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Journal Technologies of Living Systems №3 for 2009 г.
Article in number:
HEMORHEOLOGICAL EFFECT OF DESMOPRESSIN AS OF POSSIBLE MECHANISM ITS HAEMOSTATIC ACTIONS
Keywords: erythrocyte aggregation desmopressin rheological properties blood glycosamineglycane
Authors:
N.P. Zdumaeva, V.N. Levin
Abstract:
Despite almost 30-year experience gained in the use of desmopressin (1-deamino-8-D-arginine vasopressin), a synthetic analog of vasopressin, in the treatment of blood clotting disorders, the exact mechanisms of its hemostatic effect remain not quite clear. Primary hemostasis takes place in flowing blood, where the conditions of the flow largely regulate the interactions of blood cells between each other and with the vascular wall. In turn, an important factor, determining the hemodynamic parameters, particularly in microcirculation, is aggregation of the largest blood cell population, erythrocytes. Though the relationship between erythrocyte aggregation and pathological clotting is acknowledged, its modulating effect on physiological hemostatic processes is often neglected. We studied effect of desmopressin on erythrocyte aggregation in experiment in vivo and in vitro. MATERIALS AND METHODS. Experiment was carried out on 19 male albino rats (290-320 g) receiving subcutaneously 0.02 μg /100g body weight of desmopressin (adiuretin; Ferring-Leciva). After 4 h, the animals were narcotized with sodium ethaminal, decapitated, and the blood was collected. Control group consisted of 15 rats. Erythrocyte aggregation index (AI) was determined using a MA1 semiautomated aggregometer (Myrenne); the method is based on the analysis of light beam passing through the blood or cell suspension in a plasma-substituting solution. The blood sample was rotated at a shear rate of 600 sec-1 and after stop the AI was measured automatically for a 10-sec interval. After high-shift rotation the AI was measured at low shear rate (3 sec - 1) for the same time interval. Hematological parameters (hematocrit, hemoglobin concentration, erythrocyte count) were evaluated by universal methods. Fibrinogen concentration was measured by gravimetry. Serum content of acid glycosaminoglycans (GAG) was measured by carbazole color reaction. Plasma and blood viscosities at shear stress of 3.90 and 0.39 N/m2 were measured on a capillary viscosimeter. For studying effect of hormone on erythrocyte aggregation in experiment in vitro blood cells incubated with desmopressin (300 pg/ml). The results were statistically processed using parametric tests. RESULTS. Injection of desmopressin led to pronounced changes in erythrocyte aggregation characteristics. A significant (p<0.001) increase in AI in comparison with the control. It was noticed that desmopressin injections raise blood viscosity (p< 0.001), plasma viscosity (p< 0,001). Close correlation connection of an index of erythrocyte aggregation and viscosity of blood with the contents in plasma acid GAG is revealed. The results evidence for significant action of desmopressin on liquid homeostasis not only by antidiuretic effects on the kidneys, by changing of condition of connecting tissue of the matrix as shown by a marked rise of acid GAG in plasma but also by influence on rheological properties of blood which is an important element of management of transcapillary exchange in tissue microregions. Possible mechanism of hemorheological alterations with desmopressin participation is discussed.
Pages: 65-70
References
  1. Hathcock J.J.Flow effects on coagulation and thrombosis // Arteriosclerosis, Thrombosis, and Vascular Biology. 2006. V. 26. Р. 1729 - 1741.
  2. Eugster M., Reinhart W.H. The influence of hematocrit on primary hemostasis in vitro // Thromb. Haemost. 2005. V. 94 (6). Р. 1213-1218.
  3. Pearson M.J., Lipowsky H.H. Influence of erythrocyte aggregation on leukocyte margination in postcapillary venules of rat mesentery //Am. J. Physiol. Heart. Circ. Physiol. 2000.V. 279. P. H1460-H1471.
  4. Lipowsky H.H.Microvascular rheology and hemodynamics // Microcirculation. 2005. V. 12. P. 5 - 15.
  5. Практическая трансфузиология / под ред. Г.И. Козинца. М.: Изд-во Триада-Х. 1997.
  6. Turitto V.T., Hall C.L. Mechanical factors affecting hemostasis and thrombosis // Thrombosis Research. 1998. V. 92 (6). P. 25 - 31.
  7. Schmid-Schonbein H., Mallota H., Striesow F. Erythrocyte aggregation: causes consequences and methods of assessment // Tijdschr NVKC. 1990. V. 15. P. 88-97.
  8. А.с. № 1352367. Способ определения гликозаминогликанов в сыворотке крови / А.Б. Зборовский, П.И. Исаев.
  9. Kanwar S., Woodman R.C., Poon M.C., Murohara T., Lefer A.M., Davenpeck K.L., Kubes P.Desmopressin induces endothelial P-Selectin expression and leukocyte rolling in postcapillary venules // Blood. 1995. V. 86 (7). P. 2760 - 2766.
