INHALED NITRIC-OXIDE ATTENUATES REPERFUSION INJURY IN NON-HEARTBEATING-DONOR LUNG TRANSPLANTATION

Background. Non-heartbeating-donor (NHBD) lung transplantation could h elp reduce the current organ shortage. Polymorphonuclear neutrophil (P MN) activation plays a pivotal role in ischemia-reperfusion injury (I- R), and can be inhibited by nitric oxide (NO). We hypothesized that in haled NO might be beneficial in NHBD lung transplantation. Methods. Th e effect of inhaled NO on PMNs was studied by measuring in vivo PMN lu ng sequestration (myeloperoxidase activity) and adhesion of recipient circulating PMNs to cultured pulmonary artery endothelial cells (PAECs ) in vitro. Pigs were randomly assigned to an NO or a control group (n =9 each). In the NO group, cadavers and recipients were ventilated wit h oxygen and 30 parts per million of NO. After 3 hr of postmortem in s itu warm ischemia and 2 hr of cold ischemia, left allotransplantation was performed. The right pulmonary artery was ligated, and hemodynamic and gas exchange data were recorded hourly for 9 hr. Recipient PMN ad herence to tumor necrosis factor-alpha- and calcium ionophore-stimulat ed PAECs was measured before and after reperfusion, and lung PMN seque stration was determined after death. Results. NO-treated animals exhib ited lowered pulmonary vascular resistance (P<0.01), as well as improv ed oxygenation (P<0.01) and survival (P<0.05). Adhesion of PMNs to PAE Cs was inhibited in the NO group before (P<0.001) and after reperfusio n (P<0.0001). Lung PMN sequestration was reduced by NO (P<0.05). Concl usions. Inhaled NO attenuates I-R injury after NHBD lung transplantati on. This is likely due to the prevention of I-R-induced pulmonary vaso constriction and to the direct effect on peripheral blood PMN adhesion to endothelium, which results in reduced sequestration and tissue inj ury.