title: Oral CPSI-2364 treatment prevents postoperative ileus in swine without impairment of anastomotic healing.
abstract: BACKGROUND
  Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). We demonstrated that orally applicated CPSI-2364 prevents POI in rodents by blockade of p38 MAPK pathway and abrogation of NO production in macrophages. In the present experimental swine study we compared the effect of orally and intravenously administered CPSI-2364 on POI and examined CPSI-2364 effect on anastomotic healing.
  
  
  METHODS
  CPSI-2364 was administered preoperatively via oral or intravenous route. POI was induced by intestinal manipulation of the small bowel. ME specimens were examined by quantitative PCR for CCL2 chemokine gene expression and myeloperoxidase activity. Functional analyzes included measurement of ileal smooth-muscle ex vivo contractility, in vivo intestinal and colonic transit. Furthermore, anastomotic healing of a rectorectostomy after CPSI-2364 treatment was assessed by perianastomotic hydroxyproline concentration, a histochemically evaluated healing score and anastomotic bursting pressure (ABP).
  
  
  RESULTS
  CPSI-2364 abolished inflammation of the ME and improved postoperative smooth muscle contractility and intestinal transit independently of its application route. Hydroxyproline concentration and ABP measurement revealed no wound healing disturbances after oral or intravenous CPSI-2364 treatment whereas histological scoring demonstrated delayed anastomotic healing after intravenous treatment.
  
  
  CONCLUSIONS
  CPSI-2364 effectively prevents POI in swine independently of its application route. Impairment of anastomotic healing could be observed after intravenous but not oral preoperative CPSI-2364 treatment. Subsumed, an oral preoperative administration of CPSI-2364 appears to be a safe and efficient strategy for prophylaxis of POI.
authors.affiliation: Department of Surgery, University of Bonn, Bonn, Germany.
authors.forename: Tim O
authors.initials: TO
authors.lastname: Vilz
authors.forename: Nils
authors.initials: N
authors.lastname: Sommer
authors.forename: Philip
authors.initials: P
authors.lastname: Kahl
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pantelis
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Kalff
authors.forename: Sven
authors.initials: S
authors.lastname: Wehner
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000714:Anastomosis, Surgical; D000818:Animals; D006835:Hydrazones / Q000008:administration & dosage / Q000494:pharmacology*; D006909:Hydroxyproline / Q000378:metabolism; D045823:Ileus / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control*; D012007:Rectum / Q000187:drug effects / Q000601:surgery; D013552:Swine; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000813:Anilides; D006146:Guanidines
chemical_list: D006835:Hydrazones; D006909:Hydroxyproline; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases; C097256:semapimod; D000813:Anilides; D006146:Guanidines