Mechanism of damage to platelet and erythrocyte hemostasis  in rats with prolonged hypokinesia

S. L. Popel’; О. V. Kryzаnivskaya; V. M. Zhurakіvskyi; R. Y. Chovhan; U. N. Dutchak; О. О. Klipich; Y. I. Klipich; T. V. Кnyazevich-Chorna; А. V. Sіnіtsа; N. О. Zemskaya; I. V. Melnik; Y. N. Yatciv; E. Y. Lapkovskiy; Y. V. Lutckiy; N. I. Schovkova

doi:10.15421/021722

S. L. Popel’ Precarpathian National University named after V. Stefanik http://orcid.org/0000-0002-2161-535X
О. V. Kryzаnivskaya Precarpathian National University named after V. Stefanik http://orcid.org/0000-0003-4934-3840
V. M. Zhurakіvskyi Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-8628-5507
R. Y. Chovhan Precarpathian National University named after V. Stefanik http://orcid.org/0000-0003-4168-1773
U. N. Dutchak Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-3715-5650
О. О. Klipich Ivano-Frankivsk National Medical University http://orcid.org/0000-0001-9610-2383
Y. I. Klipich Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-8446-3277
T. V. Кnyazevich-Chorna Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-3497-2858
А. V. Sіnіtsа Precarpathian National University named after V. Stefanik http://orcid.org/0000-0001-6608-919X
N. О. Zemskaya Precarpathian National University named after V. Stefanik http://orcid.org/0000-0002-8169-9954
I. V. Melnik Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-2586-5217
Y. N. Yatciv Precarpathian National University named after V. Stefanik http://orcid.org/0000-0003-2474-0401
E. Y. Lapkovskiy Precarpathian National University named after V. Stefanik http://orcid.org/0000-0002-7717-2236
Y. V. Lutckiy Precarpathian National University named after V. Stefanik http://orcid.org/0000-0003-3940-1349
N. I. Schovkova Ivano-Frankivsk National Medical University http://orcid.org/0000-0002-2248-6297

Keywords: hypokinesia, blood platelet, erythrocytes, hemostasis, ultrastructure

Abstract

The aim of the study was to determine the morphological changes in the cellular elements of blood in rats of different ages under conditions of prolonged hypokinesia. Research into the structural and functional properties of platelets and erythrocytes was carried out by electron microscope and by biochemical methods in 90 mature male rats aged 2, 12 and 24 months. We found that in young (2 month animals) there was a significant increase in the relative content of activated platelets while the normal content of aggregated and degranulated forms with the appearance of single platelets was maintained with an imbalance of alpha and delta granules. In 12-month-old animals, platelet hemostasis disorders were manifested by a significant increase in the relative content of activated platelets (by 125.8–134.7%) with an increase in aggregated and degranulated forms, the appearance of numerous platelets with an imbalance of alpha- and delta-granules, and reduction of mitochondria (by 24.9–27.8%). In 24 month old animals there was a sharp violation of platelet hemostasis due to a significant increase in the content of activated, degranulated and aggregated platelets, the release of the majority of granules, the development of intravascular platelet hyperactivation, an increase in the number of reversible and irreversibly transformed erythrocytes, an increase in the level of aggregation, in particular the appearance of complex cellular aggregates and bizarre forms of red blood cells. The greatest degree of manifestation of morpho-functional changes was revealed in animals aged 24 months, with relative stability of the hemostasis system in 2 and 12 month old animals. Our results showed that irrespective of age, the degree of disturbance of platelet-erythrocyte hemostasis rose as the period of hypokinesia increased and also depended on the increase in the level of serum creatinine. Taken together, intravascular platelet hyperactivation, an imbalance in the content of all types of granules, the transformation of surface cytoarchitectonics of erythrocytes, and the formation of platelet aggregates may play the role of an early predictor of the development of hypokinetic disease

References

Abrams, C. S. (2007). The yin-yang of platelet granules. Blood, 111(3), 979–979.

Arnold, D. M. (2013). A platelet cover-up. Blood, 122(3), 307–309.

Ali, S. F. (2015) Influence of different methods preparation on platelet activation in stored platelet concentrates. Journal of Blood Disorders and Transfusion, 6(3), 279–285.

Bennett, S. T. (2014). Validation of hemostasis assays, analyzers, and reagents. In: Laboratory Hemostasis. Springer, New York.

