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

• Published in: Critical care (London, England) England), 2008-01, Vol.12 (5), p.R131-R131, Article R131
• Main Authors: Trachsel, Sebastien, Deby-Dupont, Ginette, Maurenbrecher, Edwige, Nys, Monique, Lamy, Maurice, Hedenstierna, Göran
• Format: Article
• Language: English
• Subjects: Acute respiratory distress syndrome; Administration, Inhalation; Animal models in research; Animals; Care and treatment; Disease Models, Animal; Endotoxins - toxicity; Female; Health aspects; Inflammation Mediators - blood; Lung Injury - blood; Lung Injury - chemically induced; Lung Injury - drug therapy; Male; MEDICIN; MEDICINE; Nitric oxide; Nitric Oxide - administration & dosage; Nitric Oxide - adverse effects; Physiological aspects; Pulmonary gas exchange; Sus scrofa
• ISSN: 1364-8535; 1466-609X; 1466-609X; 1364-8535
• DOI: 10.1186/cc7099

Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. 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 > or = 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.