Experimental study on protection of pulmonary edema after lung and heart-lung transplantation

肺及心肺移植术后肺水肿保护作用的实验研究

• 批准号: 01570787
• 负责人: KAWAHARA Katsunobu
• 金额: $ 1.34万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570787/
• 关键词: Lung transplantation; Heart-lung transplantation; Oxygen radicals production; University of Wisconsin solution; Superoxide dismutase; alpha-tocopherol; Aserbic acid; glutathione; 心肺保存; 心肺同時移植; 単純浸漬冷却保存; 肺水腫; 肺血管外水分量; 肺血管抵抗; 組織過酸化脂質; UWH; S

Graft failure after lung or heart-lung transplantation is often caused by pulmonary edema resulting from ischemic reperfusion injury of the transplanted lung. It is well known that oxygen free radicals produced by neutrophils create reperfusion injury in iscliemic organs. We studied the prevelition of pulmonary reperfusion injury after canine lung and heart-lung allotransplantation.1. To evaluate the efficacy of antioxidants such as glutathione, ascorbic acid (vitamin C), alphatocopherol (vitamin E), superoxide dismutase (SOD), and CoQ10, the left lung was flushed with Euro-Collins solution containing one of these antioxidants, and then a hilar clamp was performed in this lung. Ascorbic acid and alpha-tocopherol were administered intravenously prior to declamping. In the lungs treated with antioxidants, the production of oxygen free radicals decreased, and oxygenation was comparable to that in untreated lungs. Therefore, infusion of these antioxidants may be useful for preventing pulmo … More nary edema after transplantation.2. Ischemic cold storage of canine left lungs at 4ﾟC for 24 hours was performed using a technique of flushing with preservative solution, and the lungs were reperfused with whole blood or leukocytedepleted blood. In the lungs flushed with Euro-Collins Solution, the lung water volume after reperfusion with leukocyte-depleted blood was lower than that with whole blood. On the other hand, in the lungs flushed with UW solution, which contained antioxidants such as glutathione and allopurinol, there was no difference between the lung water volume after reperfusion with whole vs leukocytedepleted blood. Results suggested that oxygen free radicals originating from neutrophils are one of the most important factors in the occurrence of ischemic reperfusion injury in grafted lungs, acid that perfusion with leukocyte-depleted blood prior to recirculation of the iscliemic lung is effective in preventing or alleviating pulmonary edema.3. We successfully allotransplaned canine lungs after cold strage for 8 hours during which the lungs were flushed and preserved with Euro-Collins solution containing antioxidants such as glutathione, allopurinal, and SOD. Furthermore, allotransplantation of canine lungs flushed acid preserved with UW solution at 4ﾟC for 24 hours was also successful. However, the safety limit of the cold preservation time of a canine heart-lung block for transplantation was 4 hours even when using the UW solution for flushing and preserving the graft.4. To evaluate the optimum potassium concentration in the UW solution, the lung water volume after reperfusion was evaluated using an isolated canine lung perfusion model. Canine left lungs were flushed with UW solution containing potassium at 120, 30, or 4 mEq/L, and preserved at 4ﾟC for 24 hours, then the lungs were reperfused with whole blood for 120 minutes. The lung water volume was lowest in the lungs flushed with UW solution containing potassium at 30 mEq/L, suggesting that this is the optimum potassium concentration in UW solution for preserving heart-lung grafts. Less

