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Has anyone done ICG (Indocyanine Green) modeling with SAAM II to
determine hepatic blood flow and thus cardiac output?
I am currently looking at ICGs performed at 3 different times during
the course of a PK/PD study to evaluate the drugs effect on cardiac
output if any.
Louis P. Blatzheim
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I have used dyes such as ICG and BSP to determine regional blood flow under
many conditions and in different regions (cardiac output, liver, kidneys,
hind quarters, etc) in sheep. The Law of Conservation of Matter applies
without exception. Several points:
1. these dyes are incompletely extracted and variably by the liver,
therefore hepatic extraction or flux needs to be measured for determination
of regional blood flow using the Fick principle. Assumption of dye clearance
= regional flow is fraught with danger.
2. there is not a lot of modeling necessary to determine the regional blood
flow: if administered by bolus then an algorithm for AUC is it; if by
infusion then serial concentrations are enough. However, as noted above,
both inflowing and outflowing concentrations may be needed.
3. non-linear kinetics are a vexation - so watch carefully - they may occur
as a consequence of the PD effect of the operant condition.
4. of all the discussion about flow and perfusion think carefully - when the
dyes are used for indicator dilution they are estimating flow, when used for
Fick calculations they are estimating perfusion but recording it as flow.
Flow is a fraction of cardiac output directed INTO a defined region,
perfusion is THROUGH a region. It is not possible to have blood flowing
into a region that is blocked distally - where does the blood flow to?
5. if you haven't already done so then have a look through the classical
physiology of Hamilton and others of the 1920s. A very readable secondary
source of immense value is Lassen and Perl "Tracer Kinetic Methods in
Medical Physiology" Raven Press 1979.
6. On the issue of substances cleared by lung discussed recently the issues
can be studied systemically or in the respiratory system for example as in
our recent offering Reid MA, Mather LE, Ilsley AH, Runciman WB. Comparison
of the respiratory and systemic kinetics of nitrous oxide in the sheep.
Acta Anaesthesiol Scandinav 40: 809-814:(1996). Even with a gas such as
nitrous oxide, its whole body mass balance is not accounted for by lung
7. Substances with very high clearances can be subject to multiple sites of
clearance - or o high affinity tissue binding that masquerades as
clearance. Examples of our offerings in coming to grips with these issues:
Upton RN, Runciman WB, Mather LE, Carapetis RJ, McLean CF. The use of mass
balance principles to determine lignocaine and procainamide disposition in
the hindquarters of the sheep. J Pharmacokin Biopharm 16: 31-40 (1988) and
Upton RN, Mather LE, Runciman WB, McLean CF, Carapetis RJ. The uptake and
elimination of chlormethiazole, meperidine and minaxolone in the
hindquarters of the sheep: application of mass balance principles. J Pharm
Sci 80: 108-112 (1991).
The take home message - don't assume, measure!
Professor of Anaesthesia and Analgesia (Research)
University of Sydney at Royal North Shore Hospital
St Leonards NSW 2065 Australia
Ph +61 2 9926 8420; Fax +61 2 9906 4079
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Copyright 1995-2010 David W. A. Bourne (email@example.com)