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Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice.

Jonasson S, Swedin L, Lundqvist M, Hedenstierna G, Dahlén SE, Hjoberg J - Respir. Res. (2008)

Bottom Line: We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. sofia.jonasson@medsci.uu.se

ABSTRACT

Background: Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.

Methods: Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.

Results: DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 +/- 0.3 to 2.8 +/- 0.1 cmH2O.s.mL-1 in healthy mice and 5.1 +/- 0.3 to 3.5 +/- 0.3 cmH2O.s.mL-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 +/- 1.5% to 5.6 +/- 0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 +/- 6.6% to 14.3 +/- 1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).

Conclusion: We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

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Schematic presentation of study design and graph describing tracings and measurements of lung compliance. (A) Experimental protocol. R&Cscan is a program for measuring lung resistance and compliance with the single compartment model. A perturbation of forced oscillation was performed for 4 s (Prime 4, Zrs measurements) and was used in the acute 17-day (OVA'17 and PBS'17 animals) and chronic 98-day protocol (OVA'98 and PBS'98 animals). During A → F, methacholine (MCh) or phosphate buffered saline (PBS) was administrated or nothing was given. MCh or PBS was administrated 20 s after last DI. (B) Tracings of lung compliance (CL) obtained by R&Cscan indicating measurement points for CL (A → F) and ΔCL with and without deep inspirations (DI).
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Figure 1: Schematic presentation of study design and graph describing tracings and measurements of lung compliance. (A) Experimental protocol. R&Cscan is a program for measuring lung resistance and compliance with the single compartment model. A perturbation of forced oscillation was performed for 4 s (Prime 4, Zrs measurements) and was used in the acute 17-day (OVA'17 and PBS'17 animals) and chronic 98-day protocol (OVA'98 and PBS'98 animals). During A → F, methacholine (MCh) or phosphate buffered saline (PBS) was administrated or nothing was given. MCh or PBS was administrated 20 s after last DI. (B) Tracings of lung compliance (CL) obtained by R&Cscan indicating measurement points for CL (A → F) and ΔCL with and without deep inspirations (DI).

Mentions: Common for all mice studied, lung mechanics measurements were assessed every fifth min during a 30 min protocol (Figure 1A). Mice were randomly selected to receive DI, that was given twice during the minute before assessment of lung mechanics, DI is defined as incremental increase and decrease of three times VT during a period of 16 s. Mice not receiving DI, were given normal ventilation for 16 s.


Different effects of deep inspirations on central and peripheral airways in healthy and allergen-challenged mice.

Jonasson S, Swedin L, Lundqvist M, Hedenstierna G, Dahlén SE, Hjoberg J - Respir. Res. (2008)

Schematic presentation of study design and graph describing tracings and measurements of lung compliance. (A) Experimental protocol. R&Cscan is a program for measuring lung resistance and compliance with the single compartment model. A perturbation of forced oscillation was performed for 4 s (Prime 4, Zrs measurements) and was used in the acute 17-day (OVA'17 and PBS'17 animals) and chronic 98-day protocol (OVA'98 and PBS'98 animals). During A → F, methacholine (MCh) or phosphate buffered saline (PBS) was administrated or nothing was given. MCh or PBS was administrated 20 s after last DI. (B) Tracings of lung compliance (CL) obtained by R&Cscan indicating measurement points for CL (A → F) and ΔCL with and without deep inspirations (DI).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291047&req=5

Figure 1: Schematic presentation of study design and graph describing tracings and measurements of lung compliance. (A) Experimental protocol. R&Cscan is a program for measuring lung resistance and compliance with the single compartment model. A perturbation of forced oscillation was performed for 4 s (Prime 4, Zrs measurements) and was used in the acute 17-day (OVA'17 and PBS'17 animals) and chronic 98-day protocol (OVA'98 and PBS'98 animals). During A → F, methacholine (MCh) or phosphate buffered saline (PBS) was administrated or nothing was given. MCh or PBS was administrated 20 s after last DI. (B) Tracings of lung compliance (CL) obtained by R&Cscan indicating measurement points for CL (A → F) and ΔCL with and without deep inspirations (DI).
Mentions: Common for all mice studied, lung mechanics measurements were assessed every fifth min during a 30 min protocol (Figure 1A). Mice were randomly selected to receive DI, that was given twice during the minute before assessment of lung mechanics, DI is defined as incremental increase and decrease of three times VT during a period of 16 s. Mice not receiving DI, were given normal ventilation for 16 s.

Bottom Line: We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. sofia.jonasson@medsci.uu.se

ABSTRACT

Background: Deep inspirations (DI) have bronchodilatory and bronchoprotective effects in healthy human subjects, but these effects appear to be absent in asthmatic lungs. We have characterized the effects of DI on lung mechanics during mechanical ventilation in healthy mice and in a murine model of acute and chronic airway inflammation.

Methods: Balb/c mice were sensitized to ovalbumin (OVA) and exposed to nebulized OVA for 1 week or 12 weeks. Control mice were challenged with PBS. Mice were randomly selected to receive DI, which were given twice during the minute before assessment of lung mechanics.

Results: DI protected against bronchoconstriction of central airways in healthy mice and in mice with acute airway inflammation, but not when OVA-induced chronic inflammation was present. DI reduced lung resistance induced by methacholine from 3.8 +/- 0.3 to 2.8 +/- 0.1 cmH2O.s.mL-1 in healthy mice and 5.1 +/- 0.3 to 3.5 +/- 0.3 cmH2O.s.mL-1 in acute airway inflammation (both P < 0.001). In healthy mice, DI reduced the maximum decrease in lung compliance from 15.9 +/- 1.5% to 5.6 +/- 0.6% (P < 0.0001). This protective effect was even more pronounced in mice with chronic inflammation where DI attenuated maximum decrease in compliance from 44.1 +/- 6.6% to 14.3 +/- 1.3% (P < 0.001). DI largely prevented increased peripheral tissue damping (G) and tissue elastance (H) in both healthy (G and H both P < 0.0001) and chronic allergen-treated animals (G and H both P < 0.0001).

Conclusion: We have tested a mouse model of potential value for defining mechanisms and sites of action of DI in healthy and asthmatic human subjects. Our current results point to potent protective effects of DI on peripheral parts of chronically inflamed murine lungs and that the presence of DI may blunt airway hyperreactivity.

Show MeSH
Related in: MedlinePlus