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Residence time distributions of solutes in the perfused rat liver using a dispersion model of hepatic elimination: 2. Effect of pharmacological agents,retrograde perfusions,and enzyme inhibition on evans blue,sucrose, water,and taurocholate
Authors:Michael S. Roberts  Sharon Fraser  Andrew Wagner  Lyndsay McLeod
Affiliation:(1) Department of Pharmacy, Otago Medical School, Dunedin, New Zealand;(2) Present address: Departments of Pharmacy and Medicine, University of Queensland, 4067 St. Lucia, Queensland, Australia;(3) School of Pharmacy, University of Tasmania, Hobart, Australia;(4) Department of Physiology, University of Tasmania, Hobart, Australia
Abstract:
The effect of altered physiological conditions on the residence time distributions of sucrose, water, and taurocholate in the rat liver were studied using a bolus injection and quantifying fraction of total outflow per ml-time profiles. Retrograde perfusions increased the residence times of sucrose and water markedly and were associated with very low hepatic availabilities for taurocholate. Resistance by the inlet sinusoids sphincters, which become outlet sphincters during retrograde perfusions, is suggested as the explanation for the observation. Infusions of noradrenaline, propranolol, and lidocaine resulted in relatively small changes in the mean residence times for sucrose and water with no apparent relationship existing between the efficiency number of taurocholate and volumes of either water or sucrose. Taurochenodeoxycholate resulted in an increase in the availability and mean residence time for taurocholate relative to no infusion.This study was supported by the National Health and Medical Research Council of Australia and the Dean's MRC (NZ) Fund.
Keywords:liver metabolism  hepatic models  residence time distribution  dispersion model  drug infusions  enzyme inhibition  retrograde perfusion  rat liver
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