  10. Balduini C. L., Noris P., Belletti S., Spedini P., Gamba G. In vitroand in vivo effects of desmopressin on platelet function // Haematologica. 1999. V. 84. P. 891 - 896.
  11. Григорьев А.И., Ларина И.М., Буравкова Л.Б., Гончарова А.Г., Доброхотов И.В., Наточин Ю.В. Сравнение антидиуретической реакции почек человека при различных способах введения препарата вазопрессина // Физиология человека. 2003. Т. 29 (3). C. 89 - 97.
  12. Mannucci P.M. Desmopressin (DDAVP) in the Treatment of Bleeding Disorders: the First Twenty Years // Blood. 1997. V. 90. P. 2515 - 2521.
  13. Windberger U., Bartholovitsch A., Plasenzotti R., Korak K. J., HeinzeG.Whole blood viscosity, plasma viscosity and erythrocyte aggregation in nine mammalian species: reference values and comparison of data // Exp Physiol. 2003. V. 88. P. 431 - 440.
  14. Baskurt O. K., Farley R. A., Meiselman H. J.Erythrocyte aggregation tendency and cellular properties in horse, human, and rat: a comparative study // Am. J. Physiol. Heart. Circ. Physiol. 1997. V. 273. P. H2604 - H2612.
  15. Reed R.K., Laurent U.B. Turnover of hyaluronan in the microcirculation // Am. Rev. Respir. Dis. 1992. V. 146 (5 Pt 2). P. 37 - 39.
  16. Hinghofer-Szalkay H.G., Mekonen W., Rossler A. Schwaberger G., Lamprecht M., Hofmann P. Post-Exercise Decrease of Plasma Hyaluronan: Increased Clearance or Diminished Production - // Physiol. Res. 2002. V. 51. P. 139 - 144.
  17. Финкинштейн Я.Г. Роль осморегулирующей системы в патогенезе отеков // Терапевтический архив. 1990.Т. 62 (12).С. 122 - 124.
  18. Onarheim H., Reed R.K., Laurent T.C. Elevated hyaluronan blood concentrations in severely burned patients // Scand. J. Clin. Lab. Invest. 1991. V. 51(8). P. 693 - 707.
  19. Бычков С.М., Кузьмина С.А. Действие протеогликанов на эритроциты в циркулирующей крови // Бюллетень экспериментальной биологии и медицины. 1993. № 3. С. 240 - 242.
  20. Zimmerman E., Geiger B., Addadi L.Initial Stages of Cell-Matrix Adhesion Can Be Mediated and Modulated by Cell-Surface Hyaluronan // Biophysical Journal. 2002. V. 82. P. 1848 - 1857.
  21. Aruffo A., Stamenkovic I., Melnick M., Underhill C.B., Seed B.CD44 is the principal cell surface receptor for hyaluronate // Cell. 1990. V. 61. P. 1303 - 1313.
  22. Telen M.J. Erythrocyte adhesion receptors: blood group antigens and related molecules // Transfus. Med. Rev. 2005. V. 19 (1). P. 32 - 44.
  23. Nunomura W., Takakuwa Y, Tokimitsu R., Krauss S.W., Kawashima M., Mohandas N. Regulation of CD44-Protein 4.1 Interaction by Ca2+ and Calmodulin Implications for mo­dulation of CD44- Ankyrin Interaction // Journal of Biological Chemistry. 1997. V. 272 (48). P. 30322-30328.
  24. Ihanus E., Uotila L.M., Toivanen A., Varis M., Gahmberg C.G. Red-cell ICAM-4 is a ligand for the monocyte /macrophage integrin CD11c/ CD18: characterization of the binding sites on ICAM-4 // Blood. 2007. V. 109 (2). P. 802 - 810.
  25. Telen M.J. Red blood cell surface adhesion molecules: their possible roles in normal human physiology and disease // Semin Hematol. 2000. V. 37. P. 130 - 142.
  26. Le Boeuf R.D., Raja R.H., Fuller G. M., Weigel P.H. Human Fibrinogen Specifically Binds Hyaluronic Acid // The Journal of Biological Chemistry. 1986. V. 261 (27).P. 12586 - 12592.
  27. Neu B., Sowemimo-Coker S. O., Meiselman H. J.Cell-Cell Affinity of Senescent Human Erythrocytes // Biophys. J. 2003. V. 85(1). P. 75 - 84.
  28. Di Michele S., Ericson M., Sillen U., Engel J.A., Soderpalm B.The role of catecholamines in desmopressin induced locomotor stimulation // J. Neural. Transm. 1998. V. 105. P. 1103 - 1115.
  29. Тихомирова И.А., Муравьёв А.В. Влияние катехоламинов на процесс агрегатообразования эритроцитов // Российский физиологический журнал им. И.М. Сеченова. 2004. Т. 90 (8). C. 150.