Kinetics Of Anticoagulant And Lipolytic Activity And Radiolabel After Intravenous Administration Of ³⁵S-Heparin Fractions Of Different Molecular Weight

Heparin fractions were prepared from commercial pig mucosal by affinity chromatography on antithrombin III, ³⁵S- radiolabelling and gelchromatography. Three fractions were obtained with moLwt.of < 6.000, 6 - 35.000 and > 35.000 daltons. They were administered intravenous as a bolus into human volunteers. The anticoagulant activity was measured with the APTT and Xa inactivation, using standard curves. The lipolytic activity was as^ed as hepatic triglyceride lipase activity, and as extra-hepatic lipoprotein lipase activity by hydrolysis of tritiated triolein. Radioactivity data were corrected for degraded heparin fragments uncomplexed to protein by subtracting radiolabel with a mol.wt. < 10.000 passing through a filter.

Low mol.wt. fractions induced neither of both lipase activity and had no effect on the APTT. Anti Xa activity and radioactivity disappeared in parallel with slightly concave curves in semilogarthmic plots. Heparin of intermediate and high mol.wt. induced both lipolytic and both anticoagulant activities. The elimination of radioactivity, hepatic triglyceride lipase activity and anti-Xa activity occurred parallel according to a convex curve in semilogarthmic plots. The extra-hepatic lipoprotein lipase activity disappeared following a slightly concave curve.

These data indicate that relatively large heparin molecules are required for lipolytic and APTT activity. Hepatic triglyceride lipase activity might be present complexed to heparin, comparable to the antithrombin III-heparin complex. The elimination of anti Xa activity and hepatic triglyceride lipase activity might be determined by the heparin part of the complexes.