FIBRINOLIZYN (a synonym plasmin) — serinovy protease (KF 3. 4. 21. 7), whether causing splitting - zil-argininovykh and lysyl-lizino-vykh peptide bonds in proteinaceous substrates.
Main function F. consists in a lysis of fibrin (see) and fibrinogen (see). T. also splits V, VIII and XII blood-coagulation factors (see. Coagulant system of blood), a glitch rutting, a growth hormone (see Somapgo-tropiy hormone), ^-globulins ((((((((((see Immunoglobulins), are activated by several proferments of a complement (see). T. has esterazny activity in relation to ethers and amides of the main amino acids.
Medico-biol. fibrinolitic action F matters. on fibrin of blood clots and fibrinogen of a blood plasma. As a result of action F. fibrinogen and fibrin are split on fragments: fibrin of a prevr
shchatsya in the proteins dissolved in a blood plasma with smaller a pier. it is powerful (weight). At the same time high-molecular fragments of X and Y are formed in the beginning, and fragments of X keep ability to be curtailed under the influence of thrombin (see), then late fragments of D and
E. F. in the form of the inactive predecessor — a plazmynogena — is in a blood plasma of the person and animals, a placenta, sperm, myometriums, an endometria. Plasminogen represents a glycoprotein about a pier. it is powerful apprx. 90 Ltd companies — 94 Ltd companies, containing apprx. 2% of carbohydrates. Its primary structure is presented by one poly-peptide chain consisting of 791 amino-acid rests with glutaminic amino acid or a lysine on the N-end.
Activation of a plazmynogen in F. occurs in two ways: vnutren
to them and external. A mediator at activation in the internal way are the active XII blood-coagulation factors participating also in activation of system of a complement and kinin system (see Kinina). Activation happens in the external way under the influence of several fiziol. activators: fabric,
plasma and urokinases (see. Fibrinolitic means). At the same time there is a splitting at least of two peptide bonds in a molecule of a plazmynogen and education F., consisting of two chains connected by disulfide bridges. The heavy chain has a pier. weight apprx. 60 Ltd companies, a light chain about a pier. weight apprx. 25 Ltd companies supports the active catalytic center consisting of the remains of serine (see) and a histidine (see). In a heavy chain F. there are lysineconnecting sites defining affinity of enzyme to fibrin, anti-plasmin, the fabric activator and a nek-eye to amino acids. Pier. the weight of fibrin of a lysine — 76 500 — 85 Ltd companies; at a neutral pH value it is a little stable. In the presence of casein, glycerin and neutral salts its stability sharply increases. At pH 2,0 fibrinolysin is besieged by addition of 1 M of NaCi solution. An optimum pH value for action F. depends on substrate. For proteinaceous substrates an optimum of pH within 7,0 — 8,0, for ethers of arginine 8,0 — 9,0, the lizino-Vyya ethers are split at pH 6,5.
Activity F. determine by degree of hydrolysis by it gelatin, fibrin, casein, ethers of arginine and a lysine, and also by splitting of chromogenic S-2251 substrate. By method of fibrinous plates activity F. determine by a difference of the sizes of zones of a lysis on not heated-up and heated-up (at f 86 ° within 30 min.) plates. Activity F. determine by ability to cause a lysis of a fresh standard fibrinous clot and express it in fibers and and about l it and ches to and x e d in and tsa x lei with t in and I am (PIECE). Activity F. express also in terms of HUNDRED (Committee of Trombolitic Agents) and kazennoliti-chesky units. One kazennoliti-chesky unit corresponds to such amount of fibrinolysin, to-ry releases from 4% of solution of casein in the phosphatic buffer with pH 7,4 at t ° 35 ° within one hour 450 mkg of tyrosine, soluble in trichloroacetic to - those. In a blood plasma of the person it is almost not revealed free F., but at the normal content of plasminogen 4 PIECES of fibrin of a lysine can be formed.
Fibrinolysin as medicine. Medicine of the purified proteolytic enzyme of fibrinolysin is used as thrombolytic means. T. — white hygroscopic powder. Let's dissolve in isotonic solution of sodium chloride. T. receive activation of plasminogen (plasminogen) various activators (trypsin, a strentokinaz, etc.).
