Survival and graft function in a large animal lung transplant model after 30 h preservation and substitution of the nitric oxide pathway

Objective: Substitution of the nitric-oxide- (NO-) pathway improves early g raft function following lung transplantation. We previously demonstrated th at 8-Br-cGMP (second messenger of NO) to the flush solution and tetrahydrob iopterin (BH4, coenzyme of NO synthase) given as additive during reperfusio n improve post-transplant graft function. In the present study, the combine d treatment with B-Br-cGMP and BH4 was evaluated. Methods: Unilateral left lung transplantation was performed in weight matched outbred pigs (24-31 kg ). In group I, grafts were preserved for 30 h (n=5). 8-Br-cGMP (1 mg/kg) wa s added to the flush solution (Perfadex(TM), 1.5 1, 1 degreesC) and BH4 (10 mg/kg/h) was given to the recipient for 5 h after reperfusion. In group II , lungs were transplanted after a preservation time of 30 h (n=3) and prost aglandin E-1 (250 g) was given into the pulmonary artery (PA) prior to flus h. In all recipients 1 h after reperfusion the contralateral right PA and b ronchus were ligated to assess graft function only. Survival time after rep erfusion, extravascular lung water index (EVLWI), hemodynamic variables, an d gas exchange (PaO2) were assessed during a 12 h observation period. Resul ts: All recipients in group I survived the 12 h assessment, whereas none of the group II animals survived more than 4 h after reperfusion with a rapid increase of EVLWI up to 24.8 +/-6.7 ml/kg. In contrast, in group I EVLWI r eached up to 8.9 +/-1.5 ml/kg and returned to nearly normal levels at 12 h (6.1 +/-0.8 ml/kg). In two animals of group I the gas exchange deteriorated slightly. The other three animals showed normal arterial oxygenation over the entire observation time. Conclusion: Our data indicate that the combine d substitution of the NO pathway during preservation and reperfusion reduce s ischemia/reperfusion injury substantially and that this treatment even al lows lung transplantation after 30 h preservation in this model. (C) 2001 E lsevier Science B.V. All rights reserved.