Platelet activating factor antagonist enhances lung preservation

Platelet activating factor (PAF) is a potent phospholipid mediator of the immune and inflammatory responses, which causes physiologic effects similar to post-transplant pulmonary dysfunction. This study investigates the hypothesis that the use of a specific PAF antagonist (PAFA), BN 52021, in canine lung transplantation improves lung preservation. Twelve pairs of canines underwent left lung allotransplantation after pulmonary artery flushing with modified Euro-Collins (EC) solution (40 ml/kg). The experimental group (N = 6) received EC with BN 52021 (10 mg/kg). BN 52021 was administered to donors prior to harvest and to recipients prior to reperfusion. The preservation interval was 20 hr and the study period was 12 hr post-transplant. Differential pulmonary function and hemodynamics were monitored, comparing the transplanted left lung and the native right lung. Recipients were ventilated on 100% O₂. Administration of the platelet activating factor antagonist, BN 52021, was associated with improvement in transplant lung oxygenation, pulmonary vascular resistance, and compliance. At 12 hr, transplant lung pulmonary venous oxygen tension in the treatment group (EC + BN 52021) was 154 ± 21 mm Hg versus 87 ± 10 mm Hg in the control group (EC) (P < 0.05). Pulmonary vascular resistance of the transplant lung at 12 hr was 146 ± 24 Dynes·sec·cm^-5 in the EC + BN 52021 group as compared to 320 ± 51 Dynes·sec·cm^-5 in the EC group (P < 0.05). Dynamic pulmonary compliance of the transplant lung at 12 hr was 32 ± 2.9 ml/cm H₂O in the EC + BN 52021 group versus 13 ± 2.0 ml/cm H₂O in the EC group (P < 0.05). Total lung water for the EC group was 88.6 ± 14% versus 67.3 ± 11% for the EC + BN 52021 group (P < 0.05), as determined by proton magnetic resonance spectroscopy. From these data, we conclude that the specific PAFA, BN 52021, enhances lung preservation at 20 hr of ischemia in a canine model of left lung allotransplantation.