• Modeling Mechanism：

  Argatroban Monohydrate, as a direct thrombin inhibitor, inhibits thrombin-mediated fibrinogenesis, platelet aggregation, and coagulation factor activation by reversibly binding to the thrombin active site. It can also penetrate the thrombus to inhibit thrombin-binding thrombin activity, preventing thrombus reformation. When synergistically used with t-PA, it reduces intermittent reocclusion during t-PA thrombolysis, accelerates thrombus dissolution, and does not interfere with the fibrinolytic system.

• Related Products：

  Argatroban Monohydrate (T22246)

• Modeling Method：

  Experimental Subject：

  Hamsters: Golden hamsters, male, body weight 120–130 g

  Dosage and Administration Route：

  ① Thrombosis induction:
  - Anaesthesia: Sodium pentobarbital (100 mg/kg) administered intraperitoneally for induction, tracheotomy performed for ventilation maintenance. Right subclavian artery cannulated (PE10 catheter) to the common carotid artery opening; right femoral vein cannulated for drug administration;
  - Thrombosis induction: Sodium fluorescein (50 mg/kg) injected into the right subclavian artery. Five minutes later, a small vein (diameter 50–70 μm) was selected and locally irradiated with filtered light (diameter 100 μm, intensity 20 mW/mm², wavelength 400–500 nm) until thrombosis caused 99% luminal stenosis(approximately 7 minutes);
  ② Thrombolytic intervention:
  - Fifteen minutes after thrombus formation, initiate continuous infusion of t-PA (72×10⁴ IU/kg/h) into the right subclavian artery, concurrently with continuous infusion of Argatroban (0.05–0.3 mg/kg/h) via the femoral vein for 4 hours;
  - Control treatment:
  - Blank control: Normal saline infusion via femoral vein;
  - UFH control: UFH (12.5 anti-Xa U/kg/h) administered via femoral vein infusion, with all other aspects identical to the intervention group.

  Dosing Frequency and Duration Model：

  Single dose

• Validation：

  1. Thrombolysis indicators: - Vascular stenosis rate: One hour after thrombolysis, the vascular stenosis rate in the argatroban (0.1 mg/kg/h) group decreased to 59.6±4.0% (93.2±2.5% in the control group, p<0.01), and further decreased after 4 hours, showing a dose-dependent effect; - Thrombus area percentage: One hour after thrombolysis, the thrombus area percentage in the argatroban (0.3 mg/kg/h) group was only 37.9±16.9% (79.4±9.5% in the UFH group, p<0.01); 2. Coagulation function indicators: - Activated partial thromboplastin time (aPTT): The aPTT in the argatroban (0.3 mg/kg/h) group was prolonged to 34.6±2.1 s (28.8±0.4 s in the control group, p<0.01), without excessive prolongation (<180 s); Bleeding time (BT): The BT was not significantly prolonged in the argatroban (0.1-0.2 mg/kg/h) group (216-228 s vs. 204±6 s in the control group), while the BT was prolonged to 265±9 s in the 0.3 mg/kg/h group (p<0.01), but no serious bleeding complications occurred; 3. Re-occlusion: The incidence of intermittent re-occlusion within 1 hour of thrombolysis in the argatroban group was significantly lower than that in the t-PA alone group and the UFH group.

*Precautions：

*References：Yamada K,et,al. Effects of argatroban and heparin on thrombus formation and tissue plasminogen activator-induced thrombolysis in a microvascular thrombosis model. Thromb Res. 2003 Jan 1;109(1):55-64.