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

肺或心肺移植后移植物衰竭通常是由于移植肺缺血再灌注损伤引起的肺水肿引起的。众所周知，中性粒细胞产生的氧自由基在缺血器官中造成再灌注损伤。我们研究了犬肺和心肺同种异体移植后肺再灌注损伤的发生情况。为了评价抗氧化剂如谷胱甘肽、抗坏血酸（维生素C）、维生素E、超氧化物歧化酶（SOD）和辅酶Q10的功效，用含有这些抗氧化剂之一的Euro-Collins溶液冲洗左肺，然后在该肺中进行肺门钳夹。在开放夹闭前静脉给予抗坏血酸和α-生育酚。在用抗氧化剂处理的肺中，氧自由基的产生减少，氧合与未处理的肺相当。因此，输注这些抗氧化剂可能有助于预防肺动脉高压。 ...更多信息 移植后无水肿.采用保存液冲洗的方法，将犬左肺在4 ℃下缺血冷藏24小时，然后用全血或去白细胞血进行再灌注。在用Euro-Collins溶液冲洗的肺中，用去白细胞血液再灌注后的肺水量低于全血。另一方面，在用UW溶液（含有谷胱甘肽和别嘌呤醇等抗氧化剂）冲洗的肺中，全血与去白细胞血液再灌注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缺血再灌注损伤发生的重要因素之一，缺血肺再灌注前灌注去白细胞血可有效预防或减轻肺水肿.我们成功地进行了犬同种异体肺移植后，冷处理8小时，在此期间，肺冲洗和保存的Euro-Collins液含有抗氧化剂，如谷胱甘肽，别嘌呤和SOD。此外，用UW液在4 ℃保存24小时的犬肺同种异体移植也获得成功。但即使使用UW液冲洗和保存移植物，犬心肺块冷保存时间的安全限度也为4 h.为了评估UW溶液中的最佳钾浓度，使用离体犬肺灌注模型评估再灌注后的肺水量。用含钾120、30或4 mEq/L的UW溶液冲洗犬左肺，并在4 ℃下保存24小时，然后用全血再灌注肺120分钟。在用含30 mEq/L钾的UW溶液冲洗的肺中，肺水量最低，表明这是UW溶液中保存心肺移植物的最佳钾浓度。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） ）。