ФИЗИОЛОГИЧЕСКИЕ МЕХАНИЗМЫ ДЕЙСТВИЯ САЛИЦИЛАТОВ НА СЕРДЕЧНО-СОСУДИСТУЮ СИСТЕМУ
PDF

Ключевые слова

ацетилсалициловая кислота
кардиотропные эффекты
центральная гемодинамика
микроциркуляция
сосудисто-тромбоцитарный гемостаз
фибринолиз

Как цитировать

Чуян, Е. Н., Миронюк, И. С., Черетаев, И. В., Раваева, М. Ю., & Гришина, Т. В. (2021). ФИЗИОЛОГИЧЕСКИЕ МЕХАНИЗМЫ ДЕЙСТВИЯ САЛИЦИЛАТОВ НА СЕРДЕЧНО-СОСУДИСТУЮ СИСТЕМУ. Российский физиологический журнал им. И. М. Сеченова, 107(3), 288–311. https://doi.org/10.31857/S0869813921030055

Аннотация

В современной литературе четко прослеживается возросший интерес к изучению биологических и терапевтических эффектов салицилатов. Крупные клинические испытания продемонстрировали эффективность ацетилсалициловой кислоты (АСК) и ее комплексных соединений в лечении и профилактике ишемической болезни сердца, хронической сердечной недостаточности, гипертонии и других заболеваниях, что позволяет оценить широту благоприятных эффектов, оказываемых АСК на функционирование сердечно-сосудистой системы (ССС) и констатировать отсутствие в ближайшие годы других равноценных лекарственных средств. Важнейшим направлением остается расширение и усиление известной терапевтической активности (антипиретическая, анальгезирующая, противовоспалительная, антиоксидантная, антидепрессантная, противомигренозная, анксиолитическая и др.) на фоне снижения и/или ликвидации побочных эффектов, поскольку АСК занимает лидирующее положение среди всех нестероидных противовоспалительных препаратов по объёмам применения и одно из первых мест по количеству побочных эффектов. Перспективным для решения этой проблемы является создание комплексных соединений салицилатов, поскольку при образовании новых координационных соединений на их основе возможно возникновение новых полезных биологических свойств, а также усиление физиологических эффектов, характерных для АСК, что поможет решить проблему снижения побочных эффектов, резистентности к терапии аспирином и повышения терапевтического потенциала исходного соединения для получения эффективных лекарственных препаратов нового поколения.

В статье обобщены и проанализированы обширные сведения о физиологических и молекулярных механизмах действия АСК и ее производных на ССС в норме и патологии, в том числе на различные физиологические и биохимические звенья гомеостаза организма: вазорегулирующую функцию эндотелия сосудов, сосудисто-тромбоцитарный гемостаз; фибринолиз; процессы свободнорадикального окисления и антиоксидантной защиты; циклооксигеназный и липоксигеназный пути окисления арахидоновой кислоты; молекулярные маркеры процессов воспаления (простагландины; про- и противовоспалительные цитокины; противовоспалительные липидные медиаторы). Подробно изложены и проанализированы имеющиеся данные литературы и результаты собственных экспериментальных исследований о влиянии салицилатов на центральную гемодинамику и тканевую микроциркуляцию. Сделан вывод о перспективности исследований количественных и качественных изменений микроциркуляторных процессов под влиянием АСК и ее производных, что позволит уточнить механизмы биологического действия этих соединений на ССС.

https://doi.org/10.31857/S0869813921030055
PDF

Литература

Григорьева А.С. Оптимизация фармакотерапевтической активности биометаллов при комплексообразовании с НПВП. Микроэлементы в медицине. 2(1): 17-22. 2000. [Grigorieva A.S. The optimization of farmacotherapeutic activity upon the complex formation between biometals and non-steroid anti- inflammatory compounds. Trace Elements in Medicine. 2(1): 17–22. 2000. (In Russ)].

Bica K., Rijksen C., Nieuwenhuyzena M., Rogers R.D. In search of pure liquid salt forms of aspirin: ionic liquid approaches with acetylsalicylic acid and salicylic acid. Phys. Chem. 12: 2011–2017. 2010. https://doi.org/10.1039/b923855g

Awtry E.H., Loscalzo J. Aspirin. Circulation. 101(10): 1206–1218. 2000.

Rainsford K.D. Aspirin and related drugs. Sheffield. UK. CRC Press. 2004.

