TY - JOUR
T1 - Vagal control of mucociliary clearance in murine lungs
T2 - A study in a chronic preparation
AU - Bhashyam, Abhiram R.
AU - Mogayzel, Peter J.
AU - Cleary, Jeffrey C.
AU - Undem, Bradley J.
AU - Kollarik, Marian
AU - Fox, James
AU - Laube, Beth L.
N1 - Funding Information:
The authors wish to thank Kathryn A. Carson, Sc.M. for providing statistical assistance with the analysis of these data. This work was partially funded by the National Institute of Diabetes and Digestive and Kidney Diseases ( R01 DK074480 ) and by the National Cancer Institute ( U24 CA92871 ).
PY - 2010/4/19
Y1 - 2010/4/19
N2 - We conducted several experiments that focused on the effect of vagal control on mucociliary clearance (MCC) in murine lungs. We hypothesized that loss of vagal control by chronic denervation (i.e. vagotomy) would reduce both basal MCC and the increase in MCC typically observed upon stimulation of capsaicin sensitive C-fibers. Vagotomy was performed on the right side of C57BL/6 mice and MCC was measured 5 days later. Mucociliary clearance was measured by gamma scintigraphy after oropharyngeal aspiration of the radioisotope 99mtechnetium and was expressed as the amount of radioactivity removed from the right lung 6 h later. Baseline MCC was unaffected by vagotomy, averaging 6.5 ± 4.9% and 6.8 ± 5.8%, in 6 vagotomized and 6 non-vagotomized mice (controls), respectively. Mucociliary clearance increased significantly to 12.7 ± 5.9% in 9 non-vagotomized mice treated with 1.6 × 10- 9 M capsaicin, a vagally-mediated, nociceptor stimulus (p = 0.041). Capsaicin was admixed with 99mtechnetium and administered by oropharyngeal aspiration. In contrast, MCC was unchanged from control values in 9 vagotomized, capsaicin-treated animals, averaging 6.0 ± 5.5% (p = 0.024). These findings suggest that loss of vagal control through denervation does not affect basal MCC in C57BL/6 mice, but does appear to reduce the capacity of mice to respond to nociceptor agents that stimulate MCC. These data could have implications for patients whose lungs are denervated due to lung transplantation, since they may be at risk for an inadequate MCC response to inhaled irritants and inflammatory mediators, which are also nociceptor stimuli.
AB - We conducted several experiments that focused on the effect of vagal control on mucociliary clearance (MCC) in murine lungs. We hypothesized that loss of vagal control by chronic denervation (i.e. vagotomy) would reduce both basal MCC and the increase in MCC typically observed upon stimulation of capsaicin sensitive C-fibers. Vagotomy was performed on the right side of C57BL/6 mice and MCC was measured 5 days later. Mucociliary clearance was measured by gamma scintigraphy after oropharyngeal aspiration of the radioisotope 99mtechnetium and was expressed as the amount of radioactivity removed from the right lung 6 h later. Baseline MCC was unaffected by vagotomy, averaging 6.5 ± 4.9% and 6.8 ± 5.8%, in 6 vagotomized and 6 non-vagotomized mice (controls), respectively. Mucociliary clearance increased significantly to 12.7 ± 5.9% in 9 non-vagotomized mice treated with 1.6 × 10- 9 M capsaicin, a vagally-mediated, nociceptor stimulus (p = 0.041). Capsaicin was admixed with 99mtechnetium and administered by oropharyngeal aspiration. In contrast, MCC was unchanged from control values in 9 vagotomized, capsaicin-treated animals, averaging 6.0 ± 5.5% (p = 0.024). These findings suggest that loss of vagal control through denervation does not affect basal MCC in C57BL/6 mice, but does appear to reduce the capacity of mice to respond to nociceptor agents that stimulate MCC. These data could have implications for patients whose lungs are denervated due to lung transplantation, since they may be at risk for an inadequate MCC response to inhaled irritants and inflammatory mediators, which are also nociceptor stimuli.
KW - Denervation
KW - Mucociliary clearance
KW - Murine model
KW - Vagal control
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U2 - 10.1016/j.autneu.2009.12.002
DO - 10.1016/j.autneu.2009.12.002
M3 - Article
C2 - 20051324
AN - SCOPUS:77949487564
SN - 1566-0702
VL - 154
SP - 74
EP - 78
JO - Autonomic Neuroscience: Basic and Clinical
JF - Autonomic Neuroscience: Basic and Clinical
IS - 1-2
ER -