title: Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.
abstract: BACKGROUND
  During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function.
  
  
  METHODS
  We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion.
  
  
  CONCLUSIONS
  Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Schulte
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Giessen, Germany. Electronic address: christoph.lichtenstern@chiru.med.uni-giessen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichtenstern
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Henrich
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Giessen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
mesh_terms: D000758:Anesthesia; D000818:Animals; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D019446:Endotoxemia / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew; D012772:Shock, Septic / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014628:Vagotomy; D014630:Vagus Nerve / Q000473:pathology*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D002795:Choline O-Acetyltransferase; D002332:Carnitine O-Acetyltransferase
keywords: Acetylcholine; Cholinergic anti-inflammatory reflex; Endotoxemia; Septic cardiomyopathy; Vagus nerve stimulation