REDUCTION OF CONJUGATED DIENES IN LUNG TRANSPLANTATION - EFFECT OF BN-52021

Oxygen-derived free radicals have been identified as the mediators of tissue injury during reperfusion in organ transplantation, Lipid peroxidation of cell membrane polyunsaturated fatty acids, generating conjugated dienes (CD), is a toxicity of oxygen-derived free radicals. The CD structure in fatty acyl moieties was measured by high-pressure liquid chromatography in samples of inferior pulmonary venous blood and pulmonary tissue to assess reperfusion injury and oxygen-derived free radical-mediated damage in a canine model of left lung allotransplantation. The cold ischemic preservation interval was 6 hours and the posttransplantation monitoring period was 6 hours. Twenty-eight size- and weight-matched adult male dogs underwent left lung allotransplantation and were randomized to receive pulmonary artery flush of modified Euro-Collins (EC) (40 mL/kg) or University of Wisconsin (UW) (40 mL/kg) solutions alone or with the addition of the platelet-activating factor antagonist BN 52021 (10 mg/kg). When employed, BN 52021 was administered to donors 30 minutes before harvest and recipients 30 minutes before reperfusion. Left and right inferior pulmonary venous blood samples were obtained at baseline before transplantation and at 1, 2, 4, and 6 hours after transplantation; tissue samples were obtained after euthanasia. Serum and tissue CD levels are expressed as mean fraction of the total hydroperoxide sample +/- standard error of the mean. At 6 hours after transplantation, the EC group's (n = 7) CD fraction was 0.28 +/- 0.03, whereas that of the EC + BN 52021 group (n = 7) was 0.12 +/- 0.03 (p < 0.05). At 6 hours after transplantation, left lung inferior pulmonary venous serum CD fraction for the UW group (n = 7) was 0.39 +/- 0.05, whereas that of the UW + BN 52021 group (n = 7) was 0.22 +/- 0.03 (p < 0.05). Transplant lung tissue CD fraction for the EC group was 0.30 +/- 0.03, whereas that of the EC + BN 52021 group was 0.21 +/- 0.03 (p < 0.05). Transplant lung tissue CD fraction for the UW group was 0.32 +/- 0.02, whereas that of the UW + BN 52021 group was 0.20 +/- 0.03 (p < 0.05). The addition of the specific platelet-activating factor antagonist BN 52021 to either modified EC or UW pulmonary artery hush reduced the CD fraction as determined by high-pressure liquid chromatography in pulmonary venous blood samples after transplantation in a canine model of single-lung allotransplantation, but did not change the time of peak occurrence. Reductions in tissue CD fraction were seen in the BN 52021 study groups as compared with donor right lung and recipient right lung controls. Peak CD serum levels occurred within 1 to 2 hours of reperfusion.