The effectiveness of hypercapnic-hypoxic training to increase resistance to acute hypoxia in rats with LPS-induced endotoxemia

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Severe sepsis (endotoxicosis), similar to cytokine storm, is aggravated by acute respiratory failure, hypotension, hypoxemia and hypercapnia, which is the main cause of high mortality. The aim of the work is to study the effectiveness of hypercapnic-hypoxic training for the relief of cardiorespiratory disorders and increased tolerance to acute hypoxia in rats with LPS-induced endotoxicosis. The experiments were conducted on anesthetized male Wistar rats. Endotoxicosis was simulated by administration of LPS (Escherchia coli) 7 mg/kg. The assessment of resistance to hypoxia was carried out by the rebreathing method (RM) with a gradual decrease in oxygen in the rebreather from 21% to the onset of apnea. 3 groups of animals were studied: I – control – NaCl, II – LPS, III – LPS+HHT. The following parameters were recorded: external respiration, mean blood pressure (APm.), saturation (SpO2), fraction of inhaled O2 (FiO2) and CO2 (FiCO2), time of onset of apnea, the amount of spontaneous respiratory recovery (autoresuscitation) in the posthypoxic period. The LPS+HHT group was previously subjected to hypercapnic-hypoxic training. For this purpose, the rebreather was filled with room air, the volume of which was selected in such a way that during the breathing of the animal into / out of the rebreather, FiO2 decreased to 11 ± 0.5% for 3 minutes, and FiCO2 increased to 5.0 ± 0.5%, after which the rat was switched to breathing air. The training regime consisted of 3 cycles: 3 min – HHT, 5 min – normoxia. It was found that the maximum decrease in resistance to acute hypoxia was observed in rats with LPS, respiratory recovery after apnea was carried out in 10%, HHT prevented a fatal decrease in SpO2 and APm, autoresuscitation occurred in 100% of cases. Based on the data obtained, it can be concluded that the combined effects of hypercapnia and hypoxia effectively contribute to increased tolerance to acute hypoxia in rats with LPS-induced endotoxemia.

Sobre autores

Zh. Donina

Pavlov Institute of Physiology the Russian Academy of Sciences

Autor responsável pela correspondência
Email: zdonina@mail.ru
Rússia, St. Petersburg

