8-Br-cyclic GMP given during reperfusion improves posttransplant lung edema and free radical injury

Substitution of the NO-pathway reduces ischemia/reperfusion injury followin g lung transplantation. 8-Br-cGMP is a membrane permeable analogue of cGMP, the second messenger of NO, In this study the effect of continuous adminis tration of 8-Br-cGMP on early graft function was evaluated. Methods: Unilateral left lung transplantation was performed in 10 weight-ma tched pigs (23-30 kg). Donor lungs were flushed with 151 cold (1 degrees C) LPD solution and preserved for 20 hours. In Group I (n = 5), 8-Br-cGMP (0. 2 mg/kg/h) was given continuously over the entire observation time starting 15 min before reperfusion. Group II served as control, no 8-Br-cGMP was ad ministered. In both groups, 259 mu g PGE, was injected into the pulmonary a rtery (PA) before flush. One hour after reperfusion the recipients contrala teral right PA and bronchus were ligated to assess isolated graft function only. Extravascular lung water index (EVLWI), pulmonary vascular resistance , mean PA pressure, mean systemic arterial pressure and gas exchange were a ssessed during a 5-hour observation period. Lipid peroxidation as indicator for free radical mediated injury and neutrophil migration to the allograft were measured at the end of the assessment. Results: EVLWI was significantly reduced in animals treated with 8-Br-cGMP (overall difference P = 0.024) with a peak 2 hours after reperfusion (Group I, 8.2 +/- 0.3 mg/ml vs Group II, 10.1 +/- 0.6 mg/ml; P = 0.039). Also in Group I the free radical mediated tissue injury was significantly lower whe n compared to Group II (Group I, 61.8 +/- 12.3 pmol/g vs Group II, 120.7 +/ - 7.2 pmol/g; P = 0.006). A tendency towards a reduced neutrophil migration after 8-Br-cGMP infusion was shown; however, the changes in comparison to the control animals were not statistically significant (Group I, 1.0 +/- 0. 2 Delta OD/mg/min vs Group II, 1.7 +/- 0.3 Delta OD/mg/min; P = 0.13). Pulm onary- and systemic hemodynamics, and allograft gas exchange did not differ between groups. Conclusions: The results indicate that substitution of the NO pathway by ad ministration of the second messenger cGMP at the time of reperfusion improv es post-transplant lung allograft function.