Gabexate mesilate improves pancreatic microcirculation and reduces lung edema in a rat model of acute pancreatitis

Han Ming Chen*, Ming Hwang Shyr, Miin Fu Chen

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

We evaluated the effects of a protease inhibitor on the progression of acute pancreatitis in rats. The model was selected and modified to mimic an intermediate stage of the disease. The degree of microcirculatory) derangement in the pancreas and of lung edema was determined to assess the effects of gabexate mesilate (ethyl-4-{6-guanidinohexanoyloxy} benzoate methane sulfonate), a synthetic antiprotease, in acute pancreatitis. Male Sprague-Dawley rats (225-275 g) were used. Experimental pancreatitis was established by four intramuscular injections of cerulein (50 μg/kg) at 1 hour intervals. Lipopolysaccharide (10 mg/kg) was injected intraperitoneally as an acute septic challenge. Gabexate mesilate was infused intravenously 6 hours after the initiation of induction of acute pancreatitis at doses of 0.01, 0.1, 1, or 10 mg/kg/h. Microcirculatory changes in the pancreas were studied using in vivo microscopy. All animals survived until the end of the experiments. Gabexate mesilate significantly improved pathologic criteria and decreased serum lipase levels at doses of 1 and 10 mg/kg/h. It significantly lessened the severity of lung edema and improved the microcirculatory environment in the pancreas by increasing now velocity and reducing leukocyte sticking. These results indicate the beneficial effects of gabexate mesilate on pancreatic microcirculation and lung edema in the progression of acute pancreatitis with septic challenge in rats.

Original languageEnglish
Pages (from-to)704-709
Number of pages6
JournalJournal of the Formosan Medical Association
Volume96
Issue number9
StatePublished - 09 1997
Externally publishedYes

Keywords

  • Acute pancreatitis
  • Gabexate mesilate
  • In vivo microscopy
  • Microcirculation
  • Multiple organ dysfunction

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