Vagal control of mucociliary clearance in murine lungs: a study in a chronic preparation

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 (99m)technetium and was expressed as the amount of radioactivity removed from the right lung 6h 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 x 10(-9) M capsaicin, a vagally-mediated, nociceptor stimulus (p=0.041). Capsaicin was admixed with (99m)technetium 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.