Kim J D, Baker C J, Roberts R F, Darbinian S H, Marcus K A, Quardt S M, Starnes V A, Barr M L
Department of Cardiothoracic Surgery, University of Southern California and Childrens Hospital, Los Angeles 90033, USA.
Ann Thorac Surg. 2000 Aug;70(2):423-8. doi: 10.1016/s0003-4975(00)01405-3.
Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood.
Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood.
After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV.
Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.
缺血再灌注损伤涉及自由基生成、多形核中性粒细胞趋化/脱颗粒，以及蛋白水解酶、补体成分、凝血因子和细胞因子的产生。活化的多形核中性粒细胞、内皮细胞和巨噬细胞产生血小板活化因子，这进一步促进了这些炎症反应。最近克隆的血浆形式的血小板活化因子乙酰水解酶（PAF-AH）通过降解血小板活化因子表现出抗炎作用。我们通过将PAF-AH添加到冲洗液或再灌注血液中，在离体灌注大鼠肺模型中评估其作用。
分离大鼠肺，用EuroCollins（EC）或威斯康星大学（UW）溶液冲洗，在4℃下保存6或12小时，然后使用交叉循环的同基因支持大鼠进行再灌注。在再灌注期间，计算氧合、顺应性和毛细血管滤过系数。研究分为四组；I组（对照组）未添加PAF-AH，II组将PAF-AH添加到冲洗液中，III组将PAF-AH添加到再灌注血液中，IV组将PAF-AH添加到冲洗液和再灌注血液中。
保存6小时后，IV组中EC的氧合、顺应性和毛细血管滤过系数显著改善。对于UW，IV组氧合改善，而II、III和IV组顺应性改善。保存12小时后，IV组中EC的顺应性改善，III和IV组的毛细血管滤过系数改善。对于UW，II和IV组氧合和顺应性改善，而IV组毛细血管滤过系数改善。
将PAF-AH添加到细胞内器官保存溶液和血液再灌注液中可显著改善再灌注后的氧合和顺应性，并降低肺毛细血管通透性。
