eprintid: 19551 rev_number: 14 eprint_status: archive userid: 1589 dir: disk0/00/01/95/51 datestamp: 2016-01-19 10:25:51 lastmod: 2024-05-17 19:58:01 status_changed: 2016-01-19 10:25:51 type: article metadata_visibility: show creators_name: Jahn, Nora creators_name: Lamberts, Regis R. creators_name: Busch, Cornelius J. creators_name: Voelker, Maria T. creators_name: Busch, Thilo creators_name: Koel-Simmelink, Marleen J. A. creators_name: Teunissen, Charlotte E creators_name: Oswald, Daniel D. creators_name: Loer, Stephan A. creators_name: Kaisers, Udo X. creators_name: Weimann, Jörg title: Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice subjects: ddc-610 divisions: i-910300 abstract: 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 (FiO2 = 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 3rd and 6th 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. date: 2015 publisher: BioMed Central id_scheme: DOI ppn_swb: 1656066815 own_urn: urn:nbn:de:bsz:16-heidok-195512 language: eng bibsort: JAHNNORAINHALEDCAR2015 full_text_status: public publication: Respiratory research volume: 16 number: 119 place_of_pub: London pagerange: 1-12 issn: 1465-993X citation: Jahn, Nora ; Lamberts, Regis R. ; Busch, Cornelius J. ; Voelker, Maria T. ; Busch, Thilo ; Koel-Simmelink, Marleen J. A. ; Teunissen, Charlotte E ; Oswald, Daniel D. ; Loer, Stephan A. ; Kaisers, Udo X. ; Weimann, Jörg (2015) Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice. Respiratory research, 16 (119). pp. 1-12. ISSN 1465-993X document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19551/1/12931_2015_Article_274.pdf