title: Laparoscopic surgery and the parasympathetic nervous system.
abstract: BACKGROUND
  Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway.
  
  
  METHODS
  In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Serum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments.
  
  
  CONCLUSIONS
  CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 665, Baltimore, MD, 21287-4665, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Fuentes
authors.forename: E J
authors.initials: EJ
authors.lastname: Hanly
authors.forename: A R
authors.initials: AR
authors.lastname: Aurora
authors.forename: A
authors.initials: A
authors.lastname: De Maio
authors.forename: S P
authors.initials: SP
authors.lastname: Shih
authors.forename: M R
authors.initials: MR
authors.lastname: Marohn
authors.forename: M A
authors.initials: MA
authors.lastname: Talamini
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002245:Carbon Dioxide; D002799:Cholinergic Fibers; D007107:Immune System / Q000503:physiopathology*; D010535:Laparoscopy; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009407:Nerve Block; D009434:Neural Pathways / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D010276:Parasympatholytics / Q000494:pharmacology; D010812:Physical Stimulation; D011028:Pneumoperitoneum, Artificial; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D008070:Lipopolysaccharides; D010276:Parasympatholytics; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D001285:Atropine