Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury
2008 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no 5, R131- p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
BioMed Central , 2008. Vol. 12, no 5, R131- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-107008DOI: 10.1186/cc7099ISI: 000261561100019PubMedID: 18954441OAI: oai:DiVA.org:uu-107008DiVA: diva2:227556