Blood coagulation system in experimental acute lung injury and its treatment with dexamethasone

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Abstract

The effects of short- and long-term administrations of dexamethasone on survival, severity of pulmonary edema, and hemostasis on experimental lipopolysaccharide-induced acute lung injury in rats were analyzed. Acute lung injury in rats was modeled by the intratracheal injection of lipopolysaccharide from the Salmonella enterica cell wall. White male rats were randomly divided into nine groups: the intact group consisted of 10 animals; two control groups of 20 animals each, in which acute lung injury was simulated without further treatment and removed from the experiment on day 3 or 7; six comparison groups of 20 animals each, in which, 3 h after modeling of acute lung injury and then once a day for 3 days (short mode of administration) or 7 days (long mode of administration), dexamethasone solution was administered intraperitoneally in the following doses: 0. 52 (equivalent to 6 mg/day for humans), 1. 71 (20 mg/day for humans), and 8 mg/kg/day (94 mg/day, pulse therapy for humans). On days 3 and 7, the survival rate, coagulogram values (active partial thromboplastin time, prothrombin time, activity of antithrombin, and soluble fibrin monomer complexes), and low-frequency piezotromboelastography data were assessed in the surviving animals. The results revealed that dexamethasone reduces mortality in acute lung injury and has a dose-dependent effect on the hemostasis system: with an increase in the dose administered, blood clotting processes increase and fibrinolysis is inhibited. Low-frequency piezothromboelastography with a conventional coagulogram allows for a comprehensive assessment of the hemostasis system, identifying violations, and timely drug correction.

About the authors

Nikita I. Voloshin

Kirov Military Medical Academy

Author for correspondence.
Email: nikitavoloshin1990@gmail.com
ORCID iD: 0000-0002-3880-9548
SPIN-code: 6061-4342
Scopus Author ID: 57926549500
ResearcherId: HSG-7925-2023

adjunct

Russian Federation, Saint Petersburg

Evgeny O. Chuchalin

Kirov Military Medical Academy

Email: cheuspb@gmail.com
ORCID iD: 0000-0002-4162-910X
SPIN-code: 7584-4729
ResearcherId: GZA-7499-2022

cadet

Russian Federation, Saint Petersburg

Victoria A. Pugach

State Scientific Research Testing Institute of Military Medicine

Email: gniiivm_7@mil.ru
ORCID iD: 0000-0003-4290-350X
SPIN-code: 3739-3699
Scopus Author ID: 57195201128
ResearcherId: ACD-0418-2022

MD, Cand. Sci. (Biol. ), senior research associate

Russian Federation, Saint Petersburg

Vladimir V. Salukhov

Kirov Military Medical Academy

Email: vlasaluk@yandex.ru
ORCID iD: 0000-0003-1851-0941
SPIN-code: 4531-6011
Scopus Author ID: 55804184100

MD, Dr. Sci. (Med.), assistant Professor

Russian Federation, Saint Petersburg

Mikhail A. Tyunin

State Scientific Research Testing Institute of Military Medicine

Email: Tuynin84@yandex.ru
ORCID iD: 0000-0002-6974-5583
SPIN-code: 6161-7029
Scopus Author ID: 25032311600

MD, Cand. Sci. (Med.)

Russian Federation, Saint Petersburg

Mikhail A. Kharitonov

Kirov Military Medical Academy

Email: micjul11@yandex.ru
ORCID iD: 0000-0002-6521-7986
SPIN-code: 7678-2278
Scopus Author ID: 57521284600
ResearcherId: H-6056-2015

