Опубликовать статью

Информационное партнерство

Инфоресурсы

Контакты

«

Vol. 24, Art. 53 (pp. 715-728)    |    2023       

»

Experimental study of the therapeutic efficacy of anticoagulants and endothelioprotectors on a model of acute respiratory distress-syndrome

Pugach V.A., Tyunin M.A., Ilinskiy N.S., Levchuk E.V., Zalyalov M.N., Izhorskaya E.Yu.

State Scientific Research Testing Institute of Military Medicine

Brief summary

to experimentally investigate the therapeutic efficacy of anticoagulants and endothelioprotectors when used as part of the combined pharmacological therapy of acute respiratory distress syndrome (ARDS) in rats. Materials and methods: the work was performed on 220 adult male outbred rats weighing 300-350 g. ARDS was modeled by a single intratracheal injection of Salmonella enterica lipopolysaccharide (LPS) at a dose of 20 mg/kg. The experimental work was carried out in 2 stages. At the 1st stage the most effective anticoagulants and endothelioprotectors were determined based on the evaluation of hemostasis tests. At the 2nd stage the therapeutic efficacy of the selected drugs in combination with the basic therapy scheme was investigated. Treatment of animals was started 6 hours after administration of LPS, while the duration of therapy at the 1st stage was 2 days, and at the 2nd stage - 7 days. The following anticoagulants were used: heparin sodium (642 U/kg subcutaneously 3 times a day), enoxaparin sodium (6,0 mg/kg subcutaneously 2 times a day), dabigatran etexilate (13,0 mg/kg intragastrically 2 times a day), rivaroxaban (10,0 mg/kg intragastrically 2 times a day). Sulodexide (42,9 U/kg intragastrically 2 times a day) and defibrotide sodium (56,3 mg/kg intraperitoneal 2 times a day) were used as endothelioprotectors. Anticoagulants and endothelioprotectors were used in combination with the basic scheme of therapy: ceftriaxone (50,0 mg/kg intramuscularly 2 times a day), dexamethasone (0,87 mg/kg intramuscularly 2 times a day) and aminophylline (7,0 mg/kg intramuscularly 2 times a day). Results. The combination of enoxaparin sodium and defibrotide sodium had the best therapeutic effect in experimental ARDS. The therapeutic effect of the studied drugs was manifested in a decrease of pulmonary edema severity and respiratory failure. Conclusions. The findings are significant for justification of further studies of the efficacy and safety of the combined use of enoxaparin sodium and defibrotide sodium for the correction of hypercoagulation disorders and endothelial dysfunction in the early stages of ARDS development


Key words

acute respiratory distress syndrome; pulmonotoxicity; lipopolysaccharide; hemostasis; hypercoagulation; endothelial dysfunction; therapy

Reference list

1. Yarosheckii A.I., Grican A.I., Avdeev S.N. i dr. Diagnostika i intensivnaya terapiya ostrogo respiratornogo distress-sindroma. Anesteziologiya i reanimatologiya (Media Sfera). 2020; 2: 5-39. https://doi.org/10.17116/anaesthesiology20200215.


2. Angelini D.J., Dorsey R.M., Willis K.L. et al. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies? Inhal. Toxicol. 2013; 25(1): 37-62. https://doi.org/10.3109/08958378.2012.750406.


3. Basharin V.A., Chepyr S.V., Shegolev A.V. i dr. Rol i mesto respiratornoi podderjki v shemah terapii ostrogo legochnogo oteka, vizvannogo ingalyacionnim vozdeistviem toksichnih veshestv. Voenno-medicinskii jyrnal. 2019; 340(11): 26-32.


4. Huppert L.A., Matthay M.A., Ware L.B. Pathogenesis of Acute Respiratory Distress Syndrome. Semin Respir Crit Care Med. 2019; 40(1): 31-39. https://doi.org/10.1055/s-0039-1683996.


5. Camprubí-Rimblas M., Tantinyà N., Bringué J. et al. Anticoagulant therapy in acute respiratory distress syndrome. Ann. Transl. Med. 2018; 6(2): 36. https://doi.org/10.21037/atm.2018.01.08.


6. Livingstone S.A., Wildi K.S., Dalton H.J. et al. Coagulation Dysfunction in acute respiratory distress syndrome and its potential impact in inflammatory subphenotypes. Frontiers in medicine. 2021; 8: 723217. https://doi.org/10.3389/fmed.2021.723217.


7. Vassiliou A.G., Kotanidou A., Dimopoulou I. et al. Endothelial damage in acute respiratory distress syndrome. International journal of molecular sciences. 2020; 21(22): 8793. https://doi.org/10.3390/ijms21228793.


8. Shekynova E.V., Kovaleva M.A., Makarova M.N., Makarov V.G. Vibor dozi preparata dlya doklinicheskogo issledovaniya: mejvidovoi perenos doz. Vedomosti Naychnogo centra ekspertizi sredstv medicinskogo primeneniya. 2020; 10(1): 19-28. https://doi.org/10.30895/1991-2919-2020-10-1-19-28.


9. Mironov A.N. Rykovodstvo po provedeniu doklinicheskih issledovanii lekarstvennih sredstv. Chast pervaya. M.: Grif i K; 2012. 944 s.


10. Bravo-Pérez C., Vicente V., Corral J. Management of antithrombin deficiency: an update for clinicians. Expert Rev Hematol. 2019; 12(6): 397-405. https://doi.org/10.1080/17474086.2019.1611424.


11. Frame D., Scappaticci G.B., Braun T.M. et al. Defibrotide Therapy for SARS-CoV-2 ARDS. Chest. 2022; 162(2): 346-355. https://doi.org/10.1016/j.chest.2022.03.046.


12. Li J., Li Y., Yang B. et al. Low-molecular-weight heparin treatment for acute lung injury/acute respiratory distress syndrome: a meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2019; 11(2): 414-422.


13. Jiang X., Feng R., Liu J. et al. Meta-analysis of the curative effect of low molecular weight heparin on acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2020; 32(12): 1472-1478. https://doi.org/10.3760/cma.j.cn121430-20201019-01426.