title: Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.
abstract: OBJECTIVE
  The rat experimental model of continuous regional arterial infusion of protease inhibitor (CRAI) on acute pancreatitis has yet to be established. Therefore, the aims of this study were (1) to establish the rat experimental model of CRAI and (2) to evaluate the effects of nafamostat on rat severe acute pancreatitis via different routes of administration.
  
  
  METHODS
  The rat internal jugular vein or the celiac artery was infused with nafamostat, and the concentration of nafamostat in the lung and pancreas was measured. After the induction of severe acute pancreatitis, rats received intravenous or regional intraarterial infusion of nafamostat and then concentrations of trypsinogen activated peptide (TAP) and serum interleukin (IL-6), and histologic sections of the pancreas were examined and the 96-hour survival rate was evaluated.
  
  
  RESULTS
  CRAI rats had higher concentrations of nafamostat in the pancreas than those infused intravenously. However, CRAI rats had lower concentrations of nafamostat in the lung that those infused intravenously. CRAI significantly reduced the levels of TAP and pancreatic necrosis. Moreover, the levels of serum IL-6 and the mortality rate were significantly reduced after CRAI compared with the intravenous infusion of nafamostat.
  
  
  CONCLUSIONS
  The effectiveness of the rat experimental model of CRAI on acute pancreatitis was clearly demonstrated. The concentration of nafamostat in the lung and pancreas and the effects of nafamostat differ according to the route of administration.
authors.affiliation: Division of Gastroenterological Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan. y-mikami@surg1.med.tohoku.ac.jp
authors.forename: Yukio
authors.initials: Y
authors.lastname: Mikami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Takeda
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Matsuda
authors.forename: Huang
authors.initials: H
authors.lastname: Qiu-Feng
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Shinichi
authors.initials: S
authors.lastname: Egawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Seiki
authors.initials: S
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D001550:Benzamidines; D002445:Celiac Artery; D004195:Disease Models, Animal; D006146:Guanidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D007261:Infusions, Intra-Arterial / Q000379:methods*; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D007601:Jugular Veins; D008168:Lung; D008297:Male; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D001550:Benzamidines; D006146:Guanidines; D015850:Interleukin-6; D011480:Protease Inhibitors; C032855:nafamostat