PECULIARITIES OF THE IMMUNE SYSTEM RESPONSE IN THE EARLY PERIOD AFTER THE MASSIVE BLOOD LOSS AND LIMB ISCHEMIA-REPERFUSION

Volotovska N. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Under various environmental influences, the immune system responds sensitively. Implementation a protective function, however, it can also cause autoimmune processes, which will only aggravate the underlying disease, especially in conditions of already activated systemic response to inflammation. Thus, imbalance in the immune system can be one of the factors of the «vicious circle» that occurs on the background of a blood loss, when circulating immune complexes can contribute to hepato-renal syndrome. However, these concepts remain insufficiently studied in the conditions of combining massive blood loss with ischemia-reperfusion. The aim of the study – to know the dynamics of the concentration of circulating immune complexes, as well as the patterns of violations of humoral immunity due to the systemic effects of limb ischemia-reperfusion and massive blood loss. Object and methods of research. The work was performed on white nonlinear male rats, and the object of study was the course of massive blood loss under conditions of ischemia-reperfusion of the limb. In animals, limb ischemia-reperfusion was simulated by applying an elastic tourniquet to the upper third of the thigh according to the established method, massive blood loss from the femoral vein by femoral vein puncture was simulated, and in the third group these two interventions were combined. Results. The simulated interventions are characterized by pronounced disorders of humoral immunity, which are accompanied by accumulation in the serum of the CІC and the development of dizimunoglobulinemia. The content of Ig A in the conditions of blood loss combined with limb ischemia-reperfusion (EG-3) was characterized by two periods of growth on the 1 and 7 days after the intervention and was higher compared to other experimental groups. The content of Ig M in EG-3 increased on the 1 h after reperfusion (by 53.3% compared with the control), but later remained at the lowest level. The content of Ig G increased in all study groups mainly up to the 3 day with a subsequent decrease. In EG-3 the index on the 14 day became significantly lower than the control (p <0.05). Conclusions. At all stages of development of traumatic disease there is a significant increase in the titer of immunoglobulins A, M, G with an predominance in the first hour after reinfusion, as well as an increase on the 7 day of experiment, that confirms a strong antigenic load involving both primary and secondary immune response in pathogenesis of post-traumatic changes. The peculiarity was that the combination of limb ischemia-reperfusion with blood loss can inhibit the formation of immunoglobulins.

massive blood loss, mechanical trauma, ischemia-reperfusion, circulating immune complexes, immunoglobulins.

