Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion.Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 ≥ 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO.ET-1 may therefore be involved in mediating the response to INO.Despite years of research and efforts for specific treatments of acute respiratory distress syndrome (ARDS), mortality remains significant [1]. A symptomatic approach aimed at fluid restriction, diuresis, reducing pulmonary hypertension and improving arterial oxygenation are the goals of therapy. The use of intravenous vasodilators to reduce pulmonary hypertension is limited because of deleterious side effects. Arterial oxygenation may worsen because of increased blood flow to nonventilated areas of the lung and systemic effects that can result in hypotension [2]. Inhaled nitric oxide (INO) allows selective pulmonary vasodilation and improves arterial oxygenation by redistribution of blood flow towards better ventilated parenchyma [3]. The clinical application of INO in ARDS and septic