The effect of gabexate mesilate on pancreatic and hepatic microcirculation in acute experimental pancreatitis in rats.
Microcirculatory derangements are important early features in many organs during the process of acute pancreatitis. However, dynamic evaluation of these factors has been difficult. Antiprotease has long been used for the treatment of acute pancreatitis, although its effects and mechanism have not been fully elucidated. The involvement of proteases and microcirculatory derangement early in the course of acute pancreatitis are the main concern of this study. A severe acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by adding caerulein (15 microg/kg/ hr) in intravenous infusion fluid and intraductal injection of 0.1 ml glycodeoxycholic acid (5 mM). Gabexate mesilate [GM; ethyl-4-(6-guanidinohexanoyloxy)benzoate methanesulfonate], a synthetic antiprotease, was infused intravenously in doses of 0.01, 0.1, 1, and 10 mg as a therapeutic intervention in this model. Pathology hematocrit, serum amylase level, and glutamic-oxaloacetic transaminase (GOT) levels were used to confirm the severity of disease and effect of therapy. In vivo microscopic technique was used as a investigating tool in this study of microcirculatory derangement in pancreas and liver, 8 hr after induction of acute pancreatitis. GM can significantly improve pathologic criteria and changes of serum amylase levels in the range of 1-10 mg/kg/hr. The severity of changes of hematocrit and GOT was significantly lessened with GM in the range of 0.1-10 mg/kg/hr. This agent also could improve the microcirculatory environment in pancreas and liver after induction of acute pancreatitis according to the parameters, such as flow velocity and rolling leukocyte phenomenon, in the range of 1-10 mg/kg/hr. According to our observation, severity of hyperpermeability had not changed with the treatment of GM. These results indicated the beneficial effects of GM on pancreatic and hepatic microcirculation early in the course of acute pancreatitis. The beneficial effects were noted in serum parameters and hematocrit. The importance of protease activation and remote organ dysfunction is emphasized in the course of acute pancreatitis from this study.
Chen
H M
HM
Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan.
Hwang
T L
TL
Chen
M F
MF
D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000502:physiology; D016670:Gabexate / Q000494:pharmacology*; D007962:Leukocytes / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010179:Pancreas / Q000098:blood supply*; D010195:Pancreatitis / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology
D016670:Gabexate; D002108:Ceruletide