肺或心肺联合移植后的移植物衰竭通常是由于移植肺的缺血再灌注损伤引起的肺水肿所致。众所周知，中性粒细胞产生的氧自由基会造成缺血器官的再灌注损伤。我们研究了犬肺和同种异体心肺移植后肺再灌注损伤的发生。为评价谷胱甘肽、抗坏血酸(维生素C)、α-苯酚(维生素E)、超氧化物歧化酶(SOD)和辅酶Q10等抗氧化剂的疗效，用含有这些抗氧化剂之一的Euro-Collins液冲洗左肺，然后对左肺进行肺门钳夹。解压前静脉注射抗坏血酸和α-生育酚。在接受抗氧化剂治疗的肺中，氧自由基的产生减少，氧合作用与未治疗的肺相当。因此，注入这些抗氧化剂可能有助于预防Pulmo…。结论：1.移植后神经水肿明显增多。犬左肺在4ﾟC条件下，采用保存液冲洗技术进行缺血冷藏24小时，再用全血或去白细胞血液进行肺再灌流。在用Euro-Collins液冲洗的肺中，去白细胞血液再灌流后的肺水量低于全血灌流。另一方面，在含有谷胱甘肽和别嘌醇等抗氧化剂的UW液冲洗的肺中，全血再灌流后的肺水量与去白细胞后的肺水量没有差异。结果提示，中性粒细胞产生的氧自由基是移植肺发生缺血再灌注损伤的重要因素之一，缺血肺再循环前用去白细胞血液灌流是预防或减轻肺水肿的有效方法。我们成功地进行了8小时的犬肺移植，在此期间，肺被冲洗并用含有抗氧化剂的Euro-Collins液保存，这些抗氧化剂包括谷胱甘肽、别尿酸和超氧化物歧化酶。此外，用UW液在4ﾟC保存24小时的同种异体犬肺也是成功的。然而，即使使用UW液冲洗和保存移植物，犬移植心肺块的冷保存时间的安全限度也是4小时。为评价UW液中钾离子的最佳浓度，采用犬离体肺灌流模型评价再灌流后的肺水量。犬左肺分别用含钾120、30、4mEq/L的UW液冲洗，在4ﾟC保存24小时，然后用全血再灌流120分钟。含钾UW液灌洗肺的肺水量最低，为30mEq/L，提示这是保存心肺移植物的最佳UW液钾浓度。较少

项目成果

碇 秀樹: "イヌ摘出左肺潅流モデルによる保存液の評価" 第6回肺および心肺移植研究会.

Hideki Ikari：“使用犬离体左肺灌注模型评估保存液”第6届肺和心肺移植研究组。

K.Kawahara: "Graft function associated with oxygen free radicals immediately after transplantation" Acta Medica Nagasakinsia. 35. 225-227 (1990)

K.Kawahara：“移植后立即与氧自由基相关的移植功能”Acta Medica Nagasakinsia。

Katsunobu Kawahara: "Twentyーfourーhour canine lung preservation using UW solution" Transplantation. 51. 584-587 (1991)

Katsunobu Kawahara：“使用 UW 溶液进行二十四小时犬肺保存”移植。 51. 584-587 (1991)

小林 誠博,川原 克信,高橋 孝郎,赤嶺 晋治,糸柳 則昭,村田 謙,綾部 公懿,富田 正雄: "Low potassium UW液による24時間肺保存の実験的検討" 日本呼吸器外科学会雑誌. 5. 324 (1991)

Masahiro Kobayashi、Katsunobu Kawahara、Takao Takahashi、Shinji Akamine、Noriaki Itoyanagi、Ken Murata、Koki Ayabe、Masao Tomita：“使用低钾 UW 溶液进行 24 小时肺保存的实验研究”日本呼吸外科学会杂志 5。 324 (1991)

村岡 昌司,川原 克信,高橋 孝郎,山本 聡,中村 昭博,田川 務,綾部 公懿,富田 正雄: "CMH solutionによる24時間冷却保存肺の機能に関する実験的検討" 第19回臓器保存研究会(H4.3.23).

Masashi Muraoka、Katsunobu Kawahara、Takao Takahashi、Satoshi Yamamoto、Akihiro Nakamura、Tsutomu Takawa、Koki Ayabe、Masao Tomita：“利用 CMH 溶液进行 24 小时冷藏肺功能的实验研究”第 19 期器官保存研究组（H4.3.23） ）。