Inhaled carbon monoxide protects timedependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice

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Abstract

© 2015 Jahn et al. Background: Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it's biochemical mechanisms and effects on inflammatory reactions. Methods: Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO 2 = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured. Results: HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3 rd and 6 th hour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines. Conclusion: Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

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Jahn, N., Lamberts, R. R., Busch, C. J., Voelker, M. T., Busch, T., Koel-Simmelink, M. J. A., … Weimann, J. (2015). Inhaled carbon monoxide protects timedependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice. Respiratory Research, 16(1). https://doi.org/10.1186/s12931-015-0274-7

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