EXTENDED LUNG PRESERVATION WITH PLATELET-ACTIVATING FACTOR-ANTAGONISTTCV-309 IN COMBINATION WITH PROSTAGLANDIN E-1

Background: Ischemia-reperfusion injury is one: of the major problems in organ transplantation. The role of platelet-activating factor (PAF) in the pathophysiology of ischemia-reperfusion injury and the protect ive effect of a novel phospholipid PAF analog (TCV-309) alone and comb ined with prostaglandin E-1 (PGE(1)) is investigated in an extended (2 0 hours) ex vivo lung preservation, Methods: Forty-two swine were divi ded into three groups. Group A was the control. In groups B and C, the effect of PAF was blocked with TCV-309 administered 1 hour before cro ss-clamping for donor and recipient. Group C received PGE, 50 mu g bol us in the donor pulmonary plegia, and the recipients received a 50 mu g bolus plus 0.003 mu g/kg/min infusion at; the time of implantation, Donor lungs were perfused with cold modified Collins solution and main tained in hypothermic storage (4 degrees C) for 20 hours, Hemodynamics , lung mechanics, gas exchange, and biochemistry were assessed before transplantation (donor) and at 30 minutes and 24 hours after reperfusi on (recipient), At 24 hours after reperfusion, the histopathologic con dition of transplanted lungs was evaluated. Results: Radioimmunoassay demonstrated a significant (p < 0.001) increase in the production of P AF and TXB2 in transplanted lungs at 24 hours after transplantation fo r group A only, Hemodynamics, gas-exchange parameters, and lung compli ance were significantly (p < 0.05) better after transplantation:or gro ups B and C. Wet lung weight was significantly less (p < 0.05) for gro up C, Semiquantitative morphometric analysis demonstrated the highest degree of damage for,stoup A compared with groups B and C. A strong co rrelation (r(2) = 70) between lung weight and histologic injury scores was observed among groups. Conclusions: This study suggests that PAF is responsible in part for the deleterious effects of ischemia and rep erfusion, that PAF-antagonist TCV-309 protects lungs from extended (20 hours) ischemic injury, and that PGE(1) seems to have an additional b eneficial effect.