Platelet activating factor acetylhydrolase decreases lung reperfusion injury

Background. Ischemia-reperfusion injury involves free radical production, p olymorphonuclear neutrophil chemotaxis/degranulation, and production of pro teolytic enzymes, complement components, coagulation factors, and cytokines . Activated polymorphonuclear neutrophils, endothelial cells, and macrophag es produce platelet activating factor, which further promotes these inflamm atory reactions. The recently cloned plasma form of platelet activating fac tor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degra ding platelet activating factor. We evaluated the effects of PAF-AH in an i solated perfused rat lung model by adding it to the hush solutions or to th e reperfusion blood. Methods. Rat lungs were isolated, flushed with EuroCollins (EC) or Universi ty of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfu sion, oxygenation, compliance, and capillary filtration coefficient were ca lculated. 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 PA F-AH added to reperfusion blood, and group IV had PAF-AH added to both flus h solution and reperfusion blood. Results. After 6 hours of storage, oxygenation, compliance, and capillary f iltration coefficient significantly improved for EC in group IV. For UW, ox ygenation improved in group IV whereas compliance improved in groups II, II I, and IV. After 12 hours of storage, compliance improved for EC in group I V and capillary filtration coefficient improved in groups III and IV. For U W, oxygenation and compliance improved in groups II and IV, whereas capilla ry filtration coefficient improved in group IV. Conclusions. Addition of PAF-AH to intracellular organ preservation solutio ns and to the blood reperfusate significantly improves postreperfusion oxyg enation and compliance, and reduces lung capillary permeability. (C) 2000 b y The Society of Thoracic Surgeons.