Therapy of microcirculatory disorders in severe acute pancreatitis: what mediators should we block?
Intensive Care Med
; 28(2): 139-46, 2002 Feb.
Article
em En
| MEDLINE
| ID: mdl-11907656
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.
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Base de dados:
MEDLINE
Assunto principal:
Pancreatite
/
Doenças Vasculares
/
Glicoproteínas da Membrana de Plaquetas
/
Receptores de Superfície Celular
/
Molécula 1 de Adesão Intercelular
/
Receptores Acoplados a Proteínas G
/
Antagonistas dos Receptores de Endotelina
/
Microcirculação
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article