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.
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.
Roberts
M S
MS
Department of Pharamcy, Otago Medical School, Dunedin, New Zealand.
Fraser
S
S
Wagner
A
A
McLeod
L
L
D000818:Animals; D001391:Azo Compounds / Q000378:metabolism*; D002021:Buffers; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005070:Evans Blue / Q000378:metabolism*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000378:metabolism*
D001391:Azo Compounds; D002021:Buffers; D004791:Enzyme Inhibitors; D005070:Evans Blue; D013655:Taurochenodeoxycholic Acid; D013395:Sucrose; D013656:Taurocholic Acid; D008012:Lidocaine; D011433:Propranolol; D009638:Norepinephrine