Initial plasma disappearance and distribution volume of [¹³¹l]albumin and [¹²⁵l]fibrinogen in man

Abstract

The simultaneous plasma disappearance curves of albumin and fibrinogen were recorded in eight normal subjects from 10 to 60 min following intravenous injection. Additional samples were taken at 3, 4, 5, 6 and 7 min. The initial distribution volume (IDV) of albumin calculated by semilogarithmic extrapolation to zero time was 5.56% (range 3.73-8.53) larger than that of fibrinogen, denoting an initial high-rate function of albumin efflux extending from zero to about 10 min after tracer injection. The following slower phase of the albumin curve from 10 to 60 min was found to be similar to the so-called transcapillary escape rate (TER) of single-tracer experiments. By introducing the value Cp(0) (i.e. the estimated curve height at t = 0, from the injected amount of albumin tracer divided by the IDVf), the entire initial part of the albumin curves was analysed. From this analysis the mean value of 0.0135 +/- 0.0038 min-1 was determined for initial slope, corresponding to a whole-body unidirectional albumin efflux [j(0)] of 0.0572 +/- 0.0160 ml 100 g-1 min-1. The result is about 16 times higher than normal estimates of total lymphatic albumin return, indicating a huge backflux of interstitial albumin at the whole-body capillary level. Both phases of efflux seem to reflect uptake in a variety of peripheral tissues, and the hypothesis that the second phase (TER) expresses the initial slope of albumin escape into non-liver tissues is not substantiated. Based on the difference in IDV of the tracers demonstrated, the uncritical use of albumin as a plasma volume marker is not justified.

Plasma volume in acute hypoxia: comparison of a carbon monoxide rebreathing method and dye dilution with Evans' blue

“…In the presence of a hypoxia-induced increase in the albumin distribution volume, methods using tagged albumin may be expected to result in an overestimation of plasma volume. This would add further to the overestimation induced by the early escape of albumin into the small perivascular compartment as has been reported by Bent-Hansen (1989, 1991, and would also blunt the detection of an actual decrease in plasma volume in hypoxia. In this study, measurements of the overall albumin distribution volume were related to measurements of haemoglobin distribution volume by the use of a CO rebreathing method.…”

“…Values in both environments were higher than those that have been measured normally using Ilabelled albumin in resting healthy subjects (Parving 1972;Parving and Gyntelberg 1973;Bent-Hansen 1989;Hansen et al 1994). By simultaneous measurements of TER Alb with 131 I and Evans' blue in the same subjects, it has been demonstrated directly that the use of Evans' blue results in higher values of TER Alb , probably due to phagocytosis of partly denaturated T-1824-albumin complexes (Parving 1972).…”

“…In normal conditions, it has been found that the distribution volume of injected albumin slightly overestimates the plasma volume due to an early escape of albumin into a small perivascular compartment with rapid back-diusion (Bent-Hansen 1989). Beyond this small perivascular compartment close to the exterior endothelial membrane is a larger interstitial compartment that has been shown to communicate with the lymphatic system (Bent -Hansen 1989-Hansen , 1991. After a short rapid decay representing the exchange with the ®rst compartment, the albumin disappearance curve has shown a steady protracted phase representing the overall transvascular albumin clearance through the interstitial compartment (Bent-Hansen 1991).…”

“…It has been suggested that the use of albumin and Evans' blue as plasma volume markers is not justi®ed due to the dierence in the initial distribution volume compared with tracers larger than albumin (Bent-Hansen 1989). In normal conditions, it has been found that the distribution volume of injected albumin slightly overestimates the plasma volume due to an early escape of albumin into a small perivascular compartment with rapid back-diusion (Bent-Hansen 1989).…”

“…After a short rapid decay representing the exchange with the ®rst compartment, the albumin disappearance curve has shown a steady protracted phase representing the overall transvascular albumin clearance through the interstitial compartment (Bent-Hansen 1991). After the introduction of an intravenous bolus of labelled albumin, the rate of the second phase has been used to provide a measure of the whole body transcapillary escape rate of albumin (TER Alb ); (Parving and Gyntelberg 1973;Bent-Hansen 1989, 1991.…”