Abstract
Three different dose of 3H-heparin were injected intravenously into rats in order to investigate its anticoagulant activity and to measure radioactivity in blood, urine, bile and organs. Also Dose-II (83.34U/kg) of 3H-heparin was injected intravenously into surgically modified rats to elucidate possible metabolism of 3H-heparin.
The anticoagulant activity of intravenously administered 3H-heparin lasted 90 minutes with Dose-I (41.67U/kg) and 150 minutes with Dose-II and Dose-III (166.68U/kg). The discrepancy was observed between anticoagulant activity and radioactivity in circulating blood, indicating the presence of biologically inactive heparin. About 40% of the total radioactivity was excreted in urine for 5 hours with Dose-II, most of which was excreted within the first hour. The excreted radioactive substance possessed minimum anticoagulant activity. Also this substance was found to be devoid of higher molecular weight portion of 3H-heparin which was proven to have high anticoagulant activity. The radioactivity excreted in bile for 5 hours was less than 1.5% of total injected radioactivity. Among five organs tested, a considerable amount of radioactivity was found in kidneys and liver. Bilateral nephrectomy did not alter the decreasing pattern of radioactivity and anticoagulant activity in circulating blood. However, hepatic devascularization greatly altered the pattern of radioactivity and anticoagulant activity in blood and contributed to prolongation of anticoagulant effect.
It was postulated from this experiment that when 3H-heparin is injected intravenously, its smaller molecular weight portion and excess heparin, if any, are excreted rapidly through kidney and its higher molecular weight portion under-goes depolymerization into smaller molecular weight heparin mainly in liver and then excreted into urine in the form of smaller molecular weight substance.
