Effects of Vagus Nerve Stimulation and Vagotomy on Systemic and Pulmonary Inflammation in a Two-Hit Model in Rats
Open Access
- 6 April 2012
- journal article
- biology
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (4), e34431
- https://doi.org/10.1371/journal.pone.0034431
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: p2 (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.Keywords
This publication has 38 references indexed in Scilit:
- Activation of Nicotinic Cholinergic Receptors Prevents Ventilator-Induced Lung Injury in RatsPLOS ONE, 2011
- Ventilator-induced lung injury: The anatomical and physiological frameworkCritical Care Medicine, 2010
- Ventilator-Induced Inflammatory Response in Lipopolysaccharide-Exposed Rat Lung Is Mediated by Angiotensin-Converting EnzymeThe American Journal of Pathology, 2010
- Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy miceCritical Care, 2009
- Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemiaProceedings of the National Academy of Sciences, 2008
- Pharmacologic cholinesterase inhibition improves survival in experimental sepsis*Critical Care Medicine, 2008
- High molecular weight hyaluronan: a possible new treatment for sepsis-induced lung injury - a preclinical study in mechanically ventilated ratsCritical Care, 2008
- Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat modelThorax, 2007
- Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsisThe Journal of Experimental Medicine, 2006
- Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammationNature, 2002