Obstructive jaundice impairs hepatic sinusoidal endothelial cell function and renders liver susceptible to hepatic ischemia/reperfusion.
OBJECTIVE
Obstructive jaundice is associated with increased surgical morbidity and mortality. While parenchymal injury has been defined in obstructive jaundice, the pathogenesis of hepatic sinusoidal endothelial cell injury in obstructive jaundice is unclear. The aims of this study were to investigate hepatic sinusoidal endothelial cell injury in obstructive jaundice by determining serum hyaluronic acid levels, purine nucleoside phosphorylase/alanine aminotransferase ratios, and hyaluronic acid elimination rate, and also to determine whether hepatic parenchymal cell injury in obstructive jaundice is induced more than in normal liver after hepatic ischemia/reperfusion.


METHODS
Male Wistar rats underwent ligation and division of the common bile duct (obstructive jaundice group) or sham operation (Sham group). Serum hyaluronic acid levels and purine nucleoside phosphorylase/alanine aminotransferase ratios in both groups were examined at intervals up to 21 days after surgery. Hepatic blood flow, permeability, neutrophil accumulation, and hyaluronic acid elimination rates in both groups were measured 14 days after surgery. Changes in serum hyaluronic acid and alanine aminotransferase concentrations were determined after 15 min of hepatic ischemia followed by reperfusion.


RESULTS
Serum hyaluronic acid levels remained elevated after bile duct ligation. Hepatic sinusoidal endothelial cell swelling was observed by electron microscopy, and hepatic permeability was increased 14 days after bile duct ligation in association with neutrophil accumulation. Hepatic blood flow in obstructive jaundice remained unchanged, but hyaluronic acid elimination capacity was less than that in the Sham group. After hepatic reperfusion, the disappearance rate of serum hyaluronic acid in obstructive jaundice was lower, and serum alanine aminotransferase levels were higher than those in the Sham group.


CONCLUSIONS
Our findings suggest that obstructive jaundice impairs sinusoidal endothelial cells and that sinusoidal endothelial cell damage in association with sinusoidal deterioration during obstructive jaundice renders liver susceptible to ischemia/reperfusion relative to normal liver.
Yoshidome
H
H
First Department of Surgery, Chiba University School of Medicine, Chuo, Japan.
Miyazaki
M
M
Shimizu
H
H
Ito
H
H
Nakagawa
K
K
Ambiru
S
S
Nakajima
N
N
Edwards
M J
MJ
Lentsch
A B
AB
D000818:Animals; D002779:Cholestasis / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D004198:Disease Susceptibility; D004727:Endothelium / Q000473:pathology / Q000503:physiopathology; D006820:Hyaluronic Acid / Q000097:blood / Q000378:metabolism; D007511:Ischemia / Q000209:etiology*; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008102:Liver Circulation; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010539:Permeability; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology*
D006820:Hyaluronic Acid; D011683:Purine-Nucleoside Phosphorylase