the no ischemia group; the ischemia-1 minimum alveolar concentration (MAC) iso group (ventilation with air and 1.38% isoflurane); the Ischemia-3MAC iso group (ventilation with air and 4.2% isoflurane); and the Ischemia-no treatment group (ventilation with only air). Lungs were subjected to 50 min of ischemia at 37 degrees C. Physiological lung functions were measured after reperfusion in experiment one. Mitochondrial control ratio (RCR), cytochrome-c release from mitochondria, and caspase activities just after warm ischemia were measured in experiment two.Results. Pulmonary functions in the Ischemia-1MAC iso group were significantly greater than those in the Ischemia-no treatment group for experiment one. There were no dose-dependent effects between 1MAC and 3MAC isoflurane. In experiment two, RCR in the Ischemia-1MAC iso group was significantly greater than that in the Ischemia-no treatment group. Cytochrome-c release and caspase-9 activity in the Ischemia-1MAC iso group were significantly decreased compared to those in the Ischemia-no treatment group.Conclusions. Isoflurane inhalation attenuates warm IRI with the protection of mitochondria. Our results suggest that isoflurane inhalation after circulatory arrest can be a simple and effective method to protect the lung against warm ischemia.