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[Endothelin receptor block in acute pancreatitis--improvement of microcirculation and decrease of capillary
1Chirurgische Klinik I, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin.
Langenbecks Archiv Fur Chirurgie. Supplement. Kongressband. Deutsche Gesellschaft Fur Chirurgie. Kongress
|October 2, 2003
Summary
A novel endothelin-1 receptor antagonist (ET-RA) therapy significantly improves survival in acute necrotizing pancreatitis (ANP) by stabilizing capillary permeability and reducing fluid loss, thereby counteracting systemic complications.
Area of Science:
- Biomedical Research
- Gastroenterology
- Pharmacology
Background:
- Acute necrotizing pancreatitis (ANP) is a severe condition with high mortality.
- Previous studies indicated endothelin-1 receptor antagonists (ET-RA) reduce ANP mortality in rats.
- ET-RA's benefit was linked to reduced fluid sequestration, suggesting a systemic effect.
Purpose of the Study:
- To investigate the systemic effects of a specific ET-1 antagonist, LU-135252, in ANP.
- To evaluate ET-RA's impact on capillary function, fluid balance, and organ function in ANP.
- To confirm if ET-RA counteracts systemic microcirculatory disorders in ANP.
Main Methods:
- Therapy with LU-135252 initiated 6 hours post-disease onset in a rat ANP model.
- Assessment of capillary blood flow, density, and permeability in the pancreas and colon.
- Monitoring of fluid losses, ascites, and renal and respiratory function.
Main Results:
- ET-RA stabilized increased capillary permeability in the pancreas and colon.
- Treatment reduced ascites and improved renal and respiratory function.
- ET-RA enhanced reduced capillary blood flow and density in affected organs.
Conclusions:
- ET-RA therapy effectively counteracts systemic microcirculatory dysfunction in ANP.
- Stabilization of capillary permeability and reduced fluid leakage contribute to improved outcomes.
- These findings support ET-RA as a potential therapeutic strategy for severe pancreatitis.