Dynamic in vivo observation of villus microcirculation during small bowel autotransplantation: effects of endothelin-A receptor inhibition.
BACKGROUND
The aims of this study were to characterize the structural and microcirculatory changes in single intestinal villi during ischemia and reperfusion and determine the site of action of endothelin (ET)-A receptor inhibition during compromised mucosal perfusion.


METHODS
Small bowel autotransplantation was performed in anesthetized dogs. One group was treated with the ET-A receptor antagonist ETR-p1/fl peptide. The epithelial thickness and villus microcirculatory parameters were observed by orthogonal polarization spectral imaging; the leukocyte-endothelial cell interactions were quantified with fluorescence videomicroscopy.


RESULTS
Sixty-minute cold ischemia and 240-min reperfusion induced a decrease in villus functional capillary density and leukocyte-endothelial cell interactions. The epithelial layer was gradually removed, but denuded villi were not observed. ET-A receptor inhibition reduced the leukocyte adherence and attenuated epithelial exfoliation and the decrease in villus functional capillary density.


CONCLUSIONS
ET-A receptor activation mediates microvascular dysfunction through precapillary blockades and leukocyte-endothelial cell interactions after cold ischemia and reperfusion in the canine small bowel.
Wolfárd
Antal
A
Institute of Surgical Research and Department of Surgery, University of Szeged, Szent-Györgyi Albert Medical Center, H-6720 Szeged, Hungary.
Szalay
László
L
Kaszaki
József
J
Sahin-Tóth
Gábor
G
Vangel
Róbert
R
Balogh
Adám
A
Boros
Mihály
M
D000818:Animals; D002196:Capillaries / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D015925:Cryopreservation; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins; D007421:Intestine, Small / Q000098:blood supply* / Q000637:transplantation*; D007511:Ischemia / Q000473:pathology; D007962:Leukocytes / Q000502:physiology; D008833:Microcirculation; D008871:Microvilli / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology*; D015427:Reperfusion Injury / Q000473:pathology; D014182:Transplantation, Autologous
C109027:ETR-p1-f1 antisense peptide; D065128:Endothelin Receptor Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin