Seminars in Thrombosis, Thrombolysis and Vascular Biology

Rc, Becker

doi:10.1159/000174879

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…Cardiovascular diseases remain the major cause of mortality and morbidity in the developed world. Thrombolytic therapy, with tissue plasminogen activator (tPA) or streptokinase (SK), to restore blood flow to the coronary arteries, has revolutionized the treatment of acute myocardial infarction (AMI) and improved patient survival (1)(2)(3). Antithrombotic agents, inhibiting platelet aggregation or the activity or generation of thrombin, have been intensively investigated during the last decade, as adjuncts to thrombolytic therapy to accelerate the time to lysis and prevent reocclusion (4)(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Effective Use of BCH-2763, a New Potent Injectable Direct Thrombin Inhibitor, in Combination with Tissue Plasminogen Activator (tPA) in a Rat Arterial Thrombolysis Model

Deschênes¹,

Finkle

Winocour

1998

Thromb Haemost

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SummaryCurrent therapeutic use of heparin as an adjunct to thrombolytic therapy for myocardial infarction is suboptimal with respect to efficacy and bleeding risk. In a rat carotid arterial thrombolysis model (FeCl3-induced injury) we evaluated the combined effect of tPA (2.0 mg/kg/ 30 min) with our potent injectable direct thrombin inhibitor, BCH-2763 (Ki 0.11 nM; MW 1.5 kDa), which, unlike heparin, inhibits bound and free thrombin; comparisons were with standard heparin (SH), other direct thrombin inhibitors, r-hirudin (MW 6.5 kDa) and hirulog (MW 2.3 kDa), or tPA alone. Time to lysis (TL), patency time (PT), aPTT (fold increase) and bleeding time (BT) were determined. ED100 (100% of rats reperfused) for BCH-2763, hirulog or r-hirudin was 1, 3 or 2 mg/kg/60 min, respectively; 67% of rats reperfused with SH at the highest dose tested (220 U/kg/60 min) and 43% with tPA alone. At these doses, TL (min) was shorter (p <0.01) with BCH-2763 (0.5 ± 0.1), hirulog (3.3 ± 2.3) or r-hirudin (2.3 ± 1.0) than SH (66.3 ± 30.8) or tPA alone (93.4 ± 21.4). The aPTT fold increase after 15 min infusion was markedly greater (p <0.001) for SH (32.0 ± 0.8) than BCH-2763 (3.7 ± 0.5), hirulog (5.2 ± 0.3) or r-hirudin (4.5 ± 0.8) in combination with tPA or tPA alone (1.1 ± 0.1). In addition, the BT (min) for BCH-2763 (3.0 ± 0.4) was similar to tPA alone (1.6 ± 0.3), but prolonged (p <0.05) for hirulog (7.5 ± 2.7), r-hirudin (6.6 ± 0.8) or SH (7.3 ± 1.8). Comparisons at same aPTT fold increase revealed that in combination with tPA, BCH-2763 required a lower anticoagulant level to shorten the TL and prolong the PT than hirulog, r-hirudin or SH. Thus, in this rat arterial thrombolysis model direct thrombin inhibitors are more effective than SH as antithrombotic adjuncts to tPA. BCH-2763 is effective at a lower gravimetric dose and more modest aPTT fold increase than hirulog or r-hirudin with less alteration in haemostasis, which may confer an improved safety index.

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Section: Introductionmentioning

confidence: 99%

Effective Use of BCH-2763, a New Potent Injectable Direct Thrombin Inhibitor, in Combination with Tissue Plasminogen Activator (tPA) in a Rat Arterial Thrombolysis Model

Deschênes¹,

Finkle

Winocour

1998

Thromb Haemost

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Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects

et al. 1998

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The freeze-dried powder of Lumbricus rubellus earthworm was administered orally to rats and its fibrinolytic and antithrombotic effects were investigated. The fibrinolytic activity of plasma was determined by measuring the plasmin activity of the euglobulin fraction and was increased to two-folds of the control at a dose of 0.5 g/kg/day and five times with 1 g/kg/day after 4-day administration. The antithrombotic effect was studied in an arterio-venous shunt model of rats. The thrombus weight decreased significantly from 43.2 mg to 32.4 mg at a dose of 0.5 g/kg/day after 8-day treatment. The level of fibrinogen/fibrin degradation product (FDP) in serum was elevated in a dose-dependent manner during the treatment period. On the 8th day after administration, the FDP value was increased to 7.7 micrograms/ml compared with the control value of 3.3 micrograms/ml. These results support that earthworm powder is valuable for the prevention and/or treatment of thrombotic conditions.

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Antithrombotic effects by oral administration of novel proteinase fraction from earthworm eisenia andrei on venous thrombosis model in rats

et al. 2007

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A novel proteinase fraction, SPP-501, was purified from the earthworm, Eisenia andrei, and its antithrombotic effects compared with those of urokinase and t-PA (tissue type-plasminogen activator) in a thrombosis model, induced by the insertion of a stainless wire coil into the inferior vena cava. SPP-501, urokinase and t-PA were administrated once a day for 14 days. On the oral administration of SPP-501, as well as urokinase and t-PA, the thrombus weight was dramatically decreased. The euglobulin lysis time (ELT) was also shortened by SPP-501, but urokinase and t-PA failed to dissolve the euglobulin clot. Conversely, urokinase and t-PA produced detectable fibrinogen/fibrin degradation products (FDP), but SPP-501 did not. Thrombin induced platelet aggregation was desensitized in the SPP-501 treatment groups. With a high dose of SPP-501 (45 mg/kg), the APTT (activated partial thromboplastin time) was prolonged. These results suggest that SPP-501 shows both antithrombotic and fibrinolytic activities when orally administered.

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Seminars in Thrombosis, Thrombolysis and Vascular Biology

Cited by 4 publications

References 17 publications

Effective Use of BCH-2763, a New Potent Injectable Direct Thrombin Inhibitor, in Combination with Tissue Plasminogen Activator (tPA) in a Rat Arterial Thrombolysis Model

Effective Use of BCH-2763, a New Potent Injectable Direct Thrombin Inhibitor, in Combination with Tissue Plasminogen Activator (tPA) in a Rat Arterial Thrombolysis Model

Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects

Antithrombotic effects by oral administration of novel proteinase fraction from earthworm eisenia andrei on venous thrombosis model in rats

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