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- Title
Therapy of microcirculatory disorders in severe acute pancreatitis: what mediators should we block?
- Authors
Eibl, Guido; Buhr, Heinz J.; Foitzik, Thomas
- Abstract
Objective: To compare the effect of different vasoactive mediator antagonists in the same model of severe acute pancreatitis (AP) and to evaluate whether combinations of the agents exhibit synergistic effects. Design: Prospective experimental study. Setting: Microcirculation and pancreas research laboratory at an university hospital. Participants: Hundred eighty anesthetized male Sprague-Dawley rats. Interventions: Six hours after inducing AP by intra-ductal bile salt infusion and i.v. cerulein in 168 rats, these were randomized for therapy with (1) saline, (2) endothelin receptor antagonist (ET-RA), (3) platelet activating factor receptor antagonist (PAF-RA), (4) intercellular adhesion molecule-1 antibody (ICAM-1-AB) or different combinations (5–7). After 24 h the animals underwent a second laparotomy for intra-vital microscopic determination of pancreatic and colonic capillary permeability, blood flow and leukocyte-endothelial interaction. Results: AP induction decreased capillary blood flow and increased permeability and leukocyte rolling. ET-RA, PAF-RA and ICAM-1-AB decreased capillary permeability, increased blood flow and reduced leukocyte rolling. ET-RA was most effective in decreasing capillary permeability in both organs as well as in increasing pancreatic capillary blood flow. Combining vasoactive mediator blockers did not further improve target parameters. Conclusions: This study supports previous observations that ET-RA, PAF-RA and ICAM-1-AB improve microcirculation in AP and that ET-RA is more effective than PAF-RA or ICAM-1-AB, especially in counteracting capillary leakage. Although this may suggest that they act through different mechanisms, antagonist combinations failed to improve microcirculation further. We conclude that ET-RA is the most promising candidate for a clinical trial to reduce capillary leakage in patients with AP.
- Subjects
PANCREATITIS; MICROCIRCULATION disorders; VASODILATORS; CARDIOVASCULAR agents; ENDOTHELINS; CRITICAL care medicine
- Publication
Intensive Care Medicine, 2002, Vol 28, Issue 2, p139
- ISSN
0342-4642
- Publication type
Article
- DOI
10.1007/s00134-001-1194-1