Endothelial Binding of Recombinant Tissue Plasminogen Activator: Quantification In Vivo Using a Recirculatory Model

SummaryThe catabolism of recombinant tissue plasminogen activator (rt-PA) was investigated after injection of radiolabelled material into rats. Both Iodogen and Chloramine T iodination procedures yielded similar biological activity loss in the resultant labelled rt-PA and had half lives in the rat circulation of 1 and 3 min respectively. Complex formation of rt-PA was investigated by HPLC gel exclusion (TSK G3000 SW) fractionation of rat plasma samples taken 1-2 min after 125I-rt-PA injection. A series of radiolabelled complexes of varying molecular weights were found. However, 60% of the counts were associated with a single large molecular weight complex (350–500 kDa) which was undetectable by immunologically based assays (ELISA and BIA) and showed only low activity with a functional promoter-type t-PA assay. Two major activity peaks in the HPLC fractions were associated with Tree t-PA and a complex having a molecular weight of ̴ 180 kDa. HPLC fractionation to produce these three peaks at various timed intervals after injection of 125I-rt-PA showed each to have a similar initial rate half life in the rat circulation of 4-5 min. The function of these complexes as yet is unclear but since a high proportion of rt-PA is associated with a high molecular weight complex with a short half life in the rat, we suggest that the formation of this complex may be a mechanism by which t-PA activity is initially regulated and finally cleared from the rat circulation.

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Double Treatment of Severe Hepatic Veno-occlusive Disease after Allogeneic Peripheral Blood Progenitor Cell Transplantation with Recombinant Tissue Plasminogen Activator

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657735 ◽

1997 ◽

Vol 78 (04) ◽

pp. 1299-1300

Author(s):

Dietmar Söhngen ◽

Ulli Bauser ◽

Christiane Boogen ◽

Carlo Aul ◽

Thomas Frieling ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Cell Transplantation ◽

Peripheral Blood ◽

Progenitor Cell ◽

Recombinant Tissue Plasminogen Activator ◽

Occlusive Disease ◽

Peripheral Blood Progenitor Cell ◽

Tissue Plasminogen

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Bioavailability in Rats of Human Recombinant Tissue Plasminogen Activator After Subcutaneous and Intramuscular Injection

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661671 ◽

1986 ◽

Vol 56 (03) ◽

pp. 299-301 ◽

Cited By ~ 5

Author(s):

L J Garcia Frade ◽

S Poole ◽

S Hanley ◽

L J Creighton ◽

A D Curtis ◽

...

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Fibrinolytic Activity ◽

Inferior Vena ◽

Peak Plasma ◽

Plasma Concentrations ◽

Vena Cava ◽

Recombinant Tissue Plasminogen Activator ◽

Fibrin Plate ◽

Tissue Plasminogen

SummaryThe bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

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