Adrenomedullin treatment abolishes ileal mucosal hypoperfusion induced by Staphylococcus aureus alpha-toxin--an intravital microscopic study on an isolated rat ileum.
OBJECTIVE
Disturbances of intestinal microcirculation associated with sepsis and septic shock result in diminished mucosal oxygenation. Tissue hypoxia as well as mediator formation may lead to intestinal mucosa dysfunction. As a consequence, bacteria and their products as well as gut-derived inflammatory mediators may further perpetuate septic and inflammatory events. Adrenomedullin is produced in the mucosa of the gastrointestinal tract and has been shown to improve survival in experimental sepsis. Using pore-forming Staphylococcus aureus alpha-toxin as a potent initiator of inflammatory reactions, we tested the hypothesis that exogenously added adrenomedullin improves ileal mucosal perfusion.


METHODS
Prospective, experimental study.


METHODS
University laboratory.


METHODS
Isolated perfused ileum from male Sprague-Dawley rats


METHODS
Adrenomedullin treatment of S. aureus alpha-toxin infused ileum.


RESULTS
An infusion of alpha-toxin (0.05 microg/mL) induced a significant decrease of red blood cell velocity in villus terminal arterioles from 1.7 to 0.7 mm/sec assessed by intravital microscopy. This was accompanied by a significant reduction of mucosal hemoglobin oxygenation from 71.8% to 17.5% and impaired oxygen uptake. At constant bulk flow and oxygen delivery, these data indicate a redistribution of blood perfusion away from mucosa. Subsequent intervention with 0.1 microM adrenomedullin redistributed blood flow back toward the mucosa, causing an improvement of mucosal hemoglobin oxygenation and of organ oxygen uptake.


CONCLUSIONS
These data suggest that exogenously added adrenomedullin protects ileum mucosa by diminishing alpha-toxin-induced microcirculatory disturbances. Further investigations will have to clarify the therapeutic potential of adrenomedullin in sepsis-related gut dysfunction.
Brell
Bernhard
B
Department of Internal Medicine/Infectious Diseases, Charité-University Medicine Berlin, Berlin, Germany.
Hippenstiel
Stefan
S
Dávid
István
I
Pries
Axel R
AR
Habazettl
Helmut
H
Schmeck
Bernd
B
Suttorp
Norbert
N
Temmesfeld-Wollbrück
Bettina
B
D053607:Adrenomedullin; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001783:Blood Flow Velocity / Q000187:drug effects; D006460:Hemolysin Proteins; D007082:Ileum / Q000098:blood supply* / Q000473:pathology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D010455:Peptides; C021091:staphylococcal alpha-toxin; D053607:Adrenomedullin