The role of the vagus nerve on dexmedetomidine promoting survival and lung protection in a sepsis model in rats

Background: Sepsis often results in acute lung injury (ALI). Dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in lipopolysaccharide (LPS)-induced ALI rats. Methods: The bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed as sham surgery. After LPS administration, Dex antagonist yohimbine (YOH) and/or Dex was injected intraperitoneally to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores. The plasma concentrations of interleukin 1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), catecholamine and acetylcholine were measured with enzyme-linked immunosorbent assay. Results: The median survival time of LPS-induced ALI rats was prolonged by Dex (22 h, 95% CI, [24.46, 92.20]) vs. 14 h, 95% CI, [14.60, 89.57] of the LPS control group, P < 0.05), and the ALI score was reduced by Dex (6.5, 95% CI, [5.23, 8.10] vs. 11.5, 95% CI, [10.23, 13.10] in the LPS group, P < 0.01). However, these protective effects were significantly decreased by either YOH administration or vagotomy. Dex decreased LPS-induced IL1 beta, TNF-alpha, and catecholamine but increased acetylcholine in blood serum; these effects of Dex was partially abolished by vagotomy. Conclusions: Our data suggested that Dex increased vagal nerve tone that partially contributed to its antiinflammatory and lung-protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and alpha 2-adrenoceptor activation, respectively.

Automated summary

This study found that Dexmedetomidine plays a role in protecting the lungs by increasing vagal nerve tone. The indirect anti-inflammatory effects and direct cytoprotective effects of Dexmedetomidine are likely achieved through increased vagal nerve tone and activation of alpha 2-adrenoceptors, respectively.