Rat experimental model of continuous regional arterial infusion of protease inhibitor and its effects on severe acute pancreatitis.
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.
Mikami
Yukio
Y
Division of Gastroenterological Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan. y-mikami@surg1.med.tohoku.ac.jp
Takeda
Kazunori
K
Matsuda
Kazuhisa
K
Qiu-Feng
Huang
H
Fukuyama
Shoji
S
Egawa
Shinichi
S
Sunamura
Makoto
M
Matsuno
Seiki
S
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
D001550:Benzamidines; D006146:Guanidines; D015850:Interleukin-6; D011480:Protease Inhibitors; C032855:nafamostat