The use of L-lysine aescinate in patients with novel coronavirus infection and acute cerebrovascular accident

DOI: https://doi.org/10.29296/25877305-2023-01-17
Issue: 
1
Year: 
2023

Associate Professor E. Tokareva(1, 2), Candidate of Medical Sciences; V. Gorbunov(3)
1-N.I. Pirogov Sevastopol City Hospital One
2-S.I. Georgievsky Medical Academy, V.I. Vernadsky Crimean Federal University, Simferopol
3-OOO “Art Farm”, Moscow

The paper presents the results of a study of the effect of L-lysine aescinate on the time course of changes in the clinical and laboratory parameters of patients with acute cerebrovascular accident in the presence of the novel coronavirus infection. L-lysine aescinate enhances the efficiency of the basic therapy, which is confirmed by more pronounced changes in the number of laboratory parameters, including coagulograms, inflammatory markers, and predictors for cardiovascular catastrophes, as well as by an improvement in neurological recovery. The study shows that L-lysine aescinate is well tolerated and there are no adverse reactions. A rationale is provided for the necessity of incorporating L-lysine aescinate in the treatment regimen as an angioprotective, decongestant, and neuroprotective agent.

Keywords: 
neurology
infectious diseases
acute cerebrovascular accidents
novel coronavirus infection (COVID-19)
ischemic stroke
hemorrhagic stroke
L-lysine aescinate.