T. possesses anesthetic and spasmolytic action. The mechanism of removal or easing of pain can depend both on spasmolytic properties, and on destruction of secondary blood clots and reduction in this regard of ischemia around the site of a necrosis at patients with a myocardial infarction.
At administration of solution of fibrinolysin coagulability of blood therefore it is reasonable to apply F can increase. with heparin, and in the subsequent — with anticoagulants of indirect action (see Anticoagulants).
The main indication to use F. the thromboembolism of a pulmonary artery, vessels of a brain, and also a myocardial infarction, thrombophlebitis, etc. are
F. release in the form of powder in bottles. In order to avoid loss of activity of enzyme contents of a bottle are dissolved just before the use in sterile isotonic solution of sodium chloride in the ratio by 100 — 160 PIECES on 1 ml. Add heparin at the rate of 10 000 PIECES on each 20 000 PIECES of fibrinolysin to solution of fibrinolysin, enter mix into a vein with initial velocity of 10 — 15 drops in min. Daily dose F. makes usually 20 000 — 40 000 PIECES, duration of introduction 3 — 4 hours.
After the end of administration of mix continue to enter heparin on 40 000 — 60 000 PIECES a day intravenously or intramusculary within
2 — 3 days. In the next days the dose of heparin is gradually reduced and appoint anticoagulants of indirect action. For the purpose of creation of high concentration F. in the field of blood clot the method of its introduction directly to a zone of blood clot is developed, in particular at fibrinferment of coronary vessels of heart — vnutrikoro-narno through a catheter. At the same time enter the mix containing 5000 PIECES of fibrinolysin and 2500 PIECES of heparin, dissolved in 50 ml of isotonic solution of sodium chloride. Treatment is carried out under control by koagulo-grams (see). The prothrombin time shall be extended no more than twice in comparison with norm; at the same time the content of fibrinogen shall not be less than 100 mg of %. Accuracy of dosing F. considerably raises after preliminary definition of resistance of an organism to F.
As proteinaceous drug F. has antigenic properties. At its drop introduction there can be nonspecific reactions to protein (the hyperemia of the person, pain on the course of a vein, in to-ruyu enter solution, pains behind a breast and in a stomach, a fever, fervescence, emergence of a small tortoiseshell, etc.). These phenomena can be removed by reduction of rate of administering, at more expressed reaction it is necessary to stop introduction. At the same time antihistamines have favorable effect.
Contraindications to use F. hemorrhagic diathesis, bleedings, a fibrinogenopenia, a pulmonary tuberculosis in an acute form, open wounds, a peptic ulcer, nephrite, a radial illness are. At damages of a brain a relative contraindication to use F. the ABP is high.
Form of release: the bottletight bottles containing
10 000, 20 000, 30 000 and 40 000 PIECES of fibrinolysin complete with the bottles containing 100, 200, 300 or 400 ml of sterile isotonic solution of sodium chloride. Storage: at a temperature from 2 to 10 °.
Bibliography: Urgent problems haemo -
staziologiya, under the editorship of B. V. Petrovsky, etc., M., 1981; Andreenko G. V. Fibrinolysis, Chemistry and physiology of process, M., 1967; it, Fibrinolysis. (Biochemistry, physiology, pathology), M., 1979; Biochemistry of animals and person, iod of an edition M. D. Kursky, century 6, page 84, Kiev, 1982; D A. I. revina and r and N sh t e y E. Ya. Klinik's N, treatment and recovery of working ability of patients with thrombophlebitis, L., 1971; Kudryashov B. A. Biological problems of regulation of liquid state of blood and its coagulation, M., 1975; Methods of a research of fibrinolitic system of blood, under the editorship of G. V. Andreenko, M., 1981; Fib
rinoliz, Modern fundamental and clinical concepts, under the editorship of P. J. Gaffney and S. Balkuv-Ulyutin, lane with English, M., 1982; Chazov E. I. both JI and to and K. M N. Anticoagulants and fibrinolitic means, M., 1977;
H and z about in E. I. and d the ruble Vnutrikoronar-ny administration of fibrinolysin at an acute myocardial infarction, Rubbed. arkh., t. 48, No. 4, page 8, 1976.
G. V. Andreenko; To. M. Lakin (pharm.).