The effect of intraportal prostaglandin E1 on adhesion molecule expression, inflammatory modulator function, and histology in canine hepatic ischemia/reperfusion injury.
BACKGROUND
Prostaglandin E1 (PGE1) is known to protect the liver from I/R, however, the mechanism of cytoprotection is not well understood. This study investigates the effect of intraportal infusion of PGE1 in a warm liver ischemia/reperfusion (I/R) model on cytokines, adhesion molecules and liver structure.


METHODS
Twenty dogs underwent laparotomy under general anesthesia. PGE1 (0.02 microg\kg\min) was perfused through the portal vein in the PGE1 group (n = 10), or a similar volume of Ringer's solution in the control group (n = 10) for 15 min. Liver ischemia was induced by hepatic artery and portal vein occlusion and PGE1 was infused via the portal vein for 60 min. The occlusion was released and PGE1 infusion recommenced for 30 min. Blood and liver biopsies were sampled at baseline, 60 min ischemia, and 30 min reperfusion and assessed for transaminases, cytokines, adhesion molecules, and electron microscopy.


RESULTS
PGE1 infusion significantly reduced transaminases TNF-alpha, sICAM-1, sP-selectin, and sE-selectin on ischemia and reperfusion. PGE1 reduced hepatocytic degeneration, portal and central ICAM-1 expression, central and sinusoidal VCAM-1 expression, portal and central P-selectin expression, and portal and sinusoidal E-selectin expression on reperfusion.


CONCLUSIONS
Intraportal PGE1 infusion reduced I/R injury and was associated with down-regulation of ICAM-1, VCAM-1, P-selectin, and E-selectin on reperfusion.
Hafez
Tariq
T
Department of Surgery, Royal Free and University College Medical School, University College London, London, United Kingdom.
Moussa
Mona
M
Nesim
Iris
I
Baligh
Nadia
N
Davidson
Brian
B
Abdul-Hadi
Ahmed
A
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004285:Dogs; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000473:pathology / Q000648:ultrastructure; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D019007:P-Selectin / Q000378:metabolism; D011169:Portal Vein; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D018836:Inflammation Mediators; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D018799:Intercellular Adhesion Molecule-1; D000527:Alprostadil