Guan X., Shao F., Xie X., Chen L., Wang W. Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine. Pharmacol. Biochem. Behav. 124: 361–366. 2014. https://doi.org/10.1016/j.pbb.2014.07.002

Bayram F., Reis R., Tunçer B., Sipahi H. The Importance of the Structural Similarity of Drugs Used for Depression and Inflammation. Two Comorbid Diseases. Curr. Topics Med. Chem. 18(16): 1416–1421. 2018. https://doi.org/10.2174/1568026618666180821144704

Tauseef M., Sharma K.K., Fahim M. Aspirin restores normal baroreflex function in hypercholesterolemic rats by its antioxidative action. Eur. J. Pharmacol. 556(1-3): 136–143. 2007. https://doi.org/10.1016/j.ejphar.2006.11.029

Brunello N., Alboni S., Capone G., Benatti C., Blom J.M., Tascedda F., Kriwin P., Mendlewicz J. Acetylsalicylic acid accelerates the antidepressant effect of fluoxetine in the chronic escape deficit model of depression. Internat. Clin. Psychopharmacol. 21(4): 219–225. 2006. https://doi.org/10.1097/00004850-200607000-00004

Almeida O.P., Flicker L., Yeap B.B., Alfonso H., McCaul K., Hankey G.J. Aspirin decreases the risk of depression in older men with high plasma homocysteine. Translat. Psychiatry. 2(8): 151. 2012. https://doi.org/10.1038/tp.2012.79

Черетаев И.В., Хусаинов Д.Р., Коренюк И.И., Чуян Е.Н., Раваева М.Ю., Шульгин В.Ф., Гусев А.Н. Нейротропные эффекты салицилатов: физиологические механизмы. Ученые записки Крымского федер. универ. им В.И. Вернадского. Биология. Химия. 5(4): 201–213. 2019. [Cheretaev I.V., Khusainov D.R., Koreniuk I.I., Chuyan E.N., Ravaeva M.Yu., Shulgin V.F., Gusev A.N. Neurotropic effects of salycylates: physiological mechanism. Scientific Notes of Taurida V.I. Vernadsky National Univer. Series: Biology. Chemistry. 5(4): 201–213.2019 (In Russ)].

Arkhipova O.V., Grishin S.N., Sitdikova G.F., Zefirov A.L. The presynaptic effects of arachidonic acid and prostaglandin E2 at the frog neuromuscular junction. Neurosci. Behav. Physiol. 36(3): 307–312. 2006. https://doi.org/10.1007/s11055-006-0017-9

Angelova P., Müller W. Oxidative modulation of the transient potassium current IA by intracellular arachidonic acid in rat CA1 pyramidal neurons. Eur. J. Neurosci. 23(9): 2375–2384. 2006. https://doi.org/10.1111/j.1460-9568.2006.04767.x

Rubner G., Bensdorf K., Wellner A., Bergemann S., Gust R. Synthesis, Characterisation and Biological Evaluation of Copper and Silver Complexes based on Acetylsalicylic Acid. Arch. Pharm. Chem. Life Sci. 344: 684–688. 2010

Gilligan M.M, Gartung А., Sulciner M.L., Norris P.C., Huang S., Kieran M.W., Serhan C.N. Aspirin-triggered proresolving mediators stimulate resolution in cancer. Proc. Natl. Acad. Sci. 116(13): 6292–6297. 2019. https://doi.org/10.1073/pnas.1804000116

Altinoz M.A., Elmaci I., Cengiz S., Emekli-Alturfan E., Ozpinar A. From epidemiology to treatment: Aspirin's prevention of brain and breast-cancer and cardioprotection may associate with its metabolite gentisic acid. Chemico-Biol. Interact. 291: 29–39. 2018. https://doi.org/10.1016/j.cbi.2018.05.016

Rolka D.B., Fagot-Campagna A., Narayan K.M. Aspirin use among adults with diabetes: estimates from the Third National Health and Nutrition Examination Survey. Diabetes Care. 24(2): 197–201. 2001. https://doi.org/10.1001/archinte.164.22.2492

Terry M.B., Gammon M.D., Zhang F.F., Tawfik H., Teitelbaum S.L., Britton J.A., Subbaramaiah K., Dannenberg A.J., Neugut A.I. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. J.A.M.A. 291(20): 2433 – 2440. 2004. https://doi.org/10.1001/jama.291.20.2433

Doutremepuich C., Aguejouf O, Desplat V., Eizayaga F.X. Aspirin therapy: an attempt to explain the events of prothrombotic complications after treatment discontinuation. Thrombosis and Haemostasis. 103(1): 171–180. 2010. http://dx.doi.org/10.1160/TH09-07-0506

Patrignani P., Patrono C. Aspirin and cancer. J. Am. College Cardiol. 68(9): 967–976. 2016. https://doi.org/10.1016/j.jacc.2016.05.083

Jacobs E.J., Newton C.C., Gapstur S.M., Thun M.J. Daily aspirin use and cancer mortality in large US cohort. J. Natl. Cancer Inst. 104(16): 1208–1217. 2012. https://doi.org/10.1093/jnci/djs318

McNeil J.J., Gibbs P., Orchard S.G., Lockery J.E., Bernstein W.B., Cao Y., Ford L., Haydon A., Kirpach B., Macrae F., McLean C., Millar J., Murray A.M., Nelson M.R., Polekhina G., Reid C.M., Richmond E., Rodríguez L.M., Shah R.C., Tie J., Umar A., van Londen G.J., Ronaldson K., Wolfe R., Woods R.L., Zalcberg J., Chan A.T., ASPREE Investigator Group. Effect of aspirin on cancer incidence and mortality in older adults. J. Natl. Cancer Inst. 1–24. 2020. http://doi.org/10.1093/jnci/djaa114

