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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

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

ET-1 may therefore be involved in mediating the response to INO.