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

肺或心肺移植后移植物衰竭常由移植肺缺血再灌注损伤引起的肺水肿引起。众所周知，中性粒细胞产生的氧自由基可造成缺血器官的再灌注损伤。我们研究了犬肺和心肺同种异体移植后肺再灌注损伤的预估。为了评估抗氧化剂如谷胱甘肽、抗坏血酸（维生素C）、α -酚（维生素E）、超氧化物歧化酶（SOD）和辅酶q10的疗效，用含有其中一种抗氧化剂的Euro-Collins溶液冲洗左肺，然后对左肺进行肺门夹紧。在去钳前静脉注射抗坏血酸和α -生育酚。在肺部使用抗氧化剂治疗后，氧自由基的产生减少，氧合作用与未治疗的肺部相当。因此，输注这些抗氧化剂可能有助于预防移植后肺水肿。采用保鲜液冲洗技术对犬左肺进行4‰C低温缺血冷藏24 h，全血或去白细胞血对肺进行再灌注。用Euro-Collins液冲洗肺时，去白细胞血再灌注后肺水量低于全血。另一方面，用含有谷胱甘肽和别嘌呤醇等抗氧化剂的UW溶液冲洗肺时，全血和去白细胞血再灌注后肺水量无差异。结果提示，由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，缺血肺再循环前灌注去白细胞血的酸能有效预防或减轻肺水肿。我们成功地移植了狗肺，在冷置8小时后，用含有谷胱甘肽、别嘌呤和SOD等抗氧化剂的Euro-Collins溶液冲洗和保存肺。此外，用UW溶液在4‰C下保存24小时的狗肺冲洗酸移植也取得了成功。然而，即使使用UW溶液冲洗和保存移植物，用于移植的犬心肺块冷保存时间的安全极限也是4小时。为了评估UW溶液中最佳钾浓度，采用离体犬肺灌注模型评估再灌注后肺水量。用含钾120、30、4 mEq/L的UW溶液冲洗犬左肺，4 C保存24小时，然后全血再灌注120分钟。30meq /L含钾UW溶液冲洗肺时肺水体积最小，提示这是保存心肺移植物的最佳UW溶液钾浓度。少

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