Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation.

Yasuda, Tsunehiro; Gold, Herman K.; Leinbach, Robert C.; Yaoita, Hiroyuki; Fallon, John T.; Guerrero, Luis; Napier, Mary E.; Bunting, Stuart; Collen, D.

doi:10.1161/01.cir.83.3.1038

Cited by 91 publications

(39 citation statements)

References 51 publications

(12 reference statements)

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“…This higher concen tration may contribute to the better patency status with YM866 than t-PA after successful thrombolysis. Further improvement of vascular patency may be expected with adjunctive use of antiplatelet agents such as anti GPIIb/IIIa monoclonal antibody (18) and GPIIb/IIIa receptor antagonist (19), or anticoagulants such as throm bin inhibitors (20) and Xa inhibitors (21). A slight but significant decrease (14%) in plasma fibrinogen occurred only with YM866 at 1 mg/kg.…”

Section: Discussionmentioning

confidence: 98%

Experimental Model of Carotid Artery Thrombosis in Rats and the Thrombolytic Activity of YM866, a Novel Modified Tissue-Type Plasminogen Activator

Kawasaki¹,

Kawamura²,

Katoh³

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-We compared the thrombolytic activity of a novel modified t-PA, YM866, with that of t-PA in a rat model of electrically-induced thrombosis. Histological examination revealed the thrombus to be composed mainly of platelet clumps. Measurement of the decrease in carotid blood flow showed that com plete occlusion occurred within 14 min. At 10 min after the induction of thrombus, a test drug (YM866, t PA, or saline) was administered by i.v. bolus injection under heparinization (300 IU/kg, i.v.). Both YM866 and t-PA exhibited dose-dependent thrombolytic activity; the reperfusion rate of YM866 was twice that of t-PA. There was no significant difference in time to reperfusion between the agents, but YM866 showed a greater improvement in patency status after successful thrombolysis than t-PA. Plasma fibrinogen fell slight ly but significantly (14% of baseline value) in animals given 1 mg/kg of YM866. All groups of rats showed a significant decrease in carotid artery blood flow at 1 hr after successful reperfusion or injection of the drug, but this decrease showed significant recovery in animals given 1 mg/kg of YM866. These results suggest that YM866 by single bolus injection is a superior thrombolytic agent to t-PA, and that YM866 can improve the patency status after successful thrombolysis. Furthermore, this platelet-rich thrombosis model permits con tinuous observation of the process of thrombus formation and subsequent thrombolysis and provides a useful tool for the screening and evaluation of efficacy of new antithrombotic agents.

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Section: Discussionmentioning

confidence: 98%

Experimental Model of Carotid Artery Thrombosis in Rats and the Thrombolytic Activity of YM866, a Novel Modified Tissue-Type Plasminogen Activator

Kawasaki¹,

Kawamura²,

Katoh³

et al. 1993

Japanese Journal of Pharmacology

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“…Clinically, a relationship between coronary reocclusion and residual thrombus after thrombolytic therapy has been described (25). Additional doses of a thrombolytic agent (2) or adjunctive therapy with an antiplatelet agent such as anti-GPIIb/IIIa antibody (26) or RGD peptide (27) or with an anticoagulant such as synthetic thrombin inhibitor (28) are considered useful to minimize the resid ual thrombus, as well as to prevent growth of the throm bus.…”

Section: Discussionmentioning

confidence: 99%

Thrombolytic Activity of a Novel Modified Tissue-Type Plasminogen Activator, YM866, in a Canine Model of Coronary Artery Thrombosis

Kawasaki¹,

Katoh²,

Kaku³

et al. 1993

Japanese Journal of Pharmacology

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ABSTRACT-The thrombolytic activity of a novel modified t-PA, YM866, was compared with that of a recombinant t-PA in a canine model of copper coil-induced coronary thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before either drug was administered. YM866 was administered by i.v. bolus injection, while t-PA was given by the same method, as well as by 60-min i.v. infusion. YM866 show ed thrombolytic activity 2 to 4 times as potent as that of t-PA when administered by bolus injection, the difference in thrombolytic effect being obvious in the 3 and 6-hr-old thrombi. Coronary reperfusion was achieved more rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2 mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The residual plasma YM866 and t-PA antigen 30 min after bolus injection was 2570 and 310 of the peak levels, respectively. YM866, administered by i.v. bolus injection, was thus confirmed to exert a thrombolytic effect superior to that of bolus injection and infusion of t-PA, without systemic fibrinolytic activation. These results suggest the potential clinical applicability of YM866 as a thrombolytic agent that can be administered by i.v.bolus injection for acute myocardial infarction.

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“…[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71] Cumulatively, these studies have shown that the dose of fibrinolytic therapy can be substantially reduced to Ϸ50% or even 25% of the dose required in control experiments 57,58 and that fibrinolysis occurs much more rapidly and more completely and is much more stable, as reflected by the absence of cyclic flow variations or reocclusion once flow is restored. Nicolini and associates 65 showed that a low dose of a GP IIb/IIIa inhibitor combined with a low dose of a direct thrombin inhibitor (hirudin) also markedly facilitated coronary fibrinolysis in the canine electrolytic model.…”

Section: Experimental Studiesmentioning

confidence: 99%

Toward a New Frontier in Myocardial Reperfusion Therapy

1998

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Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation.

Cited by 91 publications

References 51 publications

Experimental Model of Carotid Artery Thrombosis in Rats and the Thrombolytic Activity of YM866, a Novel Modified Tissue-Type Plasminogen Activator

Experimental Model of Carotid Artery Thrombosis in Rats and the Thrombolytic Activity of YM866, a Novel Modified Tissue-Type Plasminogen Activator

Thrombolytic Activity of a Novel Modified Tissue-Type Plasminogen Activator, YM866, in a Canine Model of Coronary Artery Thrombosis

Toward a New Frontier in Myocardial Reperfusion Therapy

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