8-Br-cGMP is superior to prostaglandin E-1 for lung preservation

Background. Substitution of the nitric oxide (NO) pathway reduces ischemia/ reperfusion injury after lung transplantation. 8-Br-cGMP is a membrane-perm eable analogue of cGMP, the second messenger of NO. In this study, we evalu ated the effect of administration of 8-Br-cGMP in the flush solution on ear ly graft function. Methods. Unilateral left lung transplantation was performed in 10 weight-ma tched pairs of outbred pigs (24 to 31 kg). Donor lungs were flushed with 1. 5 L cold (1 degrees C) low potassium dextrane (LPD) solution and preserved far 20 hours. In group I (n = 5), 8-Br-cGMP (1 mg/kg) was added to the flus h solution. In group II (n = 5), 8 mu g/kg prostaglandin E-1 (PGE(1)) was i njected into the pulmonary artery (PA) before flush. One hour after reperfu sion, the recipients' contralateral right PA and bronchus were ligated to a ssess graft function only, cGMP levels in the PA and pulmonary vein were me asured. Extravascular lung water index (EVLWI), pulmonary vascular resistan ce, mean PA pressure, and gas exchange (PaO2) were assessed during a 5-hour observation period. Lipid peroxidation (thiobarbituric acid-reactive subst ance) and neutrophil migration to the allograft (myeloperoxidase activity) were measured at the end of the assessment. Results. In group I, a significant reduction of EVLWI (group I, 6.7 +/- 1.0 mL/kg vs group II, 10.1 +/- 0.6 ml/kg after 2 hours of reperfusion; p = 0. 022), TEARS (group I, 65.6 +/- 10.0 pmol/g vs group II, 120.8 +/- 7.2 pmol/ g, p = 0.0039), and MPO activity (group I, 0.8 +/- 0.1 change in optical de nsity, (Delta OD)/mg/min vs group II, 1.7 +/- 0.3 Delta OD/mg/min, p = 0.03 6) was noted in comparison with group II. PaO2 levels tended to be higher i n cGMP-treated animals, but the changes were not significant. Hemodynamic p arameters did not differ between groups. Conclusions. In this large animal model of lung allograft ischemia/reperfus ion injury, 8-Br-cGMP as additive to the flush solution improves posttransp lant lung edema, lipid peroxidation, and neutrophil migration to the allogr aft. This effect is not attributable to improved flush by vasodilation, as we compared 8-Br-cGMP with PGE, given before flush in control animals. (C) 1999 by The Society of Thoracic Surgeons.