Вельц Н.Ю., Журавлева Е.О., Букатина Т.М., Кутехова Г.В. Нестероидные противовоспалительные препараты: проблемы безопасности применения. Безопасность и риск фармакотерапии. 6(1): 11–18. 2018. [VeltsN.Yu., Zhuravleva E.O., Bukatina T.M., Kutekhova G.V. Non steroidalanti-inflammatory drugs: problems of safe use. Safety and Risk Pharmacother. 6(1): 11–18. 2018. (In Russ)]. https://doi.org/10.30895/2312-7821-2018-6-1-11-18

Венгеровский А.И., Батурина Н.О., Саратиков А.С. Синдром Рейе – тяжёлое осложнение терапии салицилатами. Экспер. и клин. фармакол. 63(2): 76–80. 2000. [Vengerovsky A.I., Baturina N.O., Saratikov A.C. Reye's Syndrome – a serious complication of treatment with salicylates. Exp. and Clin. Pharmacol. 63(2): 76–80. 2000. (In Russ)].

Mogilevskaya E., Demin O., Goryanin I. Kinetic model of mitochondrial krebs cycle: unraveling the mechanism of salicylate hepatotoxic effects. J. Biol. Physics. 32(3-4): 245–271. 2006. https://doi.org/10.1007/s10867-006-9015-y

Sanderson S., Emery J., Baglin T., Kinmonth A.L. Narrative review: Aspirin resistance and its clinical implications. Ann. Int. Med. 142(5): 370–380. 2005.

Lanza F.L. A guide line for the treatment and prevention of NSAID–inducedulcers. Am. J. Gastroent. 93: 2037–2046. 1998.

Chan F.K., Chung S.C., Suen B.Y., Lee Y.T., Leung W.K., Leung V.K., Wu J.C., Lau J.Y., Hui Y., Lai M.S., Chan H.L., Sung J.J. Preventing recurrent upper gastrointestinal bleeding in patient with Helicobacter pylori infection who are taken low dose aspirin or naproxen. N. Engl. J. Med. 344(13): 967–973. 2001. https://doi.org/10.1056/nejm200103293441304

Lai K.C., Lam S.K., Chu K.M., Wong B.C., Hui W.M., Hu W.H., Lau G.K., Wong W.M., Yuen M.F., Chan A.O., Lai C.L., Wong J. Lansoprazole for the prevention of recurrences of ulcer complications from long term low dose aspirin use. N. Engl. J. Med. 346(26): 2033–2038. 2002. https://doi.org/10.1056/NEJMoa012877

Fadeyi O.O., Obafemi C.A., Adewunmi C.O., Iwalewa E.O. Antipyretic, analgesic, anti-inflammatory and cytotoxic effects of four derivatives of salicylic acid and anthranilic acid in mice and rats. African J. Biotechnol. 3(8): 426–431. 2004. https://doi.org/10.5897/AJB2004.000-2081

Будрицкий А.М., Ивкин Д.Ю., Оковитый С.В., Ивкина А.С., Суханов Д.С., Дзюба А.С. Составление обзоров по доклиническим исследованиям лекарственных средств на примере висмута субсалицилата. Вестник ВГМУ. 18(3): 16–31. 2019. [Budritsky A.M., Ivkin D.Y., Okovitiy S. V., Ivkina A.S., Sukhanov D.S., Dziuba A.S. Drawing up reviews on preclinical trials of medicines on the example of bismuth subsalicylate. Vestnik VGMU. 18(3): 16–31. 2019. (In Russ)]. https://doi.org/10.22263/2312-4156.2019.3.16

Lewis A.J., Cottney J., Sugrue M.F. The spontaneously contracting pregnant rat uterus as a model for anti-inflammatory drug activity. J. Pharmacy and Pharmacol. 27(5): 375 – 376. 1975. https://doi.org/10.1111/j.2042-7158.1975.tb09461.x

Ignatyev I., Kondratenko Y., Fundamensky V., Kochina T. Synthesis and characterization of cobalt (II) complexes with triethanolamine and succinate and/or nitrate anions. Transition Metal Chemi. 43(2): 127–136. 2018. https://doi.org/ 10.1007/s11243-017-0199-8

Jiang Q.Y., Zhang Y.Z., Lei D.W., Zhong G.Q. Synthesis and application research situation of aspirin complexes. Chem. Intermediates.8: 26–30. 2007.

Yun Y., Chen P., Zheng C.L., Yang Y., Duan W.G., Wang L., He B., Ma J.Q., Wang D.H., Shen Z.Q. Copper-aspirin complex inhibits cyclooxygenase-2 more selectively than aspirin. Yakugaku Zasshi. 127(11): 1869–1875. 2007. https://doi.org/10.1248/yakushi.127.1869

Chohan Z.H., Iqbal M.S., Iqbal H.S., Scozzafava A., Supuran C.T. Transition metal acetylsalicylates and their anti-inflammatory activity. J. Enzyme Inhibition and Med. Chemi. 17(2): 87–91. 2002. https://doi.org/10.1080/14756360290030734

Mohamed F.A., Aly S.A., Abdel-Rahman H.M. Pharmacokinetics and pharmacodynamics evaluation of prepared zinc aspirin suppositories. Bull. Pharm. Sci. 26(2): 187–199. 2003. https://doi.org/10.21608/BFSA.2003.65483

Xue S., Chen S., Wang M., Chen J. Antipyretic and analgesic effects of zinc acetylsalicylate. J. Shenyang Pharmac. Univer. 12(2): 133. 1995.

