title: Effects of vagus nerve stimulation and vagotomy on systemic and pulmonary inflammation in a two-hit model in rats.
abstract: Pulmonary inflammation contributes to ventilator-induced lung injury. Sepsis-induced pulmonary inflammation (first hit) may be potentiated by mechanical ventilation (MV, second hit). Electrical stimulation of the vagus nerve has been shown to attenuate inflammation in various animal models through the cholinergic anti-inflammatory pathway. We determined the effects of vagotomy (VGX) and vagus nerve stimulation (VNS) on systemic and pulmonary inflammation in a two-hit model. Male Sprague-Dawley rats were i.v. administered lipopolysaccharide (LPS) and subsequently underwent VGX, VNS or a sham operation. 1 hour following LPS, MV with low (8 mL/kg) or moderate (15 mL/kg) tidal volumes was initiated, or animals were left breathing spontaneously (SP). After 4 hours of MV or SP, rats were sacrificed. Cytokine and blood gas analysis was performed. MV with 15, but not 8 mL/kg, potentiated the LPS-induced pulmonary pro-inflammatory cytokine response (TNF-α, IL-6, KC: p<0.05 compared to LPS-SP), but did not affect systemic inflammation or impair oxygenation. VGX enhanced the LPS-induced pulmonary, but not systemic pro-inflammatory cytokine response in spontaneously breathing, but not in MV animals (TNF-α, IL-6, KC: p<0.05 compared to SHAM), and resulted in decreased pO(2) (p<0.05 compared to sham-operated animals). VNS did not affect any of the studied parameters in both SP and MV animals. In conclusion, MV with moderate tidal volumes potentiates the pulmonary inflammatory response elicited by systemic LPS administration. No beneficial effects of vagus nerve stimulation performed following LPS administration were found. These results questions the clinical applicability of stimulation of the cholinergic anti-inflammatory pathway in systemically inflamed patients admitted to the ICU where MV is initiated.
authors.affiliation: Department of Intensive Care Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.kox@ic.umcn.nl
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.forename: Michiel
authors.initials: M
authors.lastname: Vaneker
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: Cornelia W
authors.initials: CW
authors.lastname: Hoedemaekers
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014628:Vagotomy; D014630:Vagus Nerve / Q000276:immunology / Q000503:physiopathology; D055536:Vagus Nerve Stimulation; D055397:Ventilator-Induced Lung Injury / Q000276:immunology* / Q000503:physiopathology
chemical_list: D054360:Chemokine CXCL1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha