title: Mean transit times and the sites of synthesis and catabolism of tissue plasminogen activator and plasminogen activator inhibitor type 1 in young subjects.
abstract: Using an invasive technique, we studied the mean transit time, the net quantitative turnover rate, and the sites of synthesis and catabolism of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) in healthy young volunteers in the fasting, steady state. Blood was sampled simultaneously from a large hepatic vein, an artery and the inferior caval vein, while measuring the splanchnic plasma flow rate and the plasma volume. We found that the catabolism of active t-PA and t-PA antigen took place in the splanchnic circulation with net rates of 7.2 and 6.3 pmol/min, respectively. The extraction fraction and the mean transit time in the splanchnic circulation were, respectively, 0.63 and 5.6 min for active t-PA and 0.17 and 21 min for t-PA antigen. Active PAI-1 was synthesized in the splanchnic circulation at a rate of 890 IU/min and had a mean transit time of about 9.8 min. No net extraction of PAI-1 antigen took place in the splanchnic circulation. In conclusion, we demonstrated that active t-PA and t-PA antigen are catabolized and active PAI-1 produced in the splanchnic circulation in young healthy subjects during steady state. Furthermore, our data show that active t-PA was also eliminated outside the splanchnic region with a catabolism rate of about 8.4 pmol/min. No net complex formation could be demonstrated in the peripheral circulation. We therefore suggest that active t-PA is eliminated by a re-uptake in the endothelium in the peripheral vessels or in the lung circulation.
authors.affiliation: Thrombosis Centre and Coagulation Laboratory, Gentofte University Hospital, Hellerup, Denmark. majoe@gentoftehosp.kbhamt.dk
authors.forename: M
authors.initials: M
authors.lastname: Jørgensen
authors.forename: K R
authors.initials: KR
authors.lastname: Petersen
authors.forename: N
authors.initials: N
authors.lastname: Vinberg
authors.forename: J
authors.initials: J
authors.lastname: Jespersen
authors.forename: J
authors.initials: J
authors.lastname: Gram
authors.forename: K H
authors.initials: KH
authors.lastname: Tønnesen
mesh_terms: D000328:Adult; D001692:Biological Transport; D001783:Blood Flow Velocity; D001810:Blood Volume; D002404:Catheterization; D006801:Humans; D007700:Kinetics; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D013152:Splanchnic Circulation; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D010959:Tissue Plasminogen Activator