Biliary retention in a chronic choledocho-venous fistula in the rat: induction of portal hypertension but not of biliary cirrhosis.
In this study we investigated whether the retention of compounds which are excreted into the bile could contribute to portal hypertension in secondary biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13 of the animals had biochemical evidence of partial obstruction. Microsomal function, as measured by the aminopyrine breath test, was decreased in all animals with biliary retention while microsomal cytochrome P-450 content was decreased only in rats with evidence of obstruction. All animals with biliary retention with or without partial obstruction had portal hypertension. Animals with biliary retention and partial obstruction had hypercholeresis but decreased bile salt excretion. All animals with a chronic catheter in the biliary tree had a loss of the negative permselectivity of the sinusoidal-canalicular barrier and decreased maximal bile secretory pressure. Only animals with biochemical evidence of obstruction had moderate fibrosis and ductular proliferation as determined by stereological techniques. Unexpectedly, morphometric analysis also revealed an increase in hepatocyte mass induced by biliary retention. We conclude that bile contains a compound(s) which induces portal hypertension. This putative substance is neither bilirubin nor a bile acid since portal hypertension was also observed in animals with biliary retention without obstructive signs.
Zimmermann
H
H
Department of Clinical Pharmacology, University of Berne, Switzerland.
Reichen
J
J
Sägesser
H
H
Tenisch
B
B
Zimmermann
A
A
D000632:Aminopyrine / Q000032:analysis; D000818:Animals; D001658:Biliary Fistula; D001660:Biliary Tract Diseases / Q000150:complications* / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D001944:Breath Tests; D002908:Chronic Disease; D006975:Hypertension, Portal / Q000209:etiology* / Q000378:metabolism; D050356:Lipid Metabolism; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014680:Veins
D000632:Aminopyrine; D001663:Bilirubin