Document Detail

Adrenomedullin reduces Staphylococcus aureus alpha-toxin-induced rat ileum microcirculatory damage.
MedLine Citation:
PMID:  15818111     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Increased microvascular permeability and perfusion mismatch are hallmarks of sepsis or septic shock. The intestinal mucosa is very sensitive to tissue hypoxia. Intestinal mucosa dysfunction may allow translocation of bacteria and their products, thereby perpetuating sepsis and inflammation. Staphylococcus aureus alpha-toxin is a major pathogenicity determinant of this bacterium, provoking cardiovascular collapse. Current evidence suggests that the endogenous peptide adrenomedullin stabilizes circulatory homeostasis in systemic inflammatory response. Using alpha-toxin as a well-defined strong initiator of an inflammatory reaction, we tested the hypothesis that exogenously applied adrenomedullin stabilizes gut microcirculation. DESIGN: Prospective, experimental study. SETTING: Research laboratory at a university hospital. SUBJECTS: Isolated, perfused ileum from male Sprague-Dawley rats and human umbilical vein endothelial cells. INTERVENTIONS: Administration of S. aureus alpha-toxin before or after infusion of adrenomedullin. MEASUREMENTS AND MAIN RESULTS: Injection of a bolus of 1 microg of alpha-toxin in the superior mesenteric artery in a constant-flow, blood-perfused preparation of rat ileum increased perfusion pressure and relative hemoglobin concentration and decreased mucosal hemoglobin oxygen saturation. Continuous infusion of adrenomedullin (0.1 micromol/L) significantly reduced these alpha-toxin-related effects. Severe microvascular hyperpermeability observed in alpha-toxin-exposed ileum was abolished by adrenomedullin pretreatment. In addition, adrenomedullin blocked alpha-toxin-induced endothelial myosin light chain phosphorylation, endothelial cell contraction, and subsequent loss of endothelial barrier function in vitro. Treatment of alpha-toxin (infusion of 0.05 microg/mL)-exposed ileum with adrenomedullin (0.1 micromol/L) started 10 mins after onset of toxin application also significantly reduced superior mesenteric artery pressure and permeability increase. CONCLUSIONS: In summary, these data suggest that exogenous adrenomedullin protects ileum by reducing alpha-toxin-induced microcirculatory disturbances and by stabilizing endothelial barrier function.
Bernhard Brell; Bettina Temmesfeld-Wollbrück; Iris Altzschner; Eckehard Frisch; Bernd Schmeck; Andreas C Hocke; Norbert Suttorp; Stefan Hippenstiel
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Critical care medicine     Volume:  33     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-08     Completed Date:  2005-05-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  819-26     Citation Subset:  AIM; IM    
Department of Internal Medicine/Infectious Diseases, University Medicine Berlin, Berlin, Germany.
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MeSH Terms
Anti-Infective Agents / administration & dosage*
Bacterial Toxins / toxicity*
Capillary Permeability / drug effects
Disease Models, Animal
Ileum / blood supply*,  drug effects
Infusions, Intravenous
Intestinal Mucosa / blood supply,  drug effects,  physiopathology
Microcirculation / drug effects,  physiopathology
Microfilaments / metabolism
Myosin Light Chains / metabolism
Peptides / administration & dosage*
Phosphorylation / drug effects
Prospective Studies
Rats, Sprague-Dawley
Staphylococcus aureus*
Treatment Outcome
Reg. No./Substance:
0/Anti-Infective Agents; 0/Bacterial Toxins; 0/Myosin Light Chains; 0/Peptides; 148498-78-6/Adrenomedullin

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