The present study was conducted in order to gain more insight into the disposition and metabolism of heparin after intravenous injection in humans. The major pharmacologic effects of heparin, i.e., anticoagulant and clearing action, are well established, and although almost nothing is known concerning its metabolism, advantage may be taken of its clinical properties. Nonetheless, an understanding of the metabolism and, ultimately, the exact mechanism of the action of heparin may show the way for additional applications or possible limitations of this substance.Since heparin is a comparatively complex molecule which can interact with various body constituents, the problem of its chemical determination is extremely difficult and in many cases unreliable. This problem is further complicated by the fact that a number of substances (chondroitin sulfate, mucins and hyaluronic acid) chemically related to heparin are also present in all parts of the body, and complete separation of minute amounts of heparin from these materials cannot always be accomplished. In order to make quantitative studies on the metabolic disposition of heparin, it was necessary to employ radioactive heparin prepared in our laboratory as previously described.' Before injecting our radioactive heparin into human beings, extensive studies were conducted on the intravenous administration of this material into dogs. A number of the findings from study of these animals have been reported.2-6 Since the radioactive heparin produced no disturbing toxic effects and most of it was found to be excreted in a rather short period, subsequent studies were carried out in humans. The present report describes our findings in some of these experiments, i.e., the clearance of radioactive heparin from the blood, and the excretion from the urine. In addition, some results on the identification of the urinary radioactive components are presented.
METHODSHeparin-535, having a specific activity of 13,350 cpm per mg, was prepared in our laboratory according to the procedure described in a previous publication. It was dissolved in physiologic saline to give a concentration of 10 mg per ml, and the solution was sterilized by passage through a bacterial filter.Clotting time was determined according to the Lee and White method.7 Radioactivity in blood was assayed on 10-ml samples of whole blood. These samples were combusted, precipitated as barium sulfate and assayed as such. Urinary radioactivity was measured on planchets which were plated with urine and dried. The radioactivity was measured on a thin window gas flow counter. Sufficient counts were taken to reduce the counting error to no more than 5 per cent. EXPERIMENTS 1. The patient was injected intravenously with 5 mg of radioactive heparin in 0.5 ml of saline. There were no ensuing toxic reactions, and the clotting time did not change appreciably. The urine was collected for 2 days, each 24-hour sample being kept separately. One radioactivity assay was made on the original urines and another after inorganic sulfate w...