References: 
  1. Mao L., Jin H., Wang M. et al. Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77 (6): 683–90. DOI: 10.1001/jamaneurol.2020.1127
  2. McNamara D. COVID-19 Linked to Large Vessel Stroke in Young Adults. Medscape Medical News. April 24, 2020. URL: https://www.medscape.com/viewarticle/929345?src=wnl_edit_tpal&uac=296430PX&impID=2359734&faf=1
  3. Грей А.Дж., Баггл Ф., Бехер Х. и др. Недавняя бактериальная и вирусная инфекция является фактором риска цереброваскулярной ишемии: клинические и биохимические исследования. Неврология. 1998; 50 (1): 196–203 [Grei A.Dzh., Baggl F., Bekher Kh. et al. Nedavnyaya bakterial'naya i virusnaya infektsiya yavlyaetsya faktorom riska tserebrovaskulyarnoi ishemii: klinicheskie i biokhimicheskie issledovaniya. Nevrologiya. 1998; 50 (1): 196–203 (in Russ.)].
  4. Li Y., Li M., Wang M. et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020; 5 (3): 279–84. DOI: 10.1136/svn-2020-000431
  5. Путилина М.В., Вечорко В.И., Гришин Д.В. и др. Острые нарушения мозгового кровообращения, ассоциированные с короновирусной инфекцией SARS-CoV-2 (COVID-19). Журнал неврологии и психиатрии им. С.С. Корсакова. 2020; 120 (12): 109–17 [Putilina M.V., Vechorko V.I., Grishin D.V. et al. Acute cerebrovascular accidents associated with SARS-CoV-2 coronavirus infection (COVID-19). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2020; 120 (12): 109–17 (in Russ.)]. DOI: 10.17116/jnevro2020120121109
  6. Sorice M., Misasi R., Riitano G. et al. (2021). Targeting Lipid Rafts as a Strategy Against Coronavirus. Front Cell Dev Biol. 2021; 8: 618296. DOI: 10.3389/fcell.2020.618296
  7. Sviridov D., Miller Y.I., Ballout R.A. et al. Targeting Lipid Rafts – A Potential Therapy for COVID-19. Front Immunol. 2020; 11: 574508. DOI: 10.3389/fimmu.2020.574508
  8. Böttger S., Melzig M.F. The influence of saponins on cell membrane cholesterol. Bioorg Med Chem. 2013; 21 (22): 7118–24. DOI: 10.1016/j.bmc.2013.09.008
  9. Sun M., Northup N., Marga F. et al. The effect of cellular cholesterol on membrane-cytoskeleton adhesion. J Cell Sci. 2007; 120: 2223–31. DOI: 10.1242/jcs.001370
  10. Qiao J., Xu L.H., He J. et al. Cucurbitacin E exhibits anti-inflammatory effect in RAW 264.7 cells via suppression of NF-kappaB nuclear translocation. Inflamm Res. 2013; 62 (5): 461–9. DOI: 10.1007/s00011-013-0598-z
  11. Kim J.Y., Lee Y.G., Kim M.Y. et al. Src-mediated regulation of inflammatory responses by actin polymerization. Biochem Pharmacol. 2010; 79 (3): 431–43. DOI: 10.1016/j.bcp.2009.09.016
  12. Zeng C., Morrison A.R. Disruption of the actin cytoskeleton regulates cytokine-induced iNOS expression. Am J Physiol Cell Physiol. 2001; 281 (3): C932–40. DOI: 10.1152/ajpcell.2001.281.3.C932
  13. Domanski D., Zegrocka-Stendel O., Perzanowska A. et al. Molecular Mechanism for Cellular Response to β-Escin and Its Therapeutic Implications. PLoS One. 2016; 11 (10): e0164365. DOI: 10.1371/journal.pone.0164365
  14. Федин А.И., Дьяконова Е.Н., Макерова В.В. и др. Применение L-лизина эсцината в лечении венозной энцефалопатии. Невроньюс. 2015; 12: 3–4 [Fedin A.I., D'yakonova E.N., Makerova V.V. et al. Primenenie L-lizina estsinata v lechenii venoznoi entsefalopatii. Nevron'yus. 2015; 12: 3–4 (in Russ.)].
  15. Дьяконова Е.Н., Макерова В.В. Эффективная терапия вегетососудистой дистонии у пациентов молодого возраста. Лечащий врач. 2016; 2: 17–23 [Dyakonova E.N., Makerova V.V. Effective therapy vascular dystonia in young patients. Lechashchii vrach. 2016; 2: 17–23 (in Russ.)].
  16. Sirtori K.R. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Chem Farm Bull (Tokyo). 2001; 49 (5): 626–8. DOI: 10.1006/phrs.2001.0847
  17. Дьяконова Е.Н., Макерова В.В., Ковалева Т.Э. Особенности микроциркуляции у пациентов молодого возраста с вегетососудистой дистонией. Мат-лы 4 междунар. научно-практ. конф. Scientific achievements of the third millennium (IV International Scientific Conference), LJournal, Los Angeles, 2016 [Dyakonova E.N., Makerova V.V., Kovaleva Т.E. Features of microcirculation in patients of young age with vascular dystonia. Materials of the IV International Scientific Conference «Scientific achievements of the third millennium» (IV International Scientific Conference). Los Angeles: LJournal; 2016 (in Russ.)]. DOI: 10.18411/scc-15-10-2016-04
  18. Дьяконова Е.Н, Федин А.И., Макерова В.В. и др. L-лизина эсцинат в лечении микроциркуляторных расстройств при нарушении интракраниального венозного оттока у пациентов с синдромом вегетативной дистонии. Журнал неврологии и психиатрии им. С.С. Корсакова. 2016; 116 (9): 42–50 [Dyakonova E.N., Fedin A.I., Makerova V.V. et al. The use of L-lysine aescinat in the treatment of microcirculatory disturbances in patients young and middle age with violation of the intracranial venous outflow. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2016; 116 (9): 42–50 (in Russ.)]. DOI: 10.17116/jnevro20161169142-50
