Thromboresistance mechanism

Methods for preparing heparin-containing polymeric materials by means of ionic and covalent immobilization of heparin on various polymers are surveyed. The data on the biological activity of heparin are discussed as well as the probable mechanisms of thromboresistance enhancement endowed to polymeric materials by this anticoagulant. Some approaches toward an increased efficiency of anticoagulant properties of immobilized heparin are analyzed, and the position of heparin-containing polymers among other biomedical polymers is discussed. 

Of these the last one has been most widely used, since heparin-modified polymeric materials exhibit the highest and by today unsurpassed effects of thromboresistance enhancement. Many of these materials have not only proved to be potent in trials on animals, but have already found clinical application. These achievements have stimulated continuous interest in heparin-containing polymers (HCP) which is best manifested by listing the investigations performed in the field in recent years and still under way. They involve the new procedures for the synthesis of HCP providing minimal loss of activity of bound heparin, the studies of interactions of HCP with blood and its individual components, as well as on the mechanism of enhanced thromboresistance of HCP, and the search for new tasks for HCP. 

The year of 1961, when Vincent Gott11 observed the inhibition of thrombus formation by immobilized heparin for the first time, was marked as the second birth date of heparin, since it was for the first time isolated from liver tissue. Its anticoagulant action was detected in 1892. Although more than 20 years have passed since Gott s publication, there is still much confusion concerning the views on the mechanism of enhanced thromboresistance of heparin-modified polymers, which greatly hinders the introduction of HCP into clinical practice. 

The prospects for this method as well as for the method involving the generation of free macroradicals by y-irradiation of heparin 95), are provided for by the variety of polymerizable monomers, which makes it possible to produce materials with various physico-mechanical and chemical properties. The in vitro thromboresistance of the copolymers obtained in this way was proportional to the heparin content (Table 9). 

The fact that thromboresistance of HCP is dependent on the method of immobilization of heparin, together with a rather low activity of covalently immobilized heparin, makes the idea of long-term enhancement of thromboresistance of polymers on their heparinization doubtful 54,70,71J. Naturally, the answer can be given only after a detailed analysis of the interaction of HCP with blood and its components and clarification of the mechanism of the effect of the immobilized heparin on the blood clotting system and relying on the results of in vivo tests of these materials are necessary. 

Mechanism of Enhanced Thromboresistance of Polymeric Materials in the Presence of Heparin... 

The results discussed in the previous Section permits to make some assumptions regarding the mechanism of enhanced thromboresistance of HCP. Two self-excluding viewpoints concerning the problem coexist in the literature. The first one implies the elution of heparin from a polymeric surface into the bloodstream which prevents clotting in a way common for the anticoagulant itself64,67 73). According to the second, the... 

To clarify the mechanism of enhanced thromboresistance of such polymers, the state of the blood clotting system before and after the contact with the polymer was examined I36) (Table 19). Obviously, the changes of the blood clotting system parameters are of the same type as those accompanying the interaction of blood with HCP (see Table 16) but essentially exceeding the latter. Consequently, the heparin-protease-... 

Metals such as titanium, stainless steel, nitinol, cobalt-chrome alloys, etc., are used in many devices. Generally, these are metals with passive surfaces or surfaces that can be passivated. Silver has been used as a coating designed to resist infection. Glassy carbons have also been used as coatings to render surfaces thromboresistant. Pyrolytic carbon structures or coatings on graphite have been utilized in the fabrication of bileaflet heart valves. These are the most popular mechanical valves in use today. 

Methyl methacrylate (mMA) was graft pol3nnerized onto dextran in the presence of Ce " " salts. The resulting polymer is neither soluble in water, an excellent solvent for dextran, nor in acetone, an excellent solvent for poly-(methyl methacrylate) (PMMA). A hot-pressed film of the copol3mier not only showed better wettability and water absorbing power than PMMA but also thromboresistance. There was also correlation like matrix mechanism between the molecular weight of the reactant dextran and that of the branch PMMA in the product. 

An ideal synthetic vascular graft should possess several features biocompatibility mechanical strength, and compliance for long-term devices thromboresistance availability in various sizes satisfactory graft healing and ability to withstand infection. 

Its great cellular biocompatibility with the blood and the soft tissue as well as its excellent thromboresistance, does carbon material to be used fundamentally in applications of the circulatory apparatus, blood vessel and mechanical cardiac-valve prosthetic devices, being this last the most extended application. Nowadays, most of the modem heart valves are made with a coating of LTI on a polycrystalline graphite substrate or like a monolithic material [42]. 

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