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 perox idation of cell membrane polyunsaturated fatty acids, generating conju gated dienes (CD), is a toxicity of oxygen-derived free radicals. The CD structure in fatty acyl moieties was measured by high-pressure liqu id chromatography in samples of inferior pulmonary venous blood and pu lmonary tissue to assess reperfusion injury and oxygen-derived free ra dical-mediated damage in a canine model of left lung allotransplantati on. The cold ischemic preservation interval was 6 hours and the posttr ansplantation monitoring period was 6 hours. Twenty-eight size- and we ight-matched adult male dogs underwent left lung allotransplantation a nd were randomized to receive pulmonary artery flush of modified Euro- Collins (EC) (40 mL/kg) or University of Wisconsin (UW) (40 mL/kg) sol utions alone or with the addition of the platelet-activating factor an tagonist 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 we re obtained at baseline before transplantation and at 1, 2, 4, and 6 h ours after transplantation; tissue samples were obtained after euthana sia. 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 pu lmonary 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 wa s 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 fact or antagonist BN 52021 to either modified EC or UW pulmonary artery hu sh reduced the CD fraction as determined by high-pressure liquid chrom atography in pulmonary venous blood samples after transplantation in a canine model of single-lung allotransplantation, but did not change t he time of peak occurrence. Reductions in tissue CD fraction were seen in the BN 52021 study groups as compared with donor right lung and re cipient right lung controls. Peak CD serum levels occurred within 1 to 2 hours of reperfusion.