title: Isoflurane post-conditioning protects against intestinal ischemia-reperfusion injury and multiorgan dysfunction via transforming growth factor-β1 generation.
abstract: OBJECTIVE
  This study examined volatile anesthetic-mediated protection against intestinal ischemia-reperfusion injury (IRI).
  
  
  BACKGROUND
  Intestinal IRI is a devastating complication in the perioperative period leading to systemic inflammation and multiorgan dysfunction. Volatile anesthetics, including isoflurane, have anti-inflammatory effects. We aimed to determine whether isoflurane, given after intestinal ischemia, protects against intestinal IRI and the mechanisms involved in this protection.
  
  
  METHODS
  : After IACUC approval, mice were anesthetized with pentobarbital and subjected to 30 minutes of superior mesenteric artery ischemia, followed by 4 hours of equianesthetic doses of pentobarbital or isoflurane. Five hours after reperfusion, small intestine tissues were analyzed for morphological injury, apoptosis, neutrophil infiltration, proinflammatory mRNAs, and TGF-(Transforming Growth Factor-)β1 levels. We also assessed hepatic and renal injury after intestinal IRI.
  
  
  RESULTS
  Intestinal IRI with pentobarbital led to significant small intestinal dysfunction with increased mucosal injury, TUNEL (transferase biotin-dUTP nick end-labeling)-positive cells, neutrophil infiltration, and proinflammatory mRNAs as well as elevated plasma alanine aminotransferase and creatinine levels. Isoflurane exposure after IRI led to significant attenuation of intestinal, hepatic, and renal injuries. Furthermore, the protective effects of isoflurane were abolished by treatment with a TGF-β1 neutralizing antibody before induction of IRI. Finally, isoflurane exposure led to increased TGF-β1 levels in intestinal epithelial cells and in plasma.
  
  
  CONCLUSIONS
  Our findings demonstrate that isoflurane post-conditioning protects against small intestinal injury and hepatic and renal dysfunction after severe intestinal IRI via induction of intestinal epithelial TGF-β1. Our findings support therapeutic applications of volatile anesthetics during the intraoperative and postoperative periods and imply an important role of TGF-β1 signaling in modulating multiorgan injury.
authors.affiliation: Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
authors.forename: Minjae
authors.initials: M
authors.lastname: Kim
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Park
authors.forename: Mihwa
authors.initials: M
authors.lastname: Kim
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Lee
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D007422:Intestines / Q000098:blood supply*; D057775:Ischemic Postconditioning; D007530:Isoflurane / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*
chemical_list: D018685:Anesthetics, Inhalation; D053773:Transforming Growth Factor beta1; D007530:Isoflurane