Abstract
Aim:
To evaluate the effects of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism (APT) in animal models.
Methods:
Both rabbit and dog APT models were used. For the rabbit APT model, the thrombi weight before and after administration was measured. Central venous pressure (CVP) and mean arterial pressure (MAP) were measured before and 15, 30, 60, and 120 min after the injection of the blood clot. Partial thromboplastin time (APTT), prothrombin time (PT), platelet count, and fibrinogen concentration were measured using auto analyzers. Plasminogen activity was measured based on chromogenic substrates. In the dog APT model, pulmonary blood flow was recorded using pulmonary angiography.
Results:
Intravenous administration of FIIa (0.1–5.0 mg/kg) improved the APT-induced hemodynamic derangements and reduced thrombi weight. The angiography evidence also showed that the pulmonary emboli had almost disappeared after FIIa infusion. FIIa (0.1, 0.5, or 1.0 mg/kg) did not impair the coagulation pathways, although very high doses of FIIa (5.0 mg/kg) could stimulate the production of plasminogen and result in impairment of the pathways.
Conclusion:
FIIa could effectively protect against APT via degradation of thrombi with less activation of plasminogen, and may provide a novel fibrinolytic enzyme for targeting the main pathological processes of the disease.
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Acknowledgements
Project was supported by the National Natural Science Foundation of China (No 81000209), the key Project of Chinese Ministry of Education (No 210255), and the Fundamental Research for the Central Universities (No 21609304).
The authors thank Dr Jun XIE and the staff at the Molecular Imaging Lab in the Department of Radiology at the 3rd Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, for their technical assistance.
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Lin, X., Liang, Xx., Tang, Jj. et al. The effect of the fibrinolytic enzyme FIIa from Agkistrodon acutus venom on acute pulmonary thromboembolism. Acta Pharmacol Sin 32, 239–244 (2011). https://doi.org/10.1038/aps.2010.193
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DOI: https://doi.org/10.1038/aps.2010.193