Korenyuk I.I., Husainov D.R., Shulgin V.F. Effects of Salicylic Acid and Its Salts on Electrical Activity of Neurons of Helix albescens. Neurophysiology. 37: 127-134. 2005. https://doi.org/10.1007/s11062-005-0054-y

Korenyuk I.I., Khusainov D.R., Shulgin V.F. Cobalt and Zinc Salicylates as Functional Analogs of an Initiating Factor in the Molluscan Nervous System. Neurophysiology. 38(1): 9–14. 2006. https://doi.org/10.1007/s11062-006-0020-3

Черетаев И.В., Коренюк И.И., Хусаинов Д.Р. Анализ АТФ-зависимых и кальциевых механизмов в реализации нейротропного действия аспирина и его производных. Успехи совр. естествознания. 4: 64 – 69. 2013. [Cheretaev I.V., Korenyuk I.I., Husainov D.R. Analysis of ATP dependent and calcium mechanisms in implementation neurotropic action of aspirin and its derivatives. Uspehi Sovr. Estestvoznanija. 4: 64 – 69. 2013. (In Russ)].

Yakovchyuk T.V., Katiushyna O.V., Koreniuk I.I., Khusainov D.R., Gamma T.V. Psychotropic effects of aspirin, acetylsalicylate cobalt and acetylsalicylate zinc at various doses. Health. 4(11): 1041–1045. 2012. http://dx.doi.org/10.4236/health.2012.411159

Сheretaev I.V., Korenyuk I.I., Khusainov D.R. ATP-Dependent and Calcium Mechanisms of the Effects of Salicylates on Electrical Potentials in Neurons in the Mollusk Helix Albescens. Neurosci. Behav. Physiol. 46(6): 644 – 651. 2016. https://doi.org/10.1007/s11055-016-0291-0

Чуян Е.Н., Миронюк И.С., Раваева М.Ю., Черетаев И.В., Гришина Т.В. Показатели кардиореспираторной системы крыс при действии ацетилсалициловой кислоты и её комплексных соединений с металлами. Ученые записки Крымского федер. универ. им. В.И. Вернадского. Биология. Химия. 6(2): 267–280. 2020. [Chuyan E.N., Mironyuk I.S., Ravaeva M.Yu., Cheretaev I.V., Grishina T.V. Indicators of the rat cardiorespiratory system under the action of acetylsalicylic acid and its complex compounds with metals. Scient. notes of the Crimean Feder. Univer. after V.I. Vernadsky. Biology. Chemistry. 6(2): 267–280. 2020. (In Russ)]. https://doi.org/ 10.37279/2413-1725-2020-6-2-267-280

Wu R., Lamontagne D., Champlain J. Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation. 105(3): 387–392. 2002. https://doi.org/10.1161/hc0302.102609

ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 2(8607): 349–360. 1988.

Остроумова О.Д. Ацетилсалициловая кислота – препарат номер один для лечения сердечно–сосудистых заболеваний: основные показания к применению, клинические преимущества, эффективные дозы и пути повышения переносимости. Рус. мед. журн. 11(5): 275–281. 2003. [Ostroumova O.D. Acetylsalicylic acid-the number one drug for the treatment of cardiovascular diseases: the main indications for use, clinical benefits, effective doses and ways to increase tolerability. Russ. Med. J. 11(5): 275–281. 2003. (In Russ.)].

Antithrombotic Trialists (ATT) Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta–analysis of individual participant data from randomised trials. Lancet. 373(9678): 1849–1860. 2009. https://doi.org/10.1016/S0140-6736(09)60503-1

Jonathan H.C., Ashish K.K., Shravan K., Yamane D., Levine A., Jackson A.M., McCurdy M., Tabatabai A., Kumar G., Park P., Benjenk I., Menaker J., Ahmed N., Glidewell E., Presutto E., Cain S., Haridasa N., Field W., Fowler J.G., Trinh D., Johnson K.N., Kaur A., Lee A., Sebastian K.M., Ulrich A., Peña S., Carpenter R., Sudhakar S., Uppal P., Fedeles B.T., Sachs A., Dahbour L., Teeter W., Tanaka K., Galvagno S.M., Herr D.L., Scalea T.M., Mazzeffi M.A. Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In Hospital Mortality in Hospitalized Patients with COVID-19. Anesthesia & Analgesia. J. Publ. Ahead of Print. 1–41. 2020. https://doi.org/10.1213/ANE.0000000000005292

Schrör K. Acetylsalicylic acid. Second Edition. John Wiley & Sons. 459. 2016.

Klabunde R. Cardiovascular physiology concept. Lippincott Williams & Wilkins. 243. 2011.

