New thrombolytic strategy: bolus administration of tPA and urokinase-fibrinogen conjugate.
Increased efficacy of thrombolytic therapy requires a comprehensive search for new and novel therapeutic strategies. Many new modified forms of plasminogen activators have been obtained by means of chemical and biological synthesis. However, clinical findings demonstrate that the reperfusion level achieved during thrombolysis remains the same for various thrombolytic agents, irrespective of an extensive search for an "ideal" thrombolytic. Thrombolytic therapy may be complicated by treatment delays, cumbersome schemes of preparation and administration, and hemorrhagic and rethrombotic events. These limitations may be overcome, at least in part, by applying combined thrombolysis with plasminogen activators exhibiting complementary actions and different pharmacokinetic profiles. The combined action of native thrombolytics allows the use of lower doses and simplified schemes of administration, yielding encouraging results in experimental models. Long-acting forms of plasminogen activators are being developed and tested in combination with tissue-type plasminogen activator as a trigger of thrombolysis. The combination of short- and long-acting plasminogen activators appears promising and potentially eligible for bolus administration to patients. On the basis of our own experimental results and data in the literature, we suggest a new thrombolytic strategy connected with the single injection of a combination of complementary and pharmacokinetically different plasminogen activators.
Maksimenko
A V
AV
Laboratory of Biochemical Engineering, Department of Biotechnology, Institute of Experimental Cardiology, Russian Cardiology Research Center, Moscow, Russia.
Tischenko
E G
EG
D000818:Animals; D004285:Dogs; D004338:Drug Combinations; D005340:Fibrinogen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D012008:Recurrence; D015912:Thrombolytic Therapy / Q000009:adverse effects; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D004338:Drug Combinations; D005343:Fibrinolytic Agents; D005340:Fibrinogen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator