January 1, 1992Thrombosis and Haemostasis
The Effect of Thrombin Inhibitors on Tissue Plasminogen Activator Induced Thrombolysis in a Rat Model
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Discussion
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Implication
Randomized animal study reveals direct thrombin inhibitors improve arterial patency after t-PA thrombolysis in rats, indicating clot-bound thrombin inhibition aids reperfusion.
Key Points
- To evaluate whether antithrombin III-independent thrombin inhibitors outperform heparin in accelerating t-PA-induced clot dissolution and preventing arterial reocclusion.
- Distal aortic red cell- and fibrin-rich thrombi were generated in rats using balloon catheter endothelial denudation paired with external constriction.
- Thrombolysis was initiated via t-PA (1 mg/kg bolus, then 1 mg/kg/h over 30 min), followed by randomized 80-minute infusions of saline, heparin, hirudin, hirulog, or PPACK adjusted to prolong baseline APTT 4-fold.
- Aortic blood flow and trans-stenotic blood pressures were continuously monitored to calculate time to clot lysis and arterial reocclusion frequency.
- Hirudin, hirulog, and PPACK significantly increased arterial patency time from 63.9 ± 7.7% with saline to 90.7 ± 2.2%, 94.0 ± 0.9%, and 94.7 ± 1.0%, respectively (p < 0.01), by reducing reocclusions, whereas heparin showed no significant effect.
- Low-molecular-weight inhibitors hirulog and PPACK significantly shortened time to thrombolysis from 10.5 ± 2.3 min (saline) to 4.4 ± 0.6 min and 4.2 ± 0.8 min, respectively (p < 0.02), whereas heparin and hirudin did not.
Cite This Study
Klement et al. (1992) studied this question.