Macromolecular ensembles of internal and external fibrinolysis: the resources for enhancement of thrombolysis efficacy.
The results of the search for new plasminogen activators for thrombolytic therapy have been reviewed with analysis of slowdown in this process. The reserves of increasing the effectiveness of thrombolysis are considered and the mechanisms underlying the interactions between plasminogen and its activators with fibrin are described. The domain composition of the fibrinolytic agents and the functional role of their structural elements in fibrinolytic interactions are discussed. The action of fibrin-specific and fibrin-nonspecific plasminogen activators in fibrinolysis has been evaluated. The necessity of the investigation of the regularities of internal and external fibrinolysis has been substantiated. The internal fibrinolysis became the resource for enhancement of thrombolysis efficacy. The approaches to the use of internal fibrinolysis to increase the effectiveness of enzyme therapy (monotherapy with plasminogen or new-made plasminogen activator as well as polytherapy with combination of different plasminogen activators /thrombolysis trigger plus third-generation plasminogen activator of prolonged action/) have been outlined and the relationship between this research and the current tendencies in the improvement of clinical thrombolysis (dose reduction, adjacent therapy, etc.) has been discussed.
Maksimenko
Alexander V
AV
Institute of Experimental Cardiology, Russian Cardiology Research-and-Production Complex, Moscow. alexmak@cardio.ru
Tischenko
Elena G
EG
D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D003328:Coronary Thrombosis / Q000188:drug therapy; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D010960:Plasminogen Activators / Q000627:therapeutic use; D015912:Thrombolytic Therapy
D000933:Antifibrinolytic Agents; D010960:Plasminogen Activators