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Open Access Research

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

Sebastien Trachsel12, Ginette Deby-Dupont34, Edwige Maurenbrecher1, Monique Nys34, Maurice Lamy34 and Göran Hedenstierna1*

Author Affiliations

1 Department of Medical Sciences, Clinical Physiology, Uppsala University, S-75185 Uppsala, Sweden

2 Department of Anesthesiology, University Hospital, Inselspital Bern, CH-3010 Bern, Switzerland

3 Department of Anaesthesia and Intensive Care Medicine, University Hospital of Liège, Domaine du Sart Tilman – B35, B-4000, Liège, Belgium

4 Centre for Oxygen Research and Development, Institute of Chemistry, B6a, University of Liège, Sart Tilman, Belgium University of Liège, B-4000 Liege, Belgium

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Critical Care 2008, 12:R131  doi:10.1186/cc7099

Published: 27 October 2008



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 ≥ 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.