Recombinant Lys-Plasminogen Given Before,But Not After,Recombinant Tissue-Type Plasminogen Activator Markedly Improves Coronary Thrombolysis in Dogs:Relationship of Thrombolytic Efficacy with Parameters of Fibrinolysis
| Autor: | Jawahar L. Mehta, T. G. P. Saldeen, Liying Chen, Wilmer W. Nichols |
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| Rok vydání: | 1996 |
| Předmět: |
Male
medicine.medical_treatment Ischemia Pharmacology Drug Administration Schedule law.invention Plasminogen Activators Dogs law Fibrinolysis medicine Animals Thrombolytic Therapy Chemotherapy biology business.industry Vascular disease Coronary Thrombosis Fissipedia Plasminogen medicine.disease biology.organism_classification Thrombosis Antifibrinolytic Agents Peptide Fragments Tissue Plasminogen Activator Anesthesia Reperfusion Recombinant DNA Female Cardiology and Cardiovascular Medicine business Plasminogen activator |
| Zdroj: | Journal of Cardiovascular Pharmacology. 27:283-289 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-199602000-00016 |
| Popis: | Recombinant tissue-type plasminogen activator (rt-PA) administration rapidly restores blood flow in thrombosed coronary arteries, but coronary arteries often reocclude after initial thrombolysis. This occurs because of the short half-life of rt-PA and rapid increase in plasminogen activator inhibitor (PAI-1) and alpha2-antiplasmin levels in plasma. We hypothesized that administration of lys-plasminogen, which binds to fibrin with 10 times greater affinity and results in a loose fibrin structure (as compared with native glu-plasminogen), before rt-PA would enhance the thrombolytic efficacy of rt-PA and modulate parameters of fibrinolysis. To examine this hypothesis, dogs with electrically induced stable thrombus in the left anterior descending coronary artery (LAD) were treated with saline (group A, n = 9) or lys-plasminogen (group B, 2 mg/kg, n = 5), followed 10 min later by rt-PA (1 mg/kg in 20 min). Four other dogs with occlusive LAD thrombus were first given rt-PA, followed by lys-plasminogen (2 mg/kg) 50 min later (group C). Lys-plasminogen given before rt-PA restored flow in all dogs in 14 +/- 4 min (vs. 22 +/- 9 min in group A, p0.05), continuing2 h (vs. 41 +/- 15 min in group A, p0.02). Lys-plasminogen given after rt-PA did not potentiate the effect of rt-PA. Plasma t-PA antigen concentrations were highest in group B dogs at 2 h after rt-PA infusion. PAI-1 and alpha2-antiplasmin plasma levels were suppressed in all dogs receiving lys-plasminogen whether it was given before or after rt-PA. Therefore, lys-plasminogen given before rt-PA markedly potentiates the effect of rt-PA and alters the parameters of fibrinolysis. In contrast, lys-plasminogen given after rt-PA does not influence the thrombolytic effect of rt-PA, whereas it suppresses PAI-1 and alpha2-antiplasmin levels in plasma. This study also suggests that binding of plasminogen to the clot is more important than the plasma levels of PAI-1 and alpha2-antiplasmin. |
| Databáze: | OpenAIRE |
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