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 language | English |
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Pages (from-to) | 704-709 |
Number of pages | 6 |
Journal | Journal of the Formosan Medical Association |
Volume | 96 |
Issue number | 9 |
State | Published - 09 1997 |
Externally published | Yes |
Keywords
- Acute pancreatitis
- Gabexate mesilate
- In vivo microscopy
- Microcirculation
- Multiple organ dysfunction