N.I. Voloshin1, Adjunct of the first department and clinic of advanced therapy for doctors, https://orcid.org/0000-0002-3880-9548
V.A. Pugach2*, PhD, Senior Researcher, https://orcid.org/0000-0003-4290-350X
M.A. Tyunin2, PhD, deputy Head of the center, https://orcid.org/0000-0002-6974-5583
E.I. Strokina2, Researcher, https://orcid.org/0000-0003-4162-3135
V.V. Hizha2, Laboratory researcher, https://orcid.org/0000-0003-4967-472X
A.V. Nikolaev1, PhD, Docent of the first department and clinic of advanced therapy for doctors, https://orcid.org/0000-0003-3209-3742
V.V. Salukhov1, Doctor of Medical Sciences, Head of the first department and clinic of advanced therapy for doctors, https://orcid.org/0000-0003-1851-0941
1 S.M. Kirov Military Medical Academy,
194044, Russia, St. Petersburg, 6, Academician Lebedev St.
2 State Scientific Research Testing Institute of Military Medicine,
195043, Russia, St. Petersburg, 4, Lesoparkovaya St.
* E-mail: [email protected]
acute lung injury
acute respiratory distress syndrome
The study was performed without external funding.
Voloshin N.I., Pugach V.A., Tyunin M.A., Strokina E.I., Hizha V.V., Nikolaev A.V., Salukhov V.V. Clinical, biochemical and pathomorphological features of direct acute lung injury in rats caused by intratracheal administration of Salmonella enterica lipopolysaccharide. Laboratory Animals for Science. 2022; 3. https://doi.org/10.29296/2618723X-2022-03-02
The aim of this study was to assess the clinical, biochemical and pathomorphological features of direct acute lung injury (ALI) in rats caused by intratracheal (i/t) administration of Salmonella enterica lipopolysaccharide at a dose of 20 mg/kg (LD50).
The study used 67 outbred male rats aged 8–12 weeks, weighing 310–350 g (Rappolovo’s nursery, Leningrad Region) which were divided into 2 groups according to the method of analogues: experimental and control. The experimental work was carried out in two stages. At the first stage within 4 days after ALI modeling the general condition of animals, body weight and temperature and dynamics of animal death were recorded. In a separate series of experiments we studied the pathomorphological changes in rats lung tissue. At the second stage 3 days after i/t administration of LPS blood was taken from rats for laboratory studies. The indicators of clinical and biochemical blood tests, hemostasiogram, blood gases and electrolytes were studied. In addition the gravimetric parameters of lungs (lung coefficient and moisture saturation) were measured.
The studied model of ALI characterized decreasing body weight in experimental group by an average of 15%, a persistent hypothermia and the development of inflammatory histomorphological changes in the lungs 2–3 days after i/t administration of LPS. The death of animals after ALI was recorded in the period from 12 hours to 3 days. The effective time of death was 29,10±3,05 hours.
According to laboratory studies, leukocytosis, increasing concentration of soluble fibrin-monomer complexes and fibrinogen, hyperkalemia, hypoglycemia, hypoxemia and acidosis were recorded in experimental group on the 3rd day after ALI modeling. These changes in laboratory parameters were detected with an increased lung coefficient and its moisture saturation, which indicated the development of pulmonary edema.
Simplicity of execution, high reproducibility, the presence of typical signs of acute inflammatory lung injury, as well as an available set of laboratory criteria for determining the severity of pathological process allows us to recommend this ALI model for preclinical studies aimed at finding and evaluating the effectiveness of candidate drugs for the prevention and treatment of acute respiratory distress syndrome.
Conflict of interest
The authors declare no conflict of interest.
N.I. Voloshin — conducting experiments, collecting data, analyzing data, writing a manuscript.
V.A. Pugach — conducting experiments, collecting data, analyzing data, writing a manuscript.
E.I. Strokina — experimental modeling, selection of biomaterial.
V.V. Hizha — conducting laboratory research methods.
M.A. Tyunin — critical revision of the manuscript and approval of the final version of the article for publication.
A.V. Nikolaev — development of the concept of the study and a critical review of its content.
V.V. Salukhov — development of the concept of the study and a critical review of its content.
Ярошецкий А.И., Грицан А.И., Авдеев С.Н. и др. Диагностика и интенсивная терапия острого респираторного дистресс-синдрома // Анестезиология и реаниматология. 2020. Т. 2. С. 5–39 [Yaroshetsky A.I., Gritsan A.I., Avdeev S.N. et al. Diagnostics and intensive therapy of Acute Respiratory Distress Syndrome // Russian Journal of Anaesthesiology and Reanimatology. 2020. Vol. 2. P. 5–39 (In Russ.)] https://doi.org/10.17116/anaesthesiology20200215.
Fan E., Del Sorbo L., Goligher E.C. et al. 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. Vol. 195 (9). P. 1253–1263. https://doi.org/10.1164/rccm.201703-0548ST.
Griffiths M.J.D., McAuley D.F., Perkins G.D. et al. Guidelines on the management of acute respiratory distress syndrome // BMJ Open Respiratory Research. 2019. 6: e000420. https://doi.org/10.1136/bmjresp-2019-000420.
Gibson P.G., Qin L., Puah S.H. COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS // Med. J. Aust. 2020. Vol. 213 (2). P. 54–56. e1. https://doi.org/10.5694/mja2.50674.
Pierrakos C., Karanikolas M., Scolletta S. et al. Acute respiratory distress syndrome: pathophysiology and therapeutic options // J. Clin. Med. Res. 2012. Vol. 4 (1). P. 7–16. https://doi.org/10.4021/jocmr761w.
Торкунов П.А., Шабанов П.Д. Токсический отек легких: патогенез, моделирование, методология изучения // Обзоры по клинической фармакологии и лекарственной терапии. 2008. Т. 6. № 2. C. 3–54 [Torkunov P.A., Shabanov P.D. Toksicheskij otek legkih: patogenez, modelirovanie, metodologiya izucheniya // Obzory po klinicheskoj farmakologii i lekarstvennoj terapii. 2008. Vol. 6. N. 2. P. 3–54 (In Russ.)].
Шефтель В.О., Дышиневич Н.Е., Сова Р.В. Токсикология полимерных материалов / Киев: Здоровье, 1988. С. 77–78 [Sheftel’ V.O., Dyshinevich N.E., Sova R.V. Toksikologiya polimernyh materialov / Kiev: Zdorov’e, 1988. P. 77–78 (In Russ.)].
Matute-Bello G., Downey G., Moore B.B. et al. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals // Am. J. Respir. Cell Mol. Biol. 2011. Vol. 44 (5). P. 725–738. https://doi.org/10.1165/rcmb.2009-0210ST.
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