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Yuri V. Rudakov

Kirov Military Medical Academy

Email: rudakov_yura@mail.ru
ORCID iD: 0000-0001-7914-6173
SPIN-code: 5864-3853

MD, Cand. Sci. (Med.), assistant Professor

Russian Federation, Saint Petersburg

Alexey A. Minakov

Kirov Military Medical Academy

Email: minakom@mai.ru
ORCID iD: 0000-0003-1525-3601
SPIN-code: 5344-7883
Scopus Author ID: 57926549400
ResearcherId: HSG-9445-2023

adjunct

Russian Federation, Saint Petersburg

Yuriy B. Goverdovskiy

Kirov Military Medical Academy

Email: goverdoc@yandex.ru
ORCID iD: 0000-0003-1241-9725
SPIN-code: 2605-7097

MD, Dr. Sci. (Med.), Professor

Russian Federation, Saint Petersburg

Tatyana A. Belyakova

Kirov Military Medical Academy

Email: tanyarus69@mail.ru
ORCID iD: 0009-0004-6005-733X
SPIN-code: 8863-6596
ResearcherId: ISB-1403-2023

cadet

Saint Petersburg

Viktoriya V. Kochukova

Kirov Military Medical Academy

Email: kochukova.vika@mail.ru
SPIN-code: 6263-3600
ResearcherId: ISB-2732-2023

cadet

Russian Federation, Saint Petersburg

References

  1. Ivchenko EV, Kotiv BN, Ovchinnikov DV, et al. Results of the work of the Military medical academy research institute of novel coronavirus infection problems through 2020–2021. Bulletin of the Russian Military Medical Academy. 2021;23(4):93–104. (In Russ.). doi: 10.17816/brmma83094
  2. Andreenko AA, Andreichuk YuV, Arsent’ev VG, et al. Infektsiya, vyzvannaya SARS-COV-2. Kryukova EV, ed. Saint Petersburg. 2023. 260 p. (In Russ.).
  3. Bucenko SA, Sergoventsev AA, Kuznetsova RY, et al. Factors contributing to the new coronavirus infection, increased risk of complications and death from it in the armed forces of the Russian Federation. Bulletin of the Russian Military Medical Academy. 2023;25(1):121–132. (In Russ.). doi: 10.17816/brmma112377
  4. Salukhov VV, Kharitonov MA, Kryukov EV, et al. Topical issues of diagnostics, examination and treatment of patients with COVID-19-associated pneumonia in different countries and continents. Medical Council. 2020;21:96–102. (In Russ.). doi: 10.21518/2079-701X-2020-21-96-102
  5. Makarova EV, Tyurikova LV, Lyubavina NA. The use of systemic corticosteroids in a new coronavirus infection (from the standpoint of international and Russian recommendations. Medical Almanac. 2021;1(66):74–82. (In Russ.).
  6. Opal SM. Phylogenetic and functional relationships between coagulation and the innate immune response. Crit Care Med. 2000;28(9):S77–S80. doi: 10.1097/00003246-200009001-00017
  7. Chapman HA. Plasminogen activators, integrins, and the coordinated regulation of cell adhesion and migration. Curr Opin Cell Biol. 1997;9(5):714–724. doi: 10.1016/s0955-0674(97)80126-3
  8. Miller DL. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide. Am J Respir Cell Mol Biol. 2002;26(6):650–658. doi: 10.1165/ajrcmb.26.6.4688
  9. Okajima K. Antithrombin prevents endotoxin-induced pulmonary vascular injury by inhibiting leukocyte activation. Blood Coagul Fibrinolysis.1998;9:S25–S37.
  10. Idell S. Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways. Crit Care Med. 2002;30(5): S274–S280. doi: 10.1097/00003246-200205001-00017
  11. Morange PE, Aubert J, Peiretti F, et al. Glucocorticoids and insulin promote plasminogen activator inhibitor 1 production by human adipose tissue. Diabetes. 1999;48(4):890–895. doi: 10.2337/diabetes.48.4.890
  12. Yaroshetskiy AI, Gritsan AI, Avdeev SN, et. al. Diagnostics and intensive therapy of acute respiratory distress syndrome (clinical guidelines of the federation of anesthesiologists and reanimatologists of Russia). Russian Journal of Anаеsthesiology and Reanimatology. 2020;(2):5–39. (In Russ.). doi: 10.17116/anaesthesiology20200215
