Protection against lung graft injury from brain-dead donors with carbon monoxide, biliverdin, or both

BACKGROUND: The process of brain death can induce acute lung injury in donors and aggravate ischemia-reperfusion injury in grafts. Carbon monoxide (CO) and biliverdin (BV) have been shown to attenuate ischemia-reperfusion injury. We therefore examined if the administration of both CO and BV provide enhanced cytoprotection against lung graft injury from brain-dead (BD) rat donors. METHODS: Brain death was induced in all donors, after which they were observed for 1.5 hours and then underwent lung transplantation. The recipients were ventilated with 40% oxygen (control group), ventilated with 250 ppm CO in 40% oxygen (CO group), treated with BV (35 mg/kg) intraperitoneally (BV group), or treated with CO and BV conjointly (COBV group) before transplantation (n = 8 each group). The recipients were sacrificed 2 hours after lung transplantation by exsanguination. Serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assay. RESULTS: CO and/or BV treatment attenuated partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (Fio(2)) aggravation in the recipients after reperfusion, reduced the wet weight/dry weight ratio, decreased the lung injury score, inhibited the activity of myeloperoxidase in grafts, and decreased serum levels of IL-8 and TNF-alpha compared with the control group (p < 0.05). The COBV group had significantly decreased malonaldehyde levels and increased superoxide dismutase levels in lung grafts compared with the CO group (p <0.05). The static pressure-volume curve of the lungs was ameliorated in the CO group, BV group, and COBV group compared with the control group (p <0.05). CONCLUSIONS: CO and BV exert protective effects through anti-inflammatory and anti-oxidant mechanisms, and dual treatment provided enhanced cytoprotection against lung graft injury from BD rat donors. J Heart Lung Transplant 2011;30:460-6 (C) 2011 International Society for Heart and Lung Transplantation. All rights reserved.