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[14C]urea and 58Co-EDTA as reference indicators in hepatic multiple indicator dilution studies.
K S Pang1, F Barker, A J Schwab
1Faculty of Pharmacy, University of Toronto, Ontario, Canada.
The American Journal of Physiology
|July 1, 1990
Summary
Researchers found suitable replacements for radioactive tracers in liver perfusion studies. Cobalt-58-ethylenediaminetetraacetic acid (58Co-EDTA) and Carbon-14-urea ([14C]urea) can substitute for existing labels, improving the study of substrate uptake and removal.
Area of Science:
- Physiology
- Biochemistry
- Pharmacology
Background:
- The multiple indicator dilution technique is crucial for appraising tracer substrate uptake and distribution in biological systems.
- Existing methods often rely on radioactive labels that can interfere with the study of certain tracer substrates and their metabolites.
- There is a need for non-interfering reference indicators in multiple indicator dilution studies, particularly in liver perfusion models.
Purpose of the Study:
- To identify suitable non-radioactive or differently-labeled substitutes for commonly used indicators in multiple indicator dilution liver perfusion studies.
- To evaluate the efficacy of 58Co-EDTA as a replacement for low molecular weight interstitial space indicators like [14C]sucrose.
- To assess the suitability of [14C]urea as a substitute for cellular water indicators such as 3H2O in liver perfusion experiments.
Main Methods:
- Simultaneous injection of vascular, extracellular (high and low molecular weight), and cellular indicators along with tracer substrates into red blood cell-perfused rat livers.
- Comparison of the distribution and outflow dilution profiles of potential substitute indicators (58Co-EDTA, [14C]urea) against established indicators ([14C]sucrose, 3H2O).
- Mathematical corrections for minor deviations in indicator recovery and transit time were applied.
Main Results:
- 58Co-EDTA demonstrated a space distribution indistinguishable from [14C]sucrose, validating its use as a low molecular weight interstitial reference.
- [14C]urea and 3H2O exhibited similar distribution and outflow dilution profiles in red blood cells.
- Cellular water space could be accurately approximated using the [14C]urea curve after applying corrections for recovery and transit time.
Conclusions:
- 58Co-EDTA and [14C]urea are effective and suitable substitutes for [14C]sucrose and 3H2O, respectively, in multiple indicator dilution liver perfusion studies.
- These substitutions facilitate the investigation of transfer and removal characteristics of tracer substrates without interference from similar labels.
- The findings enhance the versatility and applicability of the multiple indicator dilution technique in liver physiology and drug metabolism research.