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Research Article Free access | 10.1172/JCI116095

Hepatic uptake of a modified low molecular weight heparin in rats.

G Stehle, E A Friedrich, H Sinn, A Wunder, J Harenberg, C E Dempfle, W Maier-Borst, and D L Heene

First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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First Department of Medicine, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.

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Published November 1, 1992 - More info

Published in Volume 90, Issue 5 on November 1, 1992
J Clin Invest. 1992;90(5):2110–2116. https://doi.org/10.1172/JCI116095.
© 1992 The American Society for Clinical Investigation
Published November 1, 1992 - Version history
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Abstract

Fractionated and unfractionated heparins are widely used as antithrombotic agents. Because of their heterogeneous composition, it is difficult to study the pharmacokinetics of these drugs. We now report on a new method for labeling low molecular weight heparins with 131I by binding tyramine to the anhydromannose end of the molecules. We examined the pharmacokinetics of the compound by intravenous injection of 131I-tyramine-heparin into Wistar rats. About 18% of the activity was found in the liver, whereas 33% was detected in urine. Biological activity in terms of Factor Xa inhibition was measurable. Since evidence from cell culture experiments implies that reticuloendothelial cell system receptors might be involved in heparin metabolism, maleylated BSA, a substance known to block scavenger receptors, was injected before the radiolabeled heparin compound. The liver uptake was reduced from 17.4 to 4.8%. Injection of unfractionated heparin before tracer application caused a considerable increase in urine excretion of the tracer substance. To our knowledge, this is the first report that liver uptake of heparins is linked to scavenger receptor mediated mechanisms in vivo. This interaction of heparins with scavenger receptors might play an important role in the biology of the vessel wall.

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