Intrabronchial administration of prostacycline in rat lung transplantation from Non-Heart-Beating Donors

背景：在非心脏跳动供体（NHBD）肺移植中，死后热缺血加重了肺的缺血再灌注损伤。我们假设支气管内给予前列腺素E1（PGE 1）可减轻缺血再灌注损伤，改善肺移植物的存活率。大鼠双肺组织块在原位热缺血60分钟后，从无心跳供体处冲洗并取出，然后保存2小时。供体肺块的主肺动脉和左心房通过T形管与同系受体的左肺动脉和左肺静脉相连。第1组为正常对照组，第2组为正常对照组。第3组在原位热缺血（NHBD ischemia，NHBD ischemia）时支气管内注射PGE_1（2 μg/0.2ml）。第4组在再灌注过程中给予PGE 1（2 μg/0.2ml）（NHBD再灌注PGE 1）。测定移植肺血管阻力、血气指标。结果：NHBD组大鼠肺组织缺血再灌注60分钟后出现严重的缺血再灌注损伤。与NHBD对照组相比，NHBD缺血期给予PGE 1可显著降低PVR，改善PO 2。再灌注期间给予PGE 1（NHBD再灌注PGE 1）不能减轻IR损伤。肺组织cAMP水平Ⅲ组明显高于Ⅱ组。给予PGE 1（3组和4组）不降低肺MPO。结论：支气管内注射PGE 1有利于NHBD肺移植物功能的保护。这可能是“细胞保护作用”的结果。

Backgroud : In lung transplantation using Non-Heart-Beating donors(NHBD), the postmortem period of warm ischemia exacerbates lung ischemia-reperfusion injury, We hypothesized that intrabronchial administ rat ion of Prostaglandin E1 (PGE1) would reduce ischemia-reperfusion injury, and ameliorate the viability of the lung graft.Method : Rat double-lung blocks were flushed and havested from non-heart-beating donors after 60 minutes of in situ warm ischemia, then stored for 2 hours. The main pulmonary artery and left atrium of donor lung blocks were connected to the left pulmonary artery and veins of a syngeneic recipient using T-shaped tubes. Heart-Beating-Donors aseved as HBD control (group 1) and untreated NHBD as NHBD control (group 2). In group 3, the intrabronchial administration of PGE1 (2 μg/0.2 ml)was perfomed during in situ warm ischemia (NHBD ischemia PGE1) . In group 4, PGE1 (2 μg/0.2 ml) was administered during reperfusion (NHBD reperfuision PGE1). Serial measurements of graft pulmonary vascular resistance, blood gases were obtained. Lung tissue cyclic AMP and myeloperoxidase, and wet/dry ratio were measured after 60 minutes reperfusion.Results : Severe IR injury ocurred in NHBD control. Administration of PGE1 during warm ischemia (NHBD ischemia PGE1) significantly decreased PVR, and improved PO2 compared with NHBD control. Administration of PGE1 during reperfusion (NHBD reperfuision PGE1) did not attenuate IR injury. The lung cAMP level in group III was significantly high compared with those of group land 2. Administration of PGE1 (goup 3 and 4) did not decreased lung MPO. grafts in guoup 1 and 3 had significantlu more weight gain compared those of group 2 and 4.Conclusion : These data suggested that intrabronchial administration of PGE1 during warm ischemia is advantageous for preservation of graft function in lungs harvested from NHBD. This is likely the result of "cytoprotective effect".