title: [14C]urea and 58Co-EDTA as reference indicators in hepatic multiple indicator dilution studies.
abstract: The space distribution and the processes underlying uptake of tracer substrate may be appraised by the multiple indicator dilution technique, after the simultaneous injection of noneliminated vascular (51Cr-labeled red blood cells), extracellular (125I-labeled albumin and [14C]sucrose for high and low molecular weight interstitial space, respectively), and cellular (3H2O) indicators and tracer substrate. When tracer substrates and/or their metabolites containing 14C or 3H labels are being studied, it becomes necessary to find substitutions for the similarly labeled noneliminated indicators. In red blood cell-perfused rat livers, 58Co-EDTA is found to be a good replacement for the low molecular weight interstitial reference; it has a space distribution indistinguishable from that for [14C]sucrose. [14C]urea and 3H2O, which distribute similarly in red blood cells, have similar outflow dilution profiles. With corrections for minor deviations in recovery [a ratio of 0.936 +/- 0.024 (SD)] and transit time [a ratio of 0.962 +/- 0.008 (SD)], the cellular water space can be closely approximated from the [14C]-urea curve. 58Co-EDTA and [14C]urea are reasonable substitutes for [14C]sucrose and 3H2O, respectively, in multiple indicator dilution liver perfusion studies for investigating transfer and removal characteristics of tracer substrates.
authors.affiliation: Faculty of Pharmacy, University of Toronto, Ontario, Canada.
authors.forename: K S
authors.initials: KS
authors.lastname: Pang
authors.forename: F
authors.initials: F
authors.lastname: Barker
authors.forename: A J
authors.initials: AJ
authors.lastname: Schwab
authors.forename: C A
authors.initials: CA
authors.lastname: Goresky
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D003035:Cobalt; D003037:Cobalt Radioisotopes; D004492:Edetic Acid; D008099:Liver / Q000502:physiology*; D008102:Liver Circulation; D008297:Male; D010477:Perfusion; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose; D014316:Tritium; D014508:Urea
chemical_list: D002250:Carbon Radioisotopes; D003037:Cobalt Radioisotopes; D014316:Tritium; C028222:cobalt-ethylenediamine tetraacetic acid chelate; D003035:Cobalt; D013395:Sucrose; D014508:Urea; D004492:Edetic Acid