What question did this study set out to answer?

To determine whether combining mutations that confer PAI-1 resistance, slower plasma clearance, and altered glycosylation into rt-PA-TNK improves thrombolytic efficacy compared to wild-type rt-PA.

January 1, 1994Thrombosis and Haemostasis

Comparative Thrombolytic Properties of Tissue-Type Plasminogen Activator and of a Plasminogen Activator Inhibitor-1 -Resistant Glycosylation Variant, in a Combined Arterial and Venous Thrombosis Model in the Dog

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Authors

DCDésiré CollenOklahoma Medical Research Foundation JSJean–Marie StassenBoehringer Ingelheim (Germany)TYTsunehiro YasudaHarvard University

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Implication

Animal experimental study demonstrates enhanced thrombolytic potency and reduced clearance with rt-PA-TNK in canine thrombosis models, suggesting improved efficacy over wild-type rt-PA.

Key Points

To determine whether combining mutations that confer PAI-1 resistance, slower plasma clearance, and altered glycosylation into rt-PA-TNK improves thrombolytic efficacy compared to wild-type rt-PA.
Evaluated 60-minute intravenous infusions of rt-PA or rt-PA-TNK (0.125 to 1.0 mg/kg) in groups of 4 to 5 dogs with combined venous and platelet-rich arterial eversion graft thrombosis receiving heparin and aspirin.
Measured venous clot lysis, clearance rates, arterial recanalization frequency, and total patency time across a 2-hour observation period.
Maximal rate of venous lysis was significantly higher with rt-PA-TNK than rt-PA (480 ± 100% vs 140 ± 40% per mg/kg, p = 0.004) and achieved at a significantly lower dose (0.08 ± 0.01 vs 0.21 ± 0.04 mg/kg, p = 0.004).
Plasma clearance was markedly reduced for rt-PA-TNK compared with rt-PA (240 ± 32 vs 540 ± 49 ml/min, p = 0.002) despite similar specific thrombolytic activity per plasma antigen level.
Arterial recanalization occurred in 10/12 dogs with rt-PA-TNK versus 4/12 with rt-PA (p = 0.07), though cyclic reocclusion occurred with both agents and total patency times over 2 hours did not differ.

Cite This Study

Collen et al. (1994) studied this question.

synapsesocial.com/papers/6a8b103af71b672e3df4645b https://doi.org/10.1055/s-0038-1648819

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Implication

Animal experimental study demonstrates enhanced thrombolytic potency and reduced clearance with rt-PA-TNK in canine thrombosis models, suggesting improved efficacy over wild-type rt-PA.

Comparative Thrombolytic Properties of Tissue-Type Plasminogen Activator and of a Plasminogen Activator Inhibitor-1 -Resistant Glycosylation Variant, in a Combined Arterial and Venous Thrombosis Model in the Dog

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Cite This Study

Comparative Thrombolytic Properties of Tissue-Type Plasminogen Activator and of a Plasminogen Activator Inhibitor-1 -Resistant Glycosylation Variant, in a Combined Arterial and Venous Thrombosis Model in the Dog

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Cite This Study

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