Hybiak J., Broniarek I., Kiryczyński G., Los L.D., Rosik J., Machaj F., Sławiński H., Jankowska K., Urasińska E. Aspirin and its pleiotropic application. Eur. J. Pharmacol. 866: 172–762. 2020. https://doi.org/10.1016/j.ejphar.2019.172762

Dudzinski D.M., Serhan C.N., Golan D.E., Armstrong E.J., Galanter J.M. Pharmacology of eicosanoids. Principles of pharmacology: the pathophysiologic basis of drug therapy. Philadelphia. Lippincott Williams & Wilkins. 627–646. 2004.

Hirashima Y., Nakamura S., Endo S., Kuwayama N., Naruse Y., Takaku A. Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage. Neurochem. Res. 22(10): 1249–1255. 1997. https://doi.org/10.1023/a:1021985030331

Nomura S., Kagawa H., Ozaki Y., Nagahama M., Yoshimura C., Fukuhara S. Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies. Thrombosis Res. 95(5): 205–213. 1999. https://doi.org/10.1016/s0049-3848(99)00024-9

Nguyen T.C., Liu A., Liu Li., Ball C., Choi H., May W.S., Aboulfatova K., Bergeron A.L., Dong J.F. Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis. Haematologica. 92 (1): 121–124. 2007. https://doi.org/10.3324/haematol.10262

Cao W.J., Niiya M., Zheng X.W., Shang D.Z., Zheng X.L. Inflammatory cytokines inhibit ADAMTS-13 synthesis in hepatic stellate cells and endothelial cells. J. Thromb. Haemost. 6(7): 1233–1235. 2008. https://doi.org/10.1111/j.1538-7836.2008.02989.x

Bernando A., Ball C., Nolasco L., Moake J., Dong J. Effect of inflammatory cytokines on the release and cleavage of the endothelial cell-derived ultra large von Willebrand factor multimers under flow. Blood. 104(1): 100–106. 2004. https://doi.org/10.1182/blood-2004-01-0107

Owen C.A., Campbell M.A., Boukedes S.S., Campbell E.G. Inducible binding of bioactive cathepsin G to the cell surface of neutrophils. J. Immunol. 155(12): 5803–5810. 1995.

Gori A.M., Cesari F., Marcucci R., Giusti B., Paniccia R., Antonucci E., Gensini G.F., Abbate R. The balance between pro- and anti-inflammatory cytokines is associated with platelet agreeability in acute coronary syndrome patients. Atherosclerosis. 202(1): 255–262. 2009. https://doi.org/10.1016/j.atherosclerosis.2008.04.001

Кузник Б.И. Цитокины и система гемостаза I. Цитокины и сосудисто-тромбоцитарный гемостаз. Тромбоз, гемостаз и реология. 2: 12–23. 2012. [Kuznik B.I. Cytokines and haemostasis and vascular platelet haemostasis. Thrombosis, hemostasis and rheology. 2: 12–23. 2012. (In Russ)].

Solheim S., Pettersen A.A., Arnesen H., Seljeflot I. No difference in the effects of clopidogrel and aspirin on inflammatory markers in patients with coronary heart disease. Thromb. Haemost. 96(5): 660–664. 2006.

Генадинник А.Г., Нелаева А.А. Влияние аспирина на тромбоцитарное звено гемостаза у пациентов с метаболическим синдромом. Сахарный диабет. (4): 32–34. 2005. [Genadinnik A.G., Nelaeva A.A. Effect of aspirin on platelet hemostasis in patients with metabolic syndrome. Diabetes. (4): 32–34. 2005. (In Russ)]. https://doi.org/10.14341/2072-0351-5963

Sternberg Z., Chichelli T., Sternberg D., Sawyer R., Ching M., Janicke D., Ambrus J.L., Yu J., Munschauer F. Relationship between inflammation and aspirin and clopidogrel antiplatelet responses in acute ischemic stroke. J. Stroke Cerebrovasc. Diseases. 25 (2): 327–334. 2016. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.10.001

Рождественский Д.А. Клиническая фармакология омега-3 полиненасыщенных жирных кислот. Междунар. обзоры: клин. практика и здоровье. 4: 121–134. 2014. [Rozhdestvensky D.A. Clinical pharmacology of omega-3 polyunsaturated fatty acids. Internat. Rev.: Clinical Practice and Health. 4: 121–134. 2014. (In Russ)].

Serhan C.N., Hong S., Gronert K., Colgan S.P., Devchand P.R., Mirick G., Moussignac R.L. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med. 196 (8): 1025–1037. 2002. https://doi.org/10.1084/jem.20020760

Arita M., Bianchini F., Aliberti J., Sher A., Chiang N., Hong S., Yang R., Petasis N.A., Serhan C.N. Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolving. J. Exp. Med. 201(5): 713–722. 2005. https://doi.org/10.1084/jem.20042031

Schwab J.M., Chiang N., Arita M., Serhan C.N. Resolvin E1 and protectin D1 activate inflammation resolution programmes. Nature. 447(7146): 869–874. 2007. https://doi.org/10.1038/nature05877

Arita M., Ohira T., Sun Y.P., Elangovan S., Chiang N., Serhan C.N. Resolvin E1selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J. Immunol. 178(6): 3912–3917. 2007. https://doi.org/10.4049/jimmunol.178.6.3912

