TY - JOUR
T1 - Long-term effects of nafamostat and imipenem on experimental acute pancreatitis in rats
AU - Naruse, Satoru
AU - Wang, Youxue
AU - Kitagawa, Motoji
AU - Ishiguro, Hiroshi
AU - Seki, Yasunaga
AU - Ozaki, Tsuyoshi
AU - Hayakawa, Tetsuo
PY - 2000
Y1 - 2000
N2 - Long-term effects of nafamostat mesylate, a protease inhibitor, and imipenem, an antibiotic, on trypsin-taurocholate-induced acute pancreatitis were studied in rats. Sham-operated rats infused with a buffer solution into the pancreatic duct served as controls. Nafamostat (1 mg/kg), imi-· penem (10 mg/kg), or imipenem + nafamostat in saline was injected subcutaneously 0.25, 3, 24, and 48 hours after the induction of pancreatitis. In untreated rats and control rats, saline was injected at the same intervals as in the treated rats. All rats in an untreated group died within 3.5 days (median survival, 1.25 day) after the induction of pancreatitis. The 2-week survival rate was significantly (p < 0.05) improved by a combination of nafamostat and imipenem (42%), but not by nafamostat (17%), or imipenem (8%) alone. Bacterial culture at 24 hours revealed infection of necrotic pancreatic tissues and ascites by intestinal bacteria in all untreated rats but not in control rats. Bacterial counts were significantly reduced by imipenem, but not by nafamostat. In conclusion, bacterial infection occurred within 24 hours after the induction of trypsin-taurocholate pancreatitis in rats. Early treatment with nafamostat + imipenem, but not nafamostat or imipenem alone, improves long-term survival.
AB - Long-term effects of nafamostat mesylate, a protease inhibitor, and imipenem, an antibiotic, on trypsin-taurocholate-induced acute pancreatitis were studied in rats. Sham-operated rats infused with a buffer solution into the pancreatic duct served as controls. Nafamostat (1 mg/kg), imi-· penem (10 mg/kg), or imipenem + nafamostat in saline was injected subcutaneously 0.25, 3, 24, and 48 hours after the induction of pancreatitis. In untreated rats and control rats, saline was injected at the same intervals as in the treated rats. All rats in an untreated group died within 3.5 days (median survival, 1.25 day) after the induction of pancreatitis. The 2-week survival rate was significantly (p < 0.05) improved by a combination of nafamostat and imipenem (42%), but not by nafamostat (17%), or imipenem (8%) alone. Bacterial culture at 24 hours revealed infection of necrotic pancreatic tissues and ascites by intestinal bacteria in all untreated rats but not in control rats. Bacterial counts were significantly reduced by imipenem, but not by nafamostat. In conclusion, bacterial infection occurred within 24 hours after the induction of trypsin-taurocholate pancreatitis in rats. Early treatment with nafamostat + imipenem, but not nafamostat or imipenem alone, improves long-term survival.
KW - Acute necrotizing pancreatitis
KW - Antibiotics
KW - Bacterial infection
KW - Protease inhibitor
KW - Survival
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U2 - 10.1097/00006676-200010000-00011
DO - 10.1097/00006676-200010000-00011
M3 - Article
C2 - 11039474
AN - SCOPUS:0033807063
SN - 0885-3177
VL - 21
SP - 290
EP - 295
JO - Pancreas
JF - Pancreas
IS - 3
ER -