Background: Preventing and control of bleeding is important in various areas of clinical medicine in the light of increasing number of patients with hemorrhagic manifestations, extensive use of anticoagulants, increasing number of invasive diagnostic, and treatment methods. However, the drugs traditionally used in medical practice to control bleeding are often inefficient and unable to lead to effective reduction in blood loss. One of the ways to find new methods of bleeding prophylaxis is to develop means of pharmacological correction of hemostasis system. The results of the previous research show potentially high activity of some new nitrogen-containing heterocyclic derivatives relating to hemostasis system in vitro and in vivo.
Aims and Objectives: To examine system hemostatic activity of first synthesized benzylammonium salt 2-[3-methyl-1-npropyl-7-(1,1-dioxothietanil-3) xantinyl-8-thio]acetic acid (Compound I) under experimental conditions in vitro and in vivo.
Materials and Methods: Experimental work in vitro is performed on the blood of healthy male donors, under conditions in vivo it is done on intraperitoneal injection of equimolar concentrations of the test substances. Thromboelastography (TEG) was carried out with apparatus TEG 5000. The analysis of the thromboelastograms enabled to define general tendency of coagulation, functional activity of platelets and fibrinogen, fibrinolysis activity, and physicomechanical properties of the formed clots. The influence of firstly synthesized xanthine derivative and ethamsylate on the functional activity of platelets in vitro and in vivo was studied using a laser platelet aggregation analyzer Biola 230LA. The research evaluated the general nature of aggregation, value of maximum aggregation, maximum rate of aggregation, and average size of platelet aggregates. Experimental evaluation of the system specific hemostatic activity in vivo was carried out using the model of parenchymatous bleeding in immature male rats.
Results: The interference came amid registration of bleeding stop time and extent of blood loss. Proagregate effect of Compound I is successfully realized into the system hemostatic activity under conditions of parenchymatous bleeding, exceeding the performance of the control group and the etamsylate group.
Conclusion: The findings reveal potentially high systemic hemostatic activity of Compound I, convincing of the need to further study this compound and its analogues to create on their basis highly efficient, selective correctors of hemostasis system.
Key words: Xanthine Derivatives; Hemostasis System; Proaggragation Activity; Hemostatic Activity
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