Xenotransplantation Surgery Section, Frontier Science Research Center, Kagoshima University, Kagoshima 890-8520, Japan.
J Thorac Cardiovasc Surg. 2010 Jun;139(6):1594-601. doi: 10.1016/j.jtcvs.2009.09.016. Epub 2009 Nov 11.
Carbon monoxide is produced endogenously as a by-product of heme catalysis and has been shown to reduce ischemia-reperfusion injury in a variety of organs in murine models. The aims of this translational research were to establish an in situ porcine lung model of warm ischemia-reperfusion injury and to evaluate the cytoprotective effects of low-dose inhaled carbon monoxide in this model.
Warm ischemia was induced for 90 minutes by clamping the left pulmonary artery and veins in 8 Clawn miniature swine (Japan Farm CLAWN Institute, Kagoshima, Japan). The left main bronchus was also dissected and reanastomosed just before reperfusion. Four animals were treated with inhaled carbon monoxide at a concentration of approximately 250 ppm throughout the procedure. Lung function and structure were serially accessed via lung biopsy, chest x-ray films, and blood gas analysis.
Carbon monoxide inhalation dramatically decreased the lung injury associated with ischemia and reperfusion. Two hours after reperfusion, the arterial oxygen tension of the carbon monoxide-treated group was 454 +/- 34 mm Hg, almost double the arterial oxygen tension of the control group (227 +/- 57 mm Hg). There were fewer pathologic changes seen on chest x-ray films and in biopsy samples from animals in the carbon monoxide-treated group. Animals in the carbon monoxide-treated group also had fewer inflammatory cell infiltrates and a markedly smaller increase in serum concentrations of the proinflammatory cytokines interleukin 1beta, interleukin 6, and high-mobility group box 1 after ischemia-reperfusion injury.
The perioperative administration of low-dose inhaled carbon monoxide decreases warm ischemia-reperfusion injury in lungs in miniature swine. This protective effect is mediated in part by the downregulation of proinflammatory mediators.
一氧化碳作为血红素催化的副产物在体内产生，已在多种动物模型中显示可减少缺血再灌注损伤。本转化研究的目的是建立猪原位肺缺血再灌注损伤模型，并评估低剂量吸入一氧化碳在该模型中的细胞保护作用。
通过夹闭 8 头克劳恩小型猪（日本农场克劳恩研究所，鹿儿岛，日本）的左肺动脉和静脉，诱导 90 分钟的热缺血。在再灌注前，还解剖并重新吻合左主支气管。4 只动物在整个过程中接受浓度约为 250ppm 的吸入一氧化碳治疗。通过肺活检、胸部 X 射线片和血气分析连续评估肺功能和结构。
一氧化碳吸入显著降低了与缺血和再灌注相关的肺损伤。再灌注后 2 小时，一氧化碳治疗组的动脉血氧分压为 454 +/- 34mmHg，几乎是对照组（227 +/- 57mmHg）的两倍。在一氧化碳治疗组的动物中，胸部 X 射线片和活检样本中可见的病理变化较少。与缺血再灌注损伤后，一氧化碳治疗组的动物也有较少的炎症细胞浸润，促炎细胞因子白细胞介素 1β、白细胞介素 6 和高迁移率族蛋白 1 的血清浓度明显升高。
围手术期给予低剂量吸入一氧化碳可减少小型猪肺部的热缺血再灌注损伤。这种保护作用部分是通过下调促炎介质介导的。
