M Weiss1, L N Ballinger, M S Roberts. 1. Department of Pharmacology, Martin Luther University Halle-Wittenberg, Germany. michael.weiss@medizin.uni-halle.de
Abstract
BACKGROUND/AIMS: Liver clearance models are based on information (or assumptions) on solute distribution kinetics within the microvasculatory system. The aim was to study albumin distribution kinetics in regenerated livers and in livers of normal adult rats. METHODS: A novel mathematical model was used to evaluate the distribution space and the transit time dispersion of albumin in livers following regeneration after a two-thirds hepatectomy compared to livers of normal adult rats. Outflow curves of albumin measured after bolus injection in single-pass perfused rat livers were analyzed by correcting for the influence of catheters and fitting a long-tailed function to the data. RESULTS: The curves were well described by the proposed model. The distribution volume and the transit time dispersion of albumin observed in the partial hepatectomy group were not significantly different from livers of normal adult rats. CONCLUSIONS: These findings suggest that the distribution space and the transit time dispersion of albumin (CV2) is relatively constant irrespective of the presence of rapid and extensive repair. This invariance of CV2 implies, as a first approximation, a similar degree of intrasinusoidal mixing. The finding that a sum of two (instead of one) inverse Gaussian densities is an appropriate empirical function to describe the outflow curve of vascular indicators has consequences for an improved prediction of hepatic solute extraction.
BACKGROUND/AIMS: Liver clearance models are based on information (or assumptions) on solute distribution kinetics within the microvasculatory system. The aim was to study albumin distribution kinetics in regenerated livers and in livers of normal adult rats. METHODS: A novel mathematical model was used to evaluate the distribution space and the transit time dispersion of albumin in livers following regeneration after a two-thirds hepatectomy compared to livers of normal adult rats. Outflow curves of albumin measured after bolus injection in single-pass perfused rat livers were analyzed by correcting for the influence of catheters and fitting a long-tailed function to the data. RESULTS: The curves were well described by the proposed model. The distribution volume and the transit time dispersion of albumin observed in the partial hepatectomy group were not significantly different from livers of normal adult rats. CONCLUSIONS: These findings suggest that the distribution space and the transit time dispersion of albumin (CV2) is relatively constant irrespective of the presence of rapid and extensive repair. This invariance of CV2 implies, as a first approximation, a similar degree of intrasinusoidal mixing. The finding that a sum of two (instead of one) inverse Gaussian densities is an appropriate empirical function to describe the outflow curve of vascular indicators has consequences for an improved prediction of hepatic solute extraction.
Authors: Alessandra Warren; Slawomir Chaberek; Kazimierz Ostrowski; Victoria C Cogger; Sarah N Hilmer; Robert S McCuskey; Robin Fraser; David G Le Couteur Journal: Microcirculation Date: 2008-04 Impact factor: 2.628