Blair, P. (2009). Platelet α-granules: Basic biology and clinical correlates. Blood Reviews, 23(4), 177–189.

Bouchard, B. A., Krudysz-Amblo, J. & Butenas, S. (2012). Platelet tissue factor is not expressed transiently after platelet activation. Blood, 119(18), 4338–4339.

Delano, M. J., Rizoli, S. B., Rhind, S. G., Cuschieri, J., Junger, W., Baker, A. J., Dubick, M. A., Hoyt, D. B., & Bulger, E. M. (2015). Prehospital resuscitation of traumatic hemorrhagic shock with hypertonic solutions worsens hypocoagulation and hyperfibrinolysis. Shock, 44(1), 25–31.

Duan, K., Yu, W., Lin, Z., Tan, S., Bai, X., Xu, L., Dong, Y., & Li, N. (2014). A time course study of acute traumatic coagulopathy prior-resuscitation: From hypercoagulation-hypocoagulation caused by hypoperfusion? Transfusion and Apheresis Science, 50(3), 399–406.

Falco, S., Bruno, B., Maurella, C., Bellino, C., D’Angelo, A., Gianella, P., Tarducci, A., Zanatta, R., & Borrelli, A. (2012). In vitro evaluation of canine hemostasis following dilution with hydroxyethyl starch (130/0.4) via thromboelastometry. Journal of Veterinary Emergency and Critical Care, 22(6), 640–645.

Falet, H. (2012). Platelet size: Finding the right balance. Blood, 119(12), 2402–2403.

Freedman, J. E. (2011). A platelet transcriptome revolution. Blood, 118(14), 3760–3761.

Gainutdinov, K. L., Andrianov, V. V., Iyudin, V. S., Yurtaeva, S. V., Jafarova, G. G., Faisullina, R. I., & Sitdikov, F. G. (2013). EPR study of nitric oxide production in rat tissues under hypokinesia. Biophysics, 58(2), 203–205.

Gainutdinov, K. L., Faisullina, R. I., Andrianov, V. V., Gilmutdinova, R. I., Iyudin, V. S., Jafarova, G. G., & Sitdikov, F. G. (2013). Nitric oxide level in the rat tissues increases after 30-day hypokinesia: Studies by electron paramagnetic resonance (EPR) spectroscopy. Bulletin of Experimental Biology and Medicine, 154(5), 635–637.

Greinacher, A. (2011). Platelet activation by heparin. Blood, 117(18), 4686–4687.

Hayward, C. P. M. (2011). Diagnostic evaluation of platelet function disorders. Blood Reviews, 25(4), 169–173.

Huang, Y., Joshi, S., Xiang, B., Kanaho, Y., Li, Z., Bouchard, B. A., Moncman, C. L., & Whiteheart, S. W. (2016). Arf6 controls platelet spreading and clot retraction via integrin Iib 3 trafficking. Blood, 127(11), 1459–1467.

Jaeger, D. & Jung, R. (2015). Hypokinesia model. In: Encyclopedia of computational neuroscience, 1417–1417. Springer, New York.

Juravlyova, O. A., Markin, A. A., Kuzichkin, D. S., Loginov, V. I., Zabolotskaya, I. V., & Vostrikova, L. V. (2016). Dynamics of oxidation stress markers during long-term antiorthostatic hypokinesia: A retrospective study. Human Physiology, 42(1), 79–83.

Kasirer-Friede, A., Kang, J., Kahner, B., Ye, F., Ginsberg, M. H., & Shattil, S. J. (2014). ADAP interactions with talin and kindlin promote platelet integrin IIb 3 activation and stable fibrinogen binding. Blood, 123(20), 3156–3165.

Kitchen, S., & Makris, M. (2010). Laboratory tests of hemostasis. In: Practical hemostasis and thrombosis. Blackwell Publishing Ltd.

Kobro, M. (2009). Investigations of adrenalin concentration blood. Acta Medica Scandinavica, 125(1), 1–7.

Korneychuk, S., Turner, S., Abakumov, A., & Verbeeck, J. (2016). Determination of the platelet structure in natural diamond by ADF-STEM. European Microscopy Congress, Proceedings, 331–332.

Krause, D. S. (2016). An oxidase road-platelet adhesion. Blood, 127(11), 1386–1386.

Lazarus, A. H. (2010). IVIg conducts DC-platelet nuptials. Blood, 116(23), 4740–4741.