1. Inaba K, Siboni S, Resnick S, Zhu J, Wong MD, Haltmeier T, et al. Tourniquet use for civilian extremity trauma. J Trauma Acute Care Surg. 2015 Aug;79(2):232-237:26218691. DOI: 10.1097/TA.0000000000000747.
2. Kauvar DS, Dubick MA, Walters TJ, Kragh JF Jr. Systematic review of prehospital tourniquet use in civilian limb trauma. J Trauma Acute Care Surg. 2018 May;84(5):819-825:29432381. DOI: 10.1097/TA.000000000 0001826.
3. Yavorska IV. Vplyv hostroi krovovtraty, uskladnenoi ishemiieiu-reperfuziieiu kintsivky na dynamiku pokaznykiv enzymnoi lanky antyoksydantnoho zakhystu v selezintsi ta yoho korektsiia karbatsetamom. Zdobutky klinichnoi i eksperymentalnoi medytsyn. 2021;2:195- 202. DOI: 10.11603/1811-2471.2021.v.i2.12225. [in Ukrainian].
4. Ardasheva EI. Razumov PS. Dolgova SG. Vliyaniye perftorana na protsessy perekisnogo okisleniya lipidov v golovnom mozge i myagkikh tkanyakh krys pri tyazheloy kompressionnoy travme. Biomeditsinskiy zhurnal. 2004;5:151-153. [in Russian].
5. Henyk SM, Symchych AV. Reperfuziinyi syndrom pislia revaskuliaryzatsii ishemii nyzhnikh kintsivok. Sertse i sudyny. 2016;3:104-108. [in Ukrainian].
6. Burianov OA, Strafun SS, Shlapak IP, Laksha AM, Halushko OA, Yarmoliuk YuO, et al. Vohnepalni poranennia kintsivky. Kyiv; 2015. 46 s. [in Ukrainian].
7. Volotovska NV, Hudyma AA. Osoblyvosti hepatorenalnoi reaktsii na tli eksperymentalnoho ishemichno-reperfuziinoho syndromu. Visnyk problem biolohiyi i medytsyny. 2020;2(156):86-9. [in Ukrainian].
8. Kozak DV. Dynamika vmistu tsyrkuliuiuchykh imunnykh kompleksiv ta imunohlobuliniv u vidpovid u vidpovid na politravmu v eksperymenti. Klinichna khirurhiia. 2013;12(852):76-78. [in Ukrainian].
9. Kazmirchuk V, Kovalchuk LV. Klinichna imunolohiia i alerholohiia. Vinnytsia: Nova knyha; 2006. 504 s. [in Ukrainian].
10. Nebylitsin YuS, Lazuko SS, Kutko EA. Sindrom ishemii-reperfuzii nizhnikh konechnostey. Vestnik VGMU. 2018;17(6):18-31. Dostupno: https:// cyberleninka.ru/article/n/sindrom-ishemii-reperfuzii-nizhnih-konechnostey. [in Russian]
11.  Wall PL, Duevel DC, Hassan MB, Welander JD, Sahr SM, Buising CM. Tourniquets and oklusion: the pressure of design. Military Medicine. 2013;178(5):578-587.
12. Chernushenko EF, Kogosova LS. Immunologicheskiye metody issledovaniya v klinike. K.: Zdorov’ya; 1978. 160 s. [in Russian].
13. Vytiah z zakonu Ukrainy «Pro zakhyst tvaryn vid zhorstokoho povodzhennia». Morfolohiia. 2010;IV(2):12-15. [in Ukrainian].
14. Gorlov IV, Slozhenkina MI, Mosolova NI, Belik SN, Levakhin VI. Izmeneniye struktury vnutrennikh organov krys. poluchavshikh kormovuyu dobavku s aktibakterialnymi komponentami. Vestnik Rossiyskoy akademii selskokhozyaystvennykh nauk. 2015:5:38-32. [in Russian].
15. Belik SN, Zhukova TV, Svintukhovskiy OA, Kharagurgiyeva IM, Avetisyan ZI. Sravnitelnyy analiz pokazateley belkovogo obmena u krys pri otsenke kachestva i bezopasnosti produktov zhivotnovodstva. Zdorovye i obrazovaniye v KhKhI veke. 2016;18(6):52-55. [in Russian].
16. Turer AT, Hill JA. Pathogenesis of myocardial ischemia-reperfusion injury and rationale for therapy. Am J Cardiol. 2010 Aug 1;106(3):360- 368. DOI: 10.1016/j.amjcard.2010.03.032.
17. Zhang J, Zhang J, Yu P, Chen M, Peng Q, Wang Z, et al. Remote Ischaemic Preconditioning and Sevoflurane Postconditioning Synergistically Protect Rats from Myocardial Injury Induced by Ischemia and Reperfusion Partly via Inhibition TLR4/MyD88/NF-κB Signaling Pathway. Cell Physiol Biochem. 2017;41(1):22-32.
18. Rodrigues SF, Granger DN. Role of blood cells in ischaemia-reperfusion induced endothelial barrier failure. Cardiovasc Res. 2010 Jul 15;87(2):291-9. DOI: 10.1093/cvr/cvq090.
19. Khatri R, McKinney AM, Swenson B, Janardhan V. Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke. Neurology. 2012;79(13):52-7. DOI: 10.1212/WNL.0b013e3182697e70.
20. McDonagh PF, Hokama JY, Copeland JG, Reynolds JM. The blood contribution to early myocardial reperfusion injury is amplified in diabetes. Diabetes. 1997 Nov;46(11):1859-1867. DOI: 10.2337/diab.46.11.1859.
21. Chatauret N, Badet L, Barrou B, Hauet T. Ischemia-reperfusion: From cell biology to acute kidney injury. Prog Urol. 2014 Jun;24(1):4-12. DOI: 10.1016/S1166-7087(14)70057-0.
22. Uhlmann D, Armann B, Gaebel G, Ludwig S, Hess J, Pietsch UC, et al. Endothelin A receptor blockade reduces hepatic ischemia/reperfusion injury after warm ischemia in a pig model. J Gastrointest Surg. 2003 Mar-Apr;7(3):331-9. DOI: 10.1016/s1091-255x(02)00417-1.
23. Fitridge R, Thompson M, editors. Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists. Adelaide (AU): University of Adelaide Press; 2011. 587 p.
24. Al-Harz W, Babiker F. Acute intravenous infusion of Immunoglobulins protects against myocardial ischemia-reperfusion injury through inhibition of caspase-3. Cell Physiol Biochem. 2017;42:2295-2306. DOI: 10.1159/ 000480002.
25. Festal EI, Nosenko VM, Populiakh OI. Nevidkladna terapiia porushen imunitetu v hostromu periodi opikovoi khvoroby. Medytsyna neotlozhnukh sostoianyi. 2010;5(30):77-82. [in Ukrainian].
26. Nikulin BA. Otsenka i korrektsiya immunnogo statusa. M: GEOTAR-MEDIA; 2007. 367 s. [in Russian].
27. Zhang M, Takanashi K, Alikot AM, Vorup-Jensen T, Kessler B, Thiel S, et al. Activation of the Lectin pathway by natural IgM in a model of ischemia/reperfusion injury. J Immunol. 2006;177:4727-4734. DOI: 10.4049/jimmunol.177.7.4727.

«Bulletin of problems biology and medicine» Issue 4 (162), 2021 year, 109-114 pages, index UDK 616.718-001.5:616.137/.147-005/1:616.748-005.4]-089.814-092.19

10.29254/2077-4214-2021-4-162-109-114