| Co-Investigator(Kenkyū-buntansha) |
ITOYANAGI Noriake Nagasaki university School of Medicine, 医学部, 医員
AKAMINE Sinji Nagasaki university School of Medicine, 医学部, 医員
AYABE Hiroyoshi Nagasaki university School of Medicine Assistant Professor, 医学部, 助教授 (60128147)
TOMITA Masao Nagasaki university School of Medicine Professor, 医学部, 教授 (70039808)
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| Research Abstract |
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
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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
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