Fredman G., Serhan C.N. Specialized proresolving mediator targets for RvE1 and RvD1 in peripheral blood and mechanisms of resolution. Biochemistry. 437(2): 185–197. 2011. https://doi.org/10.1042/BJ20110327

Tjonahen E., Oh S.F., Siegelman J., Elangovan S., Percarpio K.B., Hong S., Arita M., Serhan C.N. Resolvin E2: identification and anti-inflammatory actions: pivotal role of human 5-lipoxygenase in resolvin E series biosynthesis. J. Chem. Biol. 13(11): 1193–1202. 2006. https://doi.org/10.1016/j.chembiol.2006.09.011

Cherhan C.N. Novel lipid mediators and resolution mechanism in acute inflammation. Am. J. Pathol. 177: 1576–1591. 2010. https://doi.org/10.2353/ajpath.2010.100322

Куликов В.А., Гребенников И.Н. Резольвины, протектины и марезины– новые медиаторы воспаления. Вестник ВГМУ. 11(1): 25–30. 2012. [Kulikov V.A., Grebennikov I.N. Resolvins, protectins and maresins-new inflammatory mediators. Bull. VSMU. 11(1): 25 – 30. 2012. (In Russ)].

Сорокин А.В., Лазаренко В.А., Прибылов С.А. Омега-3 полиненасыщенные жирные кислоты и аспирин как источники нового класса биологически активных веществ: теория и практика. Курский научно-практ. вестник «Человек и его здоровье». 3: 114–122. 2013. [Sorokin A.V., Lazarenko V.A., Pribylov S.A. Omega-3 polyunsaturated fatty acids and aspirin as sources of a new class of biologically active substances: theory and practice. Kursk. Scient. and Pract. Bull. "Man and his health". 3: 114–122. 2013. (In Russ)].

Merched A.J., Ko K., Gotlinger K.H., Serhan C.N., Chan L. Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB. 22(10): 3595–3606. 2008. https://doi.org/10.1096/fj.08-112201

Patrono C., Coller B., Dalen J.E., Hirsh J., Roth G. Platelet-active drugs: the relationships among dose, effectiveness, and side effects. Chest. 119(1): 39–63. 2001. https://doi.org/10.1378/chest.119.1_suppl.39s

Clarke R.J., Mayo G., Price P., FitzGerald G.A. Suppression of thromboxane A2 but not systemic prostacyclin by controlled–release aspirin. N. Engl. J. Med. 325: 1137–1141. 1991. https://doi.org/10.1056/NEJM199110173251605

Mc Adam B.F., Catella–Lawson F., Mardini IA, Kapoor S., Lawson J.A., FitzGerald G.A. Systemic biosynthesis of prostacyclin by cyclooxygenase–2: the human pharmacology of a selective inhibitor of cyclooxygenase–2. Proc. Natl. Acad. Sci. USA. 96(10): 272–277. 1999. https://doi.org/10.1073/pnas.96.1.272

Nagelschmitz J., Blunck M., Kraetzschmar J., Ludwig M., Wensing G., Hohlfeld T. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin. Pharmacol.: Advances and Applications. 6: 51–59. 2014. https://doi.org/10.2147/CPAA.S47895

Fiore L.D. Brophy M.T., Lopez A., Janson P., Deykin D. The bleeding time response to aspirin: identifying the hyperresponder. Am. J. Clin. Pathol. 94(3): 292–296. 1990. https://doi.org/10.1093/ajcp/94.3.292

Bhatt D.L., Topol E.J. Scientific and Therapeutic Advances in Antiplatelet Therapy. Nature Rev. Drug Discovery. 2: 15–28. 2003. https://doi.org/10.1038/nrd985

Alexander J.H., Harrington J.H., Harrington R.A., Tuttle R.H., Berdan L.G., Lincoff A.M., Deckers J.W., Simoons M.L., Guerci A., Hochman J.S., Wilcox R.G., Kitt M.M., Eisenberg P.R., Califf R.M., Topol E.J., Karsh K., Ruzyllo W., Stepinska J., Widimsky P., Boland J.B., Armstrong P.W. Prior aspirin use predicts worse outcomes in patients with non-ST- elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy. Am. J. Cardiol. 83(8): 1147–1151. 1999. https://doi.org/10.1016/s0002-9149(99)00049-1

Gum P.A., Kottke-Marchant K., Poggio E.D., Gurm H., Welsh P.A., Brooks L., Sapp S.K., Topol E.J. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am. J. Cardiol. 88(3): 230–235. 2001. https://doi.org/10.1016/s0002-9149(01)01631-9

Moshfegh K., Redondo M., Julmy F., Wuillemin W.A., Gebauer M.U., Haeberli A., Meyer B.J. Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J. Am. Coll. Cardiol. 36: 699–705. 2000. https://doi.org/10.1016/s0735-1097(00)00817-2

Yusuf S., Zhao F., Mehta S.R., Chrolavicius S., Tognoni G., Fox K.K. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 345(7): 494–502. 2001. https://doi.org/10.1056/NEJMoa010746

