Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia

Study objectives: Inhalation of nitric oxide (NO) can ameliorate pulmonary ischemia/reperfusion (I/R) injury of the lung in several experimental models, but toxic effects of NO were also reported. Here we investigate whether NO inhalation for a short period prior to surgery is sufficient to prevent symptoms of lung I/R injury, especially the inflammatory response. Design: Using an in situ porcine lung model, normothermic left lung ischemia was maintained for 90 min, followed by a 5-h reperfusion period (group 1, n = 7). In group 2 (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group 3 (n = 7) underwent sham surgery without NO inhalation or ischemia. Measurements: Oxygenation and hemodynamic parameters were measured as indicators of lung functional impairment. Plasma levels of interleukin (IL)-1beta, IL-6, and transforming growth factor (TGF)-beta1 were determined throughout the I/R maneuver. In addition, tissue macrophages were analyzed by lectin binding. Results: Symptoms of I/R injury (pulmonary hypertension and decreased oxygenation) in group I animals were attenuated by NO inhalation. The reperfusion-induced increases of the levels of IL-1beta and IL-6 in plasma were reduced by NO pretreatment. A peak of TGF-beta1 immediately after NO administration was observed in group 2, but not in groups 1 and 3. There was no significant effect of NO on tissue macrophages. Conclusion: NO inhalation for a short period prior to lung I/R is sufficient to protect against pulmonary hypertension, impaired oxygenation, and the inflammatory response of pulmonary I/R injury.