Donor and recipient treatment with the Lazaroid U-74006F do not improve post-transplant lung function in swine

Objective: U-74006F is the only Lazaroid which is currently in clinical use . A number of experimental studies demonstrate that Lazaroids reduce ischem ia/reperfusion injury in various organ systems. We evaluated the effect of U-74006F on reperfusion injury in a large animal model of lung allo-transpl antation. Methods: Two different treatment modalities were evaluated and co mpared with corresponding control groups. Unilateral left lung transplantat ion was performed in 21 weight-matched pigs (24-31 kg). Donor lungs were fl ushed with 1.5 l cold (1 degrees C) LPD solution and preserved for 20 h. In group I (n = 5), donor animals were pretreated with U-74006F (10 mg/kg i.v .) 20 min before harvest. In addition U-74006F was added to the flush solut ion (10 mg/l). In group III (n = 6), the Lazaroid was given to the donor be fore flush and to the recipient before reperfusion (3 mg/kg i.v.), Group II and IV (n = 5) served as control. One hour after reperfusion, the recipien t contralateral right pulmonary artery and bronchus were ligated to assess graft function only. Extravascular lung water index (EVLWI), mean pulmonary artery pressure, cardiac output, and gas exchange were assessed during a 5 h observation period. Lipid peroxidation (TBARS) and neutrophil migration (MPO activity) were measured at the end of the assessment in lung allograft tissue. Results: A significant change of TEARS concentration was shown in group III (group III 78.7 +/- 4.6 pmol/g vs. group IV 120.8 +/- 7.2 pmol/g (P = 0.0065) normal lung tissue 41.3 +/- 4.2 pmol/g). MPO activity was redu ced in group III 3.74 +/- 0.25 Delta OD/mg per min vs. group IV 4.97 +/- 0. 26 Delta OD/mg per min (P = 0.027), normal lung tissue 1.04 +/- 0.27 Delta OD/mg per min). Pulmonary hemodynamics and gas exchange after reperfusion d id not differ between groups. In group I and III, a tendency towards a redu ced EVLWI was noted. Conclusion: We conclude that combined treatment of don or and recipient with U-74006F reduces free radical mediated injury in the allograft. However, this intervention did not result in a significant reduc tion of post-transplant lung edema or improvement of pulmonary hemodynamics . Donor pretreatment alone did not improve lung allograft reperfusion injur y. These results indicate that the benefit of U-74006F is too small to cons ider clinical application in lung transplantation. (C) 1999 Elsevier Scienc e B.V. All rights reserved.