Steinhubl S.R., Berger P.B., Mann J.T., Fry E.T., DeLago A., Wilmer C., Topol E.J., CREDO Investigators. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 288(19): 2411–2420. 2002. https://doi.org/10.1001/jama.288.19.2411

Кулаков В.В., Хохлунов С.М. Двойная антитромбоцитарная терапия: современные представления по назначению, прерыванию и возобновлению. Изв. Самарск. научн. центра Рос. акад. наук. 17(2): 331–336. 2015. [KulakovV.V., Khokhlunov S.M. Double antiplatelet therapy: current views on prescription, interruption and resumption. Proc. Samara Scient. Center of the Rus. Acad. Sci. 17(2): 331–336. 2015. (In Russ)].

Valgimigli M., Bueno H., Byrne R.A., Collet J.P., Costa F., Jeppsson A., Jüni P., Kastrati A., Kolh P., Mauri L., Montalescot G., Neumann F.J., Petricevic M., Roffi M., Steg P.G., Windecker S., Zamorano J.L., Levine G.N., ESC Scientific Document Group, ESC Committee for Practice Guidelines (CPG), ESC National Cardiac Societies. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur. Heart J. 39(3): 213–254. 2018. https://doi.org/10.1093/eurheartj/ehx419

Iacoviello L., Curtis A., D'Adamo M.C. Prostacyclin is required for t-PA release after venous occlusion. Am. J. Physiol. Heart and Circul. Physiol. 266(2): 429–434. 1994. https://doi.org/10.1152/ajpheart.1994.266.2.H429

De La Cruz J.P., Guerrero A., Gonzalez-Correa J.A., Arrebola M.M., de la Cuesta S.F. Antioxidant Effect of Acetylsalicylic and Salicylic Acid in Rat Brain Slices Subjected to Hypoxia. J. Neurosci. Res. 75(2): 280–290. 2004. https://doi.org/10.1002/jnr.10851

Korkmaz S., Atmanli A., Li S., Radovits T., Hegedűs P., Barnucz E., Hirschberg K., Loganathan S., Yoshikawa Y., Yasui H., Karck M., Szabó G. Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction. Exp. Biol. Med. (Maywood). 240(9): 1247–1255. 2015. https://doi.org/10.1177/1535370215570184

Sea K., Sohn S.H., Durazo A., Sheng Y., Shaw B.F., Cao X., Taylor A.B., Whitson L.J., Holloway S.P., Hart P.J., Cabelli D.E., Gralla E.B., Valentine J.S. Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase. J. Biol. Chemi. 290(4): 2405 – 2418. 2015. https://doi.org/10.1074/jbc.M114.588798

De Boer M.W., Le Blanc S.J., Dubuc J., Meier S, Heuwieser W, Arlt S, Gilbert R.O., McDougall S. Invited review: Systematic review of diagnostic tests for reproductive-tract infection and inflammation in dairy cows. J. Dairy Sci. 97(7): 3983–3999. 2014. http://dx.doi.org/ 10.3168/jds.2013-7450

Christianson D.W. Structural chemistry and biology of manganese metalloenzymes. Progress Biophys. Mol. Biol. 67(2-3): 217–252. 1997. https://doi.org/10.1016/s0079-6107(97)88477-5

Lindskog S. Cobalt (II) in metalloenzymes. A reporter of structure-function relations. Biochemistry. Berlin, Heidelberg. Springer. 153–196. 1970.

Mc Call K.A., Huang C., Fierke C.A. Function and mechanism of zinc metalloenzymes. J. Nutrition. 130(5S): 1437–1446. 2000. https://doi.org/10.1093/jn/130.5.1437S

Foye W.O., Baum M.D., Williams D.A. Stability of metal complexes of salicylic acid derivatives and analogs III. 3, 6‐dialkyl derivatives and pyridine analogs. J. Pharm. Sci. 56(3): 332 – 336. 1967.

Grisolia S., Mendelson J., Diederich D. Inactivation of metalloenzymes by salicylate. FEBS letters. 11(2): 140–143.1970. https://doi.org/10.1016/0014-5793(70)80512-9

Belhassena I., Nouari W., Messaoud A., Nouar M., Brahimi M., Lamara S.C., Aribi M. Aspirin enhances regulatory functional activities of monocytes and downregulates CD16 and CD40 expression in myocardial infarction autoinflammatory disease. Internat. Immunopharmacol. 83: 106349. 2020. https://doi.org/10.1016/j.intimp.2020.106349

De Meersman R.E., Zion A.S., Lieberman J.S., Downey J.S. Acetylsalicylic acid and autonomic modulation. Clin. Autonomic Res. 10(4): 197–201. 2000. https://doi.org/10.1007/BF02291356

Siepmann M., Rauh R., Spanos E., Dill O., Mueck H., Mueck-Weymann M. The effects of acetylic salicylic acid on heart rate variability in healthy subjects. Clin. Autonomic Res. 17(2): 115–117. 2007. https://doi.org/10.1007/s10286-007-0408-1

