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

无心跳供体大鼠肺移植中前列环素的支气管内给药

• 批准号: 10671245
• 负责人: WATANABE Yoh
• 金额: $ 1.98万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671245/
• 关键词: Lung transplantation; Lung preservation; Non-heart-beating donor; Prostaglandin E1; cAMP; PGE1; 肺再灌流障害; 脳死肺; 心停止肺; プロスタグランディン

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".

背景：在非心脏供体肺移植（NHBD）中，死后热缺血加重了肺缺血再灌注损伤，我们假设支气管内给药前列腺素E1 （PGE1）可以减轻缺血再灌注损伤，改善肺移植的存活率。方法：就地热缺血60分钟后，从非心脏供体中冲洗取出大鼠双肺块，保存2小时。用t型管将供体肺块的肺动脉主动脉和左心房与同型受体的左肺动脉静脉相连。心脏跳动供者作为HBD对照组（1组），未治疗的NHBD对照组（2组）。第3组在原位热缺血（NHBD缺血PGE1）时支气管内给药PGE1 （2 μg/0.2 ml）。第4组在再灌注时给予PGE1 (2 μg/0.2 ml) （NHBD再灌注PGE1）。获得了移植物肺血管阻力、血气等一系列测量结果。再灌注60分钟后测定肺组织环AMP、髓过氧化物酶及干湿比。结果：NHBD对照组发生严重IR损伤。与NHBD对照组相比，在热缺血（NHBD缺血PGE1）期间给予PGE1显著降低PVR，改善PO2。再灌注时给予PGE1 （NHBD再灌注PGE1）并没有减轻IR损伤。与土地2组相比，III组肺cAMP水平显著升高。给药PGE1（3组和4组）没有降低肺MPO。1、3组移植体增重明显高于2、4组。结论：这些数据表明，在热缺血期间支气管内给药PGE1有利于保存NHBD肺移植功能。这可能是“细胞保护作用”的结果。

项目成果

川口雅彦: "吸入療法による肺虚血再灌流障害の予防に関する実験的研究"金沢大学十全医学会雑誌. 108・6. 687-694 (1999)

川口正彦：“吸入疗法预防肺缺血再灌注损伤的实验研究”金泽大学十善医学会杂志108・6（1999）。