title: Stimulation of Central α2 Receptors Attenuates Experimental Necrotizing Pancreatitis.
abstract: OBJECTIVE
  Severe necrotizing pancreatitis (SNP) is a disease with relevant morbidity and mortality until today. No specific therapy is in sight. Central α2 agonists such as clonidine and dexmedetomidine are known to have anti-inflammatory effects though the cholinergic anti-inflammatory pathway and are implemented in the clinical routine as adjunct sedative drugs. Their potential effect on SNP has not yet been tested.
  
  
  METHODS
  Severe necrotizing pancreatitis was induced in male Wistar rats. Four treatment groups received either clonidine or dexmedetomidine before (prophylactic) or after induction of SNP (therapeutic). After 12 hours, pancreatic morphologic injury, systemic proinflammatory high-mobility group box 1 protein, and pancreatic and pulmonary myeloperoxidase levels were evaluated.
  
  
  RESULTS
  Severe necrotizing pancreatitis was fully established 12 hours after induction. "Prophylactic" and "therapeutic" administration of clonidine and dexmedetomidine reduced pancreatic morphologic injury (P < 0.05 vs SNP), serum proinflammatory high-mobility group box 1 protein (P < 0.0001 vs SNP), as well as pancreatic and pulmonary myeloperoxidase levels (P < 0.01 vs SNP).
  
  
  CONCLUSIONS
  Prophylactic and therapeutic applications of the central α2 agonists clonidine and dexmedetomidine are effective to attenuate local and systemic injury in experimental SNP and should be evaluated in the clinical setting.
authors.affiliation: From the Departments for *General, Visceral, and Transplantation Surgery and †Anaesthesiology, University of Heidelberg, Heidelberg; and ‡Department for General, Visceral, Transplantation, Thoracic, and Vascular Surgery, University of Munich, Munich, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schneider
authors.forename: Bahar
authors.initials: B
authors.lastname: Jabrailova
authors.forename: Mohammed
authors.initials: M
authors.lastname: Salem
authors.forename: Karl
authors.initials: K
authors.lastname: Kilk
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brenner
authors.forename: Oliver
authors.initials: O
authors.lastname: Strobel
authors.forename: Thilo
authors.initials: T
authors.lastname: Hackert
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D020927:Dexmedetomidine / Q000494:pharmacology; D006002:Glycodeoxycholic Acid; D024243:HMGB1 Protein / Q000097:blood; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018836:Inflammation Mediators; D018341:Receptors, Adrenergic, alpha-2; D006002:Glycodeoxycholic Acid; D020927:Dexmedetomidine; D009195:Peroxidase; D003000:Clonidine