Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 2. Hemodynamic and drug disposition studies.
We assessed hepatic functions and systemic and splanchnic hemodynamics in a new model of hepatic sinusoidal fibrosis. Fibrosis was induced by the simultaneous administration for 8 weeks of diethyl-stilbestrol (DES) (10 mg twice weekly, subcutaneously) and cholesterol-supplemented diet (1%) in rabbits. A marked and progressive impairment of hepatic function was observed during the 8 weeks of treatment with a significant decrease in indocyanine green (ICG) systemic clearance (-89%; P < .001) and aminopyrine elimination (-69%; P < .001). In fibrotic animals, hyperdynamic circulation was found with an increased cardiac output (+73%, P < 0.01) and a decreased peripheral vascular resistance (-50%; P < .005), as evaluated by the microsphere technique in animals that were awake. The total portal venous inflow was not significantly modified in fibrotic rabbits. However, since there was a marked increase in the liver weight, the portal venous inflow was significantly decreased when expressed per gram of liver weight (-30%; P < .05). In contrast, the hepatic artery blood flow was markedly increased, even when expressed per gram of liver weight (+95%; P < .01). Portal pressure was significantly increased in treated rabbits (from 7.4 +/- .4 to 14.4 +/- .6 mm Hg, P < .01). This new experimental model could prove useful to evaluate the influence of extensive perisinusoidal fibrosis on exchanges between plasma and hepatocytes, particularly of protein-bound substances.
Mastaï
R
R
Centre de Recherche Clinique André-Viallet, Hôpital Saint-Luc, University of Montreal, Canada.
Laganière
S
S
Wanless
I R
IR
Giroux
L
L
Rocheleau
B
B
Huet
P M
PM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002791:Cholesterol, Dietary; D004054:Diethylstilbestrol; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011169:Portal Vein / Q000187:drug effects / Q000503:physiopathology; D011817:Rabbits
D002791:Cholesterol, Dietary; D004054:Diethylstilbestrol