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Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice.

Jahn N, Lamberts RR, Busch CJ, Voelker MT, Busch T, Koel-Simmelink MJ, Teunissen CE, Oswald DD, Loer SA, Kaisers UX, Weimann J - Respir. Res. (2015)

Bottom Line: 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.Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany. nora.jahn@medizin.uni-leipzig.de.

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 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.

No MeSH data available.


Related in: MedlinePlus

Double occlusion; Original recording of two successive double occlusion maneuvers (↓) during normoxic (21 % O2) and hypoxic (1 % O2) ventilation in an isolated perfused mouse lung. PAP = pulmonary artery pressure, LAP = left atrial pressure, PCP = pulmonary capillary pressure. Note that hypoxic ventilation predominantly causes arterial rather than venous vasoconstriction. *denotes interruption of ventilation
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Fig2: Double occlusion; Original recording of two successive double occlusion maneuvers (↓) during normoxic (21 % O2) and hypoxic (1 % O2) ventilation in an isolated perfused mouse lung. PAP = pulmonary artery pressure, LAP = left atrial pressure, PCP = pulmonary capillary pressure. Note that hypoxic ventilation predominantly causes arterial rather than venous vasoconstriction. *denotes interruption of ventilation

Mentions: Pulmonary capillary pressure was estimated by the double occlusion technique (DBO) to evaluate the resistance in the pulmonary circulation [33, 34]. This technique is done as follows: after turning off the respirator in expiration, inflow and outflow through the lungs were stopped simultaneously for 5 s using two electromagnetic micro-valves (Clippard Minimatic, Cincinnati, OH). PAP and LAP were allowed to equilibrate and the resulting pressure represents the pressure in the pulmonary capillaries (PCP) [33] (see Fig. 2). During constant flow perfusion, total pulmonary vascular resistance is represented by the pressure drop across the pulmonary vasculature, expressed as the difference between PAP and LAP. Thus, the contribution of the pre-capillary, arterial part of pulmonary vasculature to total pulmonary vascular resistance can be expressed as PAP reduced by PCP and accordingly, the contribution of the post-capillary, venous part as PCP minus LAP. DBO values were included when a stable PCP curve was registered with complete equilibration of PAP and LAP (80 % inclusion).Fig. 2


Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice.

Jahn N, Lamberts RR, Busch CJ, Voelker MT, Busch T, Koel-Simmelink MJ, Teunissen CE, Oswald DD, Loer SA, Kaisers UX, Weimann J - Respir. Res. (2015)

Double occlusion; Original recording of two successive double occlusion maneuvers (↓) during normoxic (21 % O2) and hypoxic (1 % O2) ventilation in an isolated perfused mouse lung. PAP = pulmonary artery pressure, LAP = left atrial pressure, PCP = pulmonary capillary pressure. Note that hypoxic ventilation predominantly causes arterial rather than venous vasoconstriction. *denotes interruption of ventilation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4587582&req=5

Fig2: Double occlusion; Original recording of two successive double occlusion maneuvers (↓) during normoxic (21 % O2) and hypoxic (1 % O2) ventilation in an isolated perfused mouse lung. PAP = pulmonary artery pressure, LAP = left atrial pressure, PCP = pulmonary capillary pressure. Note that hypoxic ventilation predominantly causes arterial rather than venous vasoconstriction. *denotes interruption of ventilation
Mentions: Pulmonary capillary pressure was estimated by the double occlusion technique (DBO) to evaluate the resistance in the pulmonary circulation [33, 34]. This technique is done as follows: after turning off the respirator in expiration, inflow and outflow through the lungs were stopped simultaneously for 5 s using two electromagnetic micro-valves (Clippard Minimatic, Cincinnati, OH). PAP and LAP were allowed to equilibrate and the resulting pressure represents the pressure in the pulmonary capillaries (PCP) [33] (see Fig. 2). During constant flow perfusion, total pulmonary vascular resistance is represented by the pressure drop across the pulmonary vasculature, expressed as the difference between PAP and LAP. Thus, the contribution of the pre-capillary, arterial part of pulmonary vasculature to total pulmonary vascular resistance can be expressed as PAP reduced by PCP and accordingly, the contribution of the post-capillary, venous part as PCP minus LAP. DBO values were included when a stable PCP curve was registered with complete equilibration of PAP and LAP (80 % inclusion).Fig. 2

Bottom Line: 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.Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Leipzig, Leipzig, Germany. nora.jahn@medizin.uni-leipzig.de.

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 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.

No MeSH data available.


Related in: MedlinePlus