  13. Fan E, Del Sorbo L, Goligher EC, et al. American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017;195(9):1253–1263. doi: 10.1164/rccm.201703-0548ST
  14. Majoor CJ, Sneeboer MM, de Kievit A, et al. The influence of corticosteroids on hemostasis in healthy subjects. J Thromb Haemost. 2016;14(4):716–723. doi: 10.1111/jth.13265
  15. Heaton JH, Nebes VL, O’Dell LG, et al. Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocyte. Mol Endocrinol. 1989;3(1):185–192. doi: 10.1210/mend-3-1-185
  16. Stolz E, Klötzsch C, Schlachetzki F, et al. High-dose corticosteroid treatment is associated with an increased risk of developing cerebral venous thrombosis. Eur Neurol. 2003;49(4):24–78. doi: 10.1159/000070197
  17. Edalatifard M, Akhtari M, Salehi M, et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020;56(6):2002808. doi: 10.1183/13993003.02808-2020
  18. Munch MW, Myatra SN, Vijayaraghavan B, et al. Effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support in adults with COVID-19 and severe hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021;326(18):1807–1817. doi: 10.1001/jama.2021.18295
  19. Majoor CJ, Sneeboer MM, de Kievit A, et al. The influence of corticosteroids on hemostasis in healthy subjects. J Thromb Haemost. 2016;14(4):716–723. doi: 10.1111/jth.13265
  20. Maxwell M, Moots S, Kendall R. Corticosteroids: Do they damage the cardiovascular system? Postgrad Med J. 1995;70(830):863–870. doi: 10.1136/pgmj.70.830.863
  21. Matute-Bello G, Downey G, Moore BB, et al. Acute Lung Injury in Animals Study Group. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44(5):725–738. doi: 10.1165/rcmb.2009-0210ST
  22. Pugach VA, Strokina EI, Isaeva AA, et al. Pokazateli plazmennogo gemostaza v eksperimental’noi modeli ostrogo respiratornogo distress-sindroma Aktual’nye problemy biomeditsiny In: Collection of abstracts of the XXVI All-Russian Conference of Young Scientists with International participation “Aktual’nye problemy biomeditsiny”. Saint Petersburg; 2020. P. 152–154. (In Russ.).
  23. Salukhov VV, Voloshin NI, Shperling MI. Effectiveness of various regimens of systemic anti-inflammatory therapy with glucocorticoids in the development of acute LPS-induced lung damage in the experiment. Russian Military Medical Academy Reports. 2022;41(2):111–116. (In Russ.). doi: 10.17816/rmmar104619
  24. European Convention for the Protection of Vertebrate Animals used for Experimental or other Scientific Purposes. Introduction 03.18.1986. Strasburg, 1986. 13 p.
  25. Directive of the European Parliament and of the Council of the European Union on the protection of animals used for scientific purposes (complies with the requirements of the European Economic Area) № 2010/63/eu. Intr. 01.01.2013. Strasbourg, 2010. 48 p.
  26. Shekunova EV, Kovaleva MA, Makarova MN, et al. The choice of dose of the drug for preclinical studies: interspecies transfer of doses. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya. 2020;10(1):19–28 (In Russ.). doi: 10.30895/1991-2919-2020-10-1-19-28

Supplementary files

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2. Fig. 1. Design of the experiment

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3. Fig. 2. Survival curves after modeling of acute lung injury and treatment with dexamethasone in various regimens: *Differences relative to the control group, p < 0. 05

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4. Fig. 3. Mass coefficient of the lungs in rats on days 3 and 7 after the modeling of acute lung injury and treatment with dexamethasone in various regimens, Me [Q1; Q3]:*differences relative to the control group; # relative to the group of intact animals, p < 0. 05

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