Effects of hepatic blood flow on hepatic ethanol kinetics measured in cats and predicted from the parallel tube model.
In cats anesthetized with pentobarbital, a long-circuit technique was used to measure hepatic blood flow while portal flow was varied from 0 to 300% of normal in random steps. Arterial, portal, and hepatic venous blood samples were analyzed for ethanol concentrations during continuous infusion of ethanol (20 mumol/(min.kg body weight) into the reservoir. Measured values for logarithmic mean sinusoidal ethanol concentration, hepatic venous ethanol concentration, hepatic ethanol uptake, and ethanol extraction were compared with the values predicted by the parallel tube model for hepatic uptake of substrates using Vmax and Km determined in each cat at the start of the experiment. Measured and predicted values were very similar at all blood flows above 65% control, but statistical regression analysis indicated a small but highly significant deviation of the measured values from the predicted values. At low flows, measured values of logarithmic mean sinusoidal and hepatic venous concentrations markedly exceeded the predicted values in most cats. The results indicate that the parallel tube model, which assumes all sinusoids are identical and equally perfused, provides a useful approximation for the effects of hepatic blood flow on hepatic ethanol kinetics except at low flows. However, there appears to be a significant degree of sinusoidal heterogeneity that results in a better fit to the distributed model. Our previously reported data for hepatic galactose uptake followed a similar pattern when reanalyzed in this more rigorous way.
Department of Pharmacology, University of Manitoba, Winnipeg, Canada.
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CV
Greenway
D000818:Animals; D002415:Cats; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D008954:Models, Biological; D010477:Perfusion
D000431:Ethanol