title: Regional sympathetic blockade attenuates activation of intestinal macrophages and reduces gut barrier failure.
abstract: BACKGROUND
  Endotoxin-induced activation of monocytes may lead to extravasation of cells, excessive production of nitric oxide, and subsequent epithelial injury in the gut. Regional sympathetic blockade by means of thoracic epidural anesthesia has been implicated to protect the epithelial barrier. This study tested the hypothesis that thoracic epidural anesthesia decreases epithelial permeability by attenuating monocytic production of nitric oxide and nitrosative stress.
  
  
  METHODS
  Rats were anesthetized, hemodynamically monitored, and mechanically ventilated. Endotoxemia was induced by an intravenous bolus injection of Escherichia coli lipopolysaccharide. Either lidocaine 2% or normal saline was injected as a bolus, followed by a continuous infusion via an epidural catheter. Three hundred minutes after injection of lipopolysaccharide or normal saline, gut epithelial permeability to fluorescein isothiocyanate-dextran (4 kDa), intestinal expression of inducible nitric oxide synthase by macrophages, and lipid peroxidation represented by 8-isoprostane tissue concentration were quantified.
  
  
  RESULTS
  Thoracic epidural anesthesia significantly attenuated the endotoxin-induced increases in gut epithelial permeability (437 [293, 492] vs. 628 [532, 1,042] ng/ml, median [quartiles], P = 0.03), expression of nitric oxide synthase (2 [1,2] vs. 7 [5,8] cells per 384 µm(2), P = 0.003), macrophage infiltration, and lipid peroxidation (22,460 ± 11,476 vs. 37,840 ± 17,551 pg/ml, mean ± SD, P = 0.05).
  
  
  CONCLUSIONS
  Thoracic epidural anesthesia attenuates endotoxin-induced gut epithelial injury. This is likely due to a decrease in monocytic extravasation and intestinal nitrosative stress. As possible mechanisms, direct nerve-immune interplay, a reduction in plasma catecholamines, or a systemic lidocaine effect has to be considered.
authors.affiliation: Department of Anesthesiology, Emergency Medicine and Critical Care Medicine, Universitätsmedizin Göttingen, Göttingen, Germany. joern.schaeper@med.uni-goettingen.de
authors.forename: Jörn
authors.initials: J
authors.lastname: Schäper
authors.forename: Antje
authors.initials: A
authors.lastname: Wagner
authors.forename: Fabian
authors.initials: F
authors.lastname: Enigk
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brell
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Helmut
authors.initials: H
authors.lastname: Habazettl
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
mesh_terms: D000767:Anesthesia, Epidural / Q000379:methods; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001340:Autonomic Nerve Block / Q000379:methods*; D019446:Endotoxemia; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D028421:Isoprostanes / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000779:Anesthetics, Local; D028421:Isoprostanes; D009569:Nitric Oxide; D008012:Lidocaine; D052247:Nitric Oxide Synthase Type II