Сравнительный анализ двух методов повышения антикоагулянтной активности гепарина

Abstract

Comparative analysis of blood plasma coagulation with the participation of terbium ions (Tb3+) and complexes of high-molecular-weight heparin with endogenous ligands (adenosine triphosphate, arginine, glycine, and proline) has been performed using published data on the computer simulations of chemical equilibria, results of biochemical experiments in vivo with the blood plasma of laboratory rats, and the modern enzymatic theory of blood clotting. The participation of terbium ions was investigated by the computer simulation of chemical equilibria based on pH-metric data for calcium chloride - terbium nitrate - unfractionated heparin system in physiological solution and by biochemical experiments in vivo with intraperitoneal injections of terbium heparinate and terbium chloride into laboratory rats. It is established that the terbium heparinate at a concentration equivalent to 50 IU heparin and terbium chloride in a concentration of 1.5 × 10-5 - 1.5 × 10-2 M act as coagulants. The hypothetical mechanism of competitive complexation of Tb3+ and Ca2+ ions with blood clotting factors is not confirmed by the results of biochemical experiments that are consistent with the modern enzymatic theory of blood clotting and the blood plasma component composition. Heparin complexes with blood plasma ligands were constructed by the computer simulation of chemical equilibria based on pH-metric data for heparin-L и MCl2-heparin-L (M = Ca2+, Mg2+; L = ATP, Arg, Gly, Pro) systems in physiological solution and by biochemical experiments in vitro and in vivo with blood plasma of laboratory rats. Complexes of heparin with adenosinetriphosphate, arginine, glycine, and proline are non-toxiс, contain organic cations of ligands bound with heparin sulfoanions in their structures, and do not violate the enzymatic blood coagulation process. These complexes regulate the blood coagulation process by decreasing the equilibrium concentration of Ca2+ ions (through the formation of stable complexes) and produce a two- to three-fold increase in the activity of heparin.