Summary
Heparin radiolabelled with 125I was given intravenously to intact, bilaterally nephrectomised or completely hepatectomised
rats in the presence and absence of 1 mg unlabelled heparin/kg. Plasma samples were
collected and analysed by gel filtration chromatography and affinity chromatography
on Polybrene-Sepharose, which binds sulphated glycosaminoglycans. Radiolabel in the
plasma was associated with both intact heparin and fully desulphated macromolecular
carbohydrate chains. Levels of intact heparin in plasma from control rats decreased
with time at both doses with a concomitant increase in desulphated material. Livers
accumulated the greatest amounts of radiolabel on a per organ basis. Hepatectomy both
increased levels of radiolabel in plasma and decreased amounts of desulphated heparin
produced, indicating that the liver was the major site of desulphation. Even after
removal of the liver, the desulphated metabolite comprised approximately 15% of radiolabelled
material at all times and doses, suggesting an additional site of GAG desulphation
which may be the vascular endothelium. The kidneys contributed significantly to in vivo desulphation of heparin only at the high dose.