Furuno T., Yamasaki F., Yokoyama T., Sato K., Sato T., Doi Y., Sugiura T. Effects of various doses of aspirin on platelet activity and endothelial function. Heart and Vessels. 26(3): 267–273. 2011. https://doi.org/10.1007/s00380-010-0054-8

Yasumasu T., Takahara K., Otsuji Y. Low-dose Aspirin Inhibits Cardiac Sympathetic Activation and Vagal Withdrawal Response to Morning Rising. J. Cardiovasc. Pharmacol. 70(4): 239–244. 2017. https://doi.org/10.1097/FJC.0000000000000509

Ravaeva M.Yu., Chuyan E.N., Cheretaev I.V. Coordinating metal Co2+ and Zn2+ compounds with acetylsalicylic acid: the influence on the cardiorespiratory system. IOP Conference Series: Materials Science and Engineering. 889(1): 012030. 2020. https://doi.org/10.1088/1757-899X/889/1/012030

Korkmaz-Icöz S., Atmanli A., Radovits T., Li S., Hegedüs P., Ruppert M., Brlecic P., Yoshikawa Y., Yasui H., Karck M., Szabó G. Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes. J. Physiol. Sci. 66(2): 113–125. 2016. https://doi.org/10.1007/s12576-015-0403-6

Böger R.H., Bode‐Böger S.M., Kramme P., Tsikas D., Gutzki F.M., Frölich J.C. Effect of captopril on prostacyclin and nitric oxide formation in healthy human subjects: interaction with low dose acetylsalicylic acid. Br. J. Clin. Pharmacol. 42(6): 721–727. 1996. https://doi.org/10.1046/j.1365-2125.1996.00480.x

Hermida R.C., Fernández J.R., Ayala D.E., Mojón A., Iglesias M. Influence of aspirin usage on blood pressure: dose and administration-time dependencies. Chronobiol. Internat. 14(6): 619–637. 1997. https://doi.org/10.3109/07420529709001452

Сонин Д.Л., Дементьева Д.Л., Чефу С.Г. Влияние препарата Нотромбел на системную гемодинамику и толерантность к тромбину в эксперименте. Регионарн. кровообращение и микроциркуляция. 16(4): 65–72. 2017. [Sonin D.L., Dementieva D.L., Chefu S.G. Effect of the drug Notrombel on systemic hemodynamics and thrombin tolerance in the experiment. Regional blood circulation and microcirculation. 16(4): 65–72. 2017. (In Russ)]. https://doi.org/10.24884/1682-6655-2017-16-4-65-72

Leithäuser B., Mrowietz C., Park J.W., Jung F. Influence of acetylsalicylic acid (Aspirin) on cutaneous microcirculation. Clin. Hemorheol. Microcirculat. 50(1-2): 25–34. 2012. https://doi.org/10.3233/CH-2011-1440

Buchanec J., Visnovský P., Buchancová J., Cervenáková E. The effect of acetylsalicylic acid on some parameters of peripheral circulation in children (author's transl). Klin. Pediatrie. 191(3): 301–304. 1979.

Dahmus J.D., Bruning R.S., Larry K.W., Alexander L.M. Oral clopidogrel improves cutaneous microvascular function through EDHF-dependent mechanisms in middle-aged humans. Am. J. Physiol. Regulatory, Integrative and Compar. Physiol. 305(4): 452–458. 2013. https://doi.org/10.1152/ajpregu.00366.2012

Holowatz L.A., Jennings J.D., Lang J.A., Kenney W.L. Systemic low-dose aspirin and clopidogrel independently attenuate reflex cutaneous vasodilation in middle-aged humans. J. Appl. Physiol. 108(6): 1575–1581. 2010. https://doi.org/10.1152/japplphysiol.01362.2009

Bulckaen H., Prévost G., Boulanger E., Robitaille G., Roquet V., Gaxatte C., Garçon G., Corman B., Gosset P., Shirali P., Creusy C., Puisieux F. Low-dose aspirin prevents age-related endothelial dysfunction in a mouse model of physiological aging. Am. J. Physiol. Heart Circ. Physiol. 294(4): H1562 – H1570. 2008. https://doi.org/10.1152/ajpheart.00241.2007

Mikhailichenko L.A., Tikhomirova I.A. Parameters of microcirculation in paired formations after single aspirin administration: laser Doppler flowmetry data. Bull. Exp. Biol. Med. 151(1): 16–21. 2011. https://doi.org/ 10.1007/s10517-011-1249-4

Раваева М.Ю., Чуян Е.Н., Миронюк И.С., Черетаев И.В., Гришина Т.В. Показатели тканевой микрогемодинамики крыс при действии ацетилсалициловой кислоты и ее комплексных соединений с металлами. Журн. эвол. биох. физиол. 57(1): 71–82. 2021. [Ravaeva M.Yu., Chuyan E.N., Mironyuk I.S., Cheretaev I.V., Grishina T.V. Indicators of tissue microhemodynamics in rats exposed to acetylsalicylic acid and metal salicylates. J. Evol. Biohim. Phys. 57(1): 71–82. 2021. (In Russ)]. https://doi.org/10.31857/S0044452921010083