Vascular clearance by the reticuloendothelial system—measurements using two different-sized albumin colloids

Abstract

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with ¹³³Xe washout technique.

The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08±0.05 vs 0.49±0.02 10⁻²s⁻¹). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/ albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.

In the light of data from morphological and physiological studies of the fenestrated and discontinuous liver sinusoids, the patterns of albumin colloid particle kinetics shown here suggest that smaller particles are partly eliminated by sieving through the fenestrae and also passing the blood-interstitial lymphatic barrier. Nanocoll seems to act more like a large molecule than a particulate substance, at least at high particle doses. The increased nanocoll clearance rate constant following RES activation reflects an increased RES organ mass with an increased RES total organ blood flow, and an increased hepatic particle extraction.

Key Words:

• clearance
• colloid
• liver scintigraphy
• macrophage
• reticuloendothelial system (RES)