AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 2 828-R832, Copyright © 1997 by American Physiological Society
Improved method for single-bolus kinetic measurements using a noncleared reference indicator
G. G. Power and S. Bragg
Center for Perinatal Biology, School of Medicine, Loma Linda University, California 92350, USA.
After intravenous injection of a tracer as a single bolus, its
concentration decreases as it mixes with the plasma, disperses throughout
the circulation, and enters body pools. Kinetic values that are dependent
on early concentrations may be in considerable error because mixing is not
instantaneous throughout the circulation, and this problem is particularly
acute in the mammalian fetus, with its distinctive circulatory pattern. To
minimize this error, a method was developed in which the noncleared
reference tracer 125I-labeled albumin was injected together with a
representative, rapidly cleared metabolite 14C-labeled palmitic acid, and
the former was used to correct for mixing delay. A total of 19
disappearance curves were studied after intravenous injection into seven
near-term fetal sheep. Kinetic values were calculated with and without
correction for mixing delay. Taking account of mixing delay increased the
calculated volume of distribution 41% [from 44 +/- 4 (SE) to 62 +/- 3
ml/kg, P < 0.001], increased plasma clearance rate 13% (from 41 +/- 2 to
47 +/- 1 ml-min-1.kg-1, P < 0.002), decreased the rate constant for
irreversible loss 26% (from 1.05 +/- 0.07 to 0.78 +/- 0.04 min-1, P <
0.001), and increased the calculated effective half-life 26% (0.71 +/- 0.06
to 0.90 +/- 0.05 min, P < 0.001). Thus use of the additional reference
marker significantly altered calculated results and provided values
believed to more accurately describe rapid disappearance from the central
mixing compartment into metabolic pools.