  19. Janet G. Chronic venous insufficiency: worldwide results of the RELIEF study. Assessment of reflux and improvement of quality of life with the help of micronized flavonoids. Angiology. 2002; 53 (3): 245–56. DOI: 10.1007/s11255-011-0038-3
  20. Tang N., Li D., Wang X. et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18: 844–7. DOI: 10.1111/jth.14768
  21. Fuchs N.A., Brill A., Wagner D.D. Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis. Arterioscler Thromb Vasc Biol. 2012; 32 (8): 1777–83. DOI: 10.1161/ATVBAHA.111.242859
  22. Seal J.B., Gewertz B.L. Vascular dysfunction in ischemia-reperfusion injury. Ann Vasc Surg. 2005; 19 (4): 572–84. DOI: 10.1007/s10016-005-4616-7
  23. Ward B.J., Donnelly J.L. Hypoxia induced disruption of the cardiac endothelial glycocalyx: implications for capillary permeability. Cardiovasc Res. 1993; 27 (3): 384–9. DOI: 10.1093/cvr/27.3.384
  24. Mulivor A.W., Lipowsky H.H. Inflammation- and ischemia-induced shedding of venular glycocalyx. Am J Physiol Heart Circ Physiol. 2004; 286 (5): H1672–80. DOI: 10.1152/ajpheart.00832.2003
  25. Habazettl H., Kupatt C., Zahler S. et al. Selectins and beta 2-integrins mediate post-ischaemic venular adhesion of polymorphonuclear leukocytes, but not capillary plugging, in isolated hearts. Pflugers Arch. 1999; 438 (4): 479–85. DOI: 10.1007/s004249900063
  26. Chappell D., Jacob M., Hofmann-Kiefer K. et al. Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion. Cardiovasc Res. 2009; 83 (2): 388–96. DOI: 10.1093/cvr/cvp097
  27. Bruegger D., Rehm M., Jacob M. et al. Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts. Crit Care. 2008; 12 (3): R73. DOI: 10.1186/cc6913
  28. Chappell D., Jacob M., Hofmann-Kiefer K. et al. Hydrocortisone preserves the vascular barrier by protecting the endothelial glycocalyx. Anesthesiology. 2007; 107: 776–84. DOI: 10.1097/01.anes.0000286984.39328.96
  29. Schouten M., Wiersinga W.J., Levi M. et al. Inflammation, endothelium, and coagulation in sepsis. J Leukoc Biol. 2008; 83 (3): 536–45. DOI: 10.1189/jlb.0607373
  30. Becker B.F., Heindl B., Kupatt C. et al. Endothelial function and hemostasis. Z Kardiol. 2000; 89 (3): 160–7. DOI: 10.1007/pl00007320
  31. Mochizuki S., Vink H., Hiramatsu O. et al. Role of hyaluronic acid in shear induced endothelium derived nitric oxide release. Am J Physiol Heart Circ Physiol. 2003; 285 (2): H722–6. DOI: 10.1152/ajpheart.00691.2002
  32. Florian J.A., Kosky J.R., Ainslie K. et al. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ Res. 2003; 93 (10): e136–42. DOI: 10.1161/01.RES.0000101744.47866.D5
  33. Thi M.M., Tarbell J.M., Weinbaum S. et al. The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: a bumper-car model. Proc Natl Acad Sci USA. 2004; 101 (47): 16483–8. DOI: 10.1073/pnas.0407474101
  34. Pohl U., De Wit C., Gloe T. Large arterioles in the control of blood flow: role of endothelium-dependent dilation. Acta Physiol Scand. 2000; 168 (4): 505–10. DOI: 10.1046/j.1365-201x.2000.00702.x
  35. Владимиров Ю.А. Биологические мембраны и незапрограммированная смерть клетки. Соросовский образовательный журнал. 2000; 6 (9): 2–9 [Vladimirov Yu.A. Biological membranes and non-programmed cell death. Sorosovskii obrazovatel'nyi zhurnal. 2000; 6 (9): 2–9 (in Russ.)].
  36. Vink H., Constantinescu A.A., Spaan J.A. Oxidized lipoproteins degrade the endothelial surface layer: implications for platelet-endothelial cell adhesion. Circulation. 2000; 101 (13): 1500–2. DOI: 10.1161/01.cir.101.13.1500
  37. Czarnowska E., Karwatowska-Prokopczuk E. Ultrastructural demonstration of endothelial glycocalyx disruption in the reperfused rat heart. Involvement of oxygen free radicals. Basic Res Cardiol. 1995; 90 (5): 357–64. DOI: 10.1007/BF00788496
  38. Becker B.F., Chappell D., Bruegger D. et al. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc Res. 2010; 87 (2): 300–10. DOI: 10.1093/cvr/cvq137
  39. Rubio-Gayosso I., Platts S.H., Duling B.R. Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2006; 290 (6): H2247–56. DOI: 10.1152/ajpheart.00796.2005
  40. Meng J., Xiao G., Zhang J. et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020; 9 (1): 757–60. DOI: 10.1080/22221751.2020.1746200
  41. Громова О.А., Торшин И.Ю., Путилина М.В. и др. Выбор схем нейропротекторной терапии у пациентов с хронической ишемией головного мозга с учетом синергизма лекарственных взаимодействий. Журнал неврологии и психологии им. С.С. Корсакова. 2020; 120 (8): 42–50 [Gromova O.A., Torshin I.Yu., Putilina M.V. et al. Choice of neuroprotective therapy regimens in patients with chronic cerebral ischemia, taking into account the synergy of drug interactions. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2020; 120 (8): 42–50 (in Russ.)]. DOI: 10.17116/jnevro202012008142