Leavitt, A. D. (2007). What for platelet factor 4? Blood, 110(4), 1090–1090.

Lenting, P. J. & Denis, C. V. (2013). Platelet von Willebrand factor: Sweet resistance. Blood, 122(25), 4006–4007.

Leytin, V. (2012). Apoptosis in the anucleate platelet. Blood Reviews, 26(2), 51–63.

Lieberman, L., Bercovitz, R. S., Sholapur, N. S., Heddle, N. M., Stanworth, S. J., & Arnold, D. M. (2014). Platelet transfusions for critically all patients with thrombocytopenia. Blood, 123(8), 1146–1151.

Lutfi, M. F. (2016). Diagnostic accuracy of resting left ventricular akinesia/ hypokinesia in predicting abnormal coronary angiography. BMC Cardiovascular Disorders, 16(1), 137–140.

Makáry, A., Pataki, M., Tóth, E., & Lusztig, G. (1987). The effect of hypoxia and hypokinesia on prostacyclin (PGI2) production of vessel wall. Experimental pathology, 32(4), 251–253.

Marcus, A. J. (2012). New approaches for measurement of platelet reactivity. Blood, 119(15), 3378–3379.

Marks, M. S. (2012). SNA Ring platelet granule secretion. Blood, 120(12), 2355–2357.

Michelson, A. D. (2013). Gray platelet syndrome. Blood, 121(2), 250–250.

Mio, K., Sato, M., & Sato, C. (2016). Structural biology and electron microscopy. Springer Protocols Handbooks.

Naik, M. U., Caplan, J. L., & Naik, U. P. (2013). Junctional adhesion molecule-A suppresses platelet integrin IIb 3 signaling by recruiting Csk the integrin-c-Src complex. Blood, 123(9), 1393–1402.

Neelamegham, S. (2012). The computing platelet: Integrating environmental cues. Blood, 120(1), 3–4.

Peter, K. (2010). Proteomics unravels platelet function. Blood, 115(20), 4008–4009.

Pitchford, S. C. (2015). The stop clock of platelet activation. Blood, 126(24), 2538–2539.

Rao, A. K. (2013). Spotlight on FLI1, RUNX1, and platelet dysfunction. Blood, 122(25), 4004–4006.

Rayes, J., & Watson, S. P. (2015). Platelet GPVI repairs its own damage. Blood, 126(8), 933–934.

Ruggeri, Z. M. (2015). Platelet GPIb: Sensing force and responding. Blood, 125(3), 423–424.

Stogov, M. V. (2009). Creatine metabolism in skeletal muscles during hypokinesia. Bulletin of Experimental Biology and Medicine, 148(1), 26–28.

Tseilikman, V. E., Pankov, N. E., Pankova, N. A., Filimonova, T. A., Sinitskii, A. I., Kozochkin, D. A., & Tseilikman, O. B. (2013). Correlation between circulating corticosterone and protein carbonylation in the liver after short-term hypokinesia. Bulletin of Experimental Biology and Medicine, 156(2), 188–190.

Vitkovsky, Y., & Strambovskaya, N. (2014). Platelet functions in healthy persons with genetic polymorphism of GPIA(C807T), GPIIIA(T1565C), GPIBA(C434T), P2RY12(H1/H2), SELP(G1087A) platelet receptors. Thrombosis Research, 133, 83.

Ware, J. (2012). Fragmenting the platelet-reduce metastasis. Blood, 120(14), 2779–2780.

White, J. G. (2010). Platelet interior imaging technologies. Blood, 116(26), 6150–6151.

Whiteheart, S. W. (2011). Platelet granules: Surprise packages. Blood, 118(5), 1190–1191.

Zhu, J., Zhu, J., Bougie, D. W., Aster, R. H., & Springer, T. A. (2015). Structural basis for quinine-dependent antibody binding-platelet integrin IIb 3. Blood, 126(18), 2138–2145.

Zorbas, Y. G., Deogenov, V. A., Merkov, P. L., & Federenko, Y. F. (2012). Chronic periodic fluid redistribution effect on muscle calcium in healthy subjects during prolonged hypokinesia. The Journal of Physiological Sciences, 62(3), 233–239.

Mechanism of damage to platelet and erythrocyte hemostasis in rats with prolonged hypokinesia

Abstract

References

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