Quantitative evaluation of altered hepatic spaces and membrane transport in fibrotic rat liver.
Four animal models were used to quantitatively evaluate hepatic alterations in this study: (1) a carbon tetrachloride control group (phenobarbital treatment only), (2) a CCl(4)-treated group (phenobarbital with CCl(4) treatment), (3) an alcohol-treated group (liquid diet with alcohol treatment), and (4) a pair-fed alcohol control group (liquid diet only). At the end of induction, single-pass perfused livers were used to conduct multiple indicator dilution (MID) studies. Hepatic spaces (vascular space, extravascular albumin space, extravascular sucrose space, and cellular distribution volume) and water hepatocyte permeability/surface area product were estimated from nonlinear regression of outflow concentration versus time profile data. The hepatic extraction ratio of (3)H-taurocholate was determined by the nonparametric moments method. Livers were then dissected for histopathologic analyses (e.g., fibrosis index, number of fenestrae). In these 4 models, CCl(4)-treated rats were found to have the smallest vascular space, extravascular albumin space, (3)H-taurocholate extraction, and water hepatocyte permeability/surface area product but the largest extravascular sucrose space and cellular distribution volume. In addition, a linear relationship was found to exist between histopathologic analyses (fibrosis index or number of fenestrae) and hepatic spaces. The hepatic extraction ratio of (3)H-taurocholate and water hepatocyte permeability/surface area product also correlated to the severity of fibrosis as defined by the fibrosis index. In conclusion, the multiple indicator dilution data obtained from the in situ perfused rat liver can be directly related to histopathologic analyses.
Hung
Daniel Y
DY
Department of Medicine and Division of Chemical Pathology, University of Queensland, Princess Alexandra Hospital, Woollongabba, Australia.
Chang
Ping
P
Cheung
Kee
K
Winterford
Clay
C
Roberts
Michael S
MS
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002250:Carbon Radioisotopes; D002251:Carbon Tetrachloride; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D013395:Sucrose / Q000493:pharmacokinetics; D013656:Taurocholic Acid / Q000493:pharmacokinetics; D013667:Technetium; D014316:Tritium; D014867:Water / Q000378:metabolism
D000418:Albumins; D002250:Carbon Radioisotopes; D014867:Water; D014316:Tritium; D013395:Sucrose; D013656:Taurocholic Acid; D013667:Technetium; D002251:Carbon Tetrachloride