Dependence of fibrinolytic activity on the concentration of free rather than total tissue-type plasminogen activator in plasma after pharmacologic administration
Abstract
To identify factors responsible for the decline of plasma tissue-type plasminogen activator (t-PA)-specific activity that we have observed after infusions of the activator and to define the potential usefulness of selected variants of t-PA in obviating them in patients with infarction, serial plasma samples from patients (n = 4) and rabbits (n = 15) given t-PA were assayed for total t-PA antigen, t-PA activity, and free as opposed to type-1 plasminogen activator inhibitor (PAI-1)--complexed t-PA. In patients, attenuation of t-PA specific activity after infusions was evident with concentrations of total t-PA antigen that were as much as sevenfold greater than pretreatment values (62 compared with 9 ng/ml). Attenuation of t-PA activity corresponded with the disappearance of free t-PA from plasma and was associated with persistence of complexes of t-PA with PAI-1. In normal rabbits (n = 4) given wild-type t-PA by bolus injection, PAI-1 activity was 4 +/- 1 arbitrary units/ml. Attenuation of t-PA activity was not evident until 60 minutes after injection at a time when total plasma t-PA antigen concentration was as low as 13 +/- 8 ng/ml. Under these conditions, plasma t-PA was composed predominantly of free t-PA. In rabbits (n = 5) ...Continue Reading
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