Bibliografia

  1. Симбирцев АС, Тотолян АА (2015) Цитокины в лабораторной диагностике. Инфекц болезни: новости, мнение, обучение 2: 82–98. [Simbirtsev AS, Totolyan AA (2015) Cytokines in laboratory diagnostics. Infect diseases: news, opinion, education 2: 82–98. (In Russ)].
  2. Jacono FJ, Mayer CA, Hsieh Y-H, Wilson G, Dick T (2011) Lung and brainstem cytokine levels are associated with breathing pattern changes in a rodent model of acute lung injury. Respirat Physiol Neurobiol 178(3): 429–438. https://doi.org/10.1016/j.resp.2011.04.022
  3. Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D (2020) Respiratory drive in the acute respiratory distress syndrome: Pathophysiology, monitoring, and therapeutic interventions. Intensiv Care Med 46 (4): 606–618. https://doi:org/10.1007/s00134-020-05942-6
  4. Saas P, Fan G-C (2023) Editorial: Hypoxia and inflammation: A two-way street. Front Immunol 14: 1171116. https://doi:org/10.3389/fimmu.2023.1171116
  5. Angus DC, van der Poll T (2013) Severe sepsis and septic chock. New Engl J Med 69: 840–851. https://doi:org/10.1056/NEJMra1208623
  6. Cecconi M, Evans L, Levy M, Rhodes A (2018) Sepsis and septic shock. Lancet 392(10141): 75–87. https://doi:org/10.1016/S0140-6736(18)30696-2
  7. Yıldırım F, Karaman İ, Kaya A (2021) Current situation in ARDS in the light of recent studies: Classification, epidemiology and pharmacotherapeutics. Tuberk Toraks 69(4): 535–546. 10.5578/tt.20219611' target='_blank'>https://doi: 10.5578/tt.20219611
  8. Ярошецкий АИ, Грицан АИ, Авдеев СН, Власенко АВ, Еременко АА, Заболотских ИБ, Зильбер АП, Киров МЮ, Лебединский КМ, Лейдерман ИН, Мазурок ВА, Николаенко ЭМ, Проценко ДН, Солодов АА (2020) Диагностика и интенсивная терапия острого респираторного дистресс-синдрома (Клинические рекомендации Общероссийской общественной организации “Федерация анестезиологов и реаниматологов”). Анестезиол и реаниматол (2): 5–39. [Yaroshetsky AI, Gritsan AI, Avdeev SN, Vlasenko AV, Eremenko AA, Zabolotskikh IB, Zilber AP, Kirov MYu, Lebedinskii KM, Leyderman IN, Mazurok VA, Nikolaenko EM, Protsenko DN, Solodov AA (2020) Diagnostics and intensive therapy of Acute Respiratory Distress Syndrome (Clinical guidelines of the Federation of Anesthesiologists and Reanimatologists of Russia). Russ J Anaesthesiol Reanimatol (2): 5–39. (In Russ)]. https://doi:org/10.17116/anaesthesiology20200215
  9. Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. New England J Med 342: 1301–1308. https://doi:org/10.1056/NEJM200005043421801
  10. Morales-Quinteros L, Camprubi-Rimblas M, Bringue J, Bos LD, Schultz MJ, Artigas A (2019) The role of hypercapnia in acute respiratory failure. Intensive Care Med Exp 7: 39–50. https://doi:org/10.1186/s40635-019-0239-0
  11. Quinteros LM, Roque JB, Kaufman D, Raventos AA (2019) Importance of carbon dioxide in the critical patient: Implications at the cellular and clinical levels. Med Intensive 43: 234–242. https://doi:org/10.1016/j.medin.2018.01.005
  12. Агаджанян НА, Елфимов АИ (1986) Функции организма в условиях гипоксии-гиперкапнии. М. Медицина. [Aghajanyan NA, Elfimov AI (1986). Body functions in conditions of hypoxia-hypercapnia. Medicina. M. (In Russ)].
  13. Chonghaile MN, Higgins BD, Costello J, Laffey JG (2008) Hypercapnic acidosis attenuates lung injury induced by established bacterial pneumonia. Anesthesiology 109: 837–848. https://doi:org/10.1097/ALN.0b013e3181895fb7
  14. Wu SY, Wu CP, Kang BH, Li MH, Chu SJ, Huang KL (2012) Hypercapnic acidosis attenuates reperfusion injury in isolated and perfused rat lungs. Crit Care Med 40: 553–559. https://doi:org/10.1097/CCM.0b013e318232d776
  15. Гридин ЛА (2016) Современные представления о физиологических и лечебно-профилактических эффектах действия гипоксии и гиперкапнии. Медицина 4(3): 45–68. [Gridin LA (2016) Modern ideas about the physiological and therapeutic-preventive effects of hypoxia and hypercapnia. Medicina 4(3): 45–68. (In Russ)].
  16. Rivers RJ, Meininger CJ (2023) The Tissue Response to Hypoxia: How therapeutic carbon dioxide moves the response toward homeostasis and away from instability. Int J Mol Sci 24(6): 5181–5199. https://doi:org/10.3390/ijms24065181
  17. Abolhassani M, Guais AP, Sasco AJ, Schwartz L (2009) Carbon dioxide inhalation causes pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 296(4): 657–665. https://doi:org/10.1152/ajplung.90460.2008
  18. Колчинская АЗ, Цыганова ТН, Остапенко ЛА (2003) Нормобарическая интервальная гипоксическая тренировка в медицине и спорте: Руководство для врачей. Медицина. М. [Kolchinskaya AZ, Cyganova TN, Ostapenko LA (2003) Normobaric interval hypoxic training in medicine and sports: A guide for doctors. Medicina. M. (In Russ)].
  19. Rybnikova EA, Nalivaeva NN, Zenko MY, Baranova KA (2022) Intermittent hypoxic training as an effective tool for increasing the adaptive potential, endurance and working capacity of the brain. Front Neurosci: 941740. https://doi:org/10.3389/fnins.2022.941740
  20. Supriya R, Singh K, Gao Y, Tao D, Cheour S, Dutheil F, Baker J (2023) Mimicking gene–environment interaction of higher altitude dwellers by intermittent hypoxia training: COVID-19 Preventive strategies. Biology (Basel) 12(1): 6–21. https://doi:org/10.3390/biology12010006
  21. Li G, Guan Y, Gu Y, Guo M, Ma W, Shao Q, Liu L, Ji X (2023) Intermittent hypoxic conditioning restores neurological dysfunction of mice induced by long-term hypoxia. CNS Neurosci Therap 29: 202–217. https://doi:org/10.1111/cns.13996
  22. Donina ZhA (2024) Preconditioning with moderate hypoxia increases tolerance to subsequent severe hypoxia in rats with LPS-induced endotoxemia. J Evol Biochem Physiol 60(3): 1213.
  23. Алексеева ТМ, Ковзелев ПД, Топузова МП, Сергеева ТВ, Трегуб ПП (2019) Гиперкапнически-гипоксические дыхательные тренировки как потенциальный способ реабилитационного лечения пациентов, перенесших инсульт. Артер гипертен 25(2): 134–142. [Alekseeva TM, Kovzelev PD, Topuzova MP, Sergeeva TV, Tregub PP (2019) Hypercapnic-hypoxic breathing exercises as a potential method of rehabilitation treatment of stroke patients. Arterial Hyperten 25(2): 134–142. (In Russ)]. https://doi.org/10.18705/1607-419X-2019-25-2-134-142
  24. Трегуб ПП, Малиновская НА, Куликов ВП, Кузовков ДА (2021) Гиперкапния и ее сочетание с гипоксией снижают проницаемость гематоэнцефалического барьера у крыс. Патол физиол экспер терапия 65(2): 30–36 [Tregub PP, Malinovskaya NA, Kulikov VP, Kuzovkov DA (2021) Hypercapnia and its combination with hypoxia reduce the permeability of the blood-brain barrier in rats. Pathol Physiol Exper Therapy 65(2): 30–36. (In Russ)].
  25. Трегуб ПП (2022) Влияние гиперкапнии и гипоксии на физиологию и метаболизм церебрального эндотелия в условиях ишемии. Рос физиол журн им ИМ Сеченова 108(5): 579–593. [Tregub PP (2022) The effect of hypercapnia and hypoxia on the physiology and metabolism of the cerebral endothelium under conditions of ischemia. Russ J Physiol 108(5): 579–593. (In Russ)]. https://doi.org/10.31857/S0869813922050120
  26. Wang Z, Su F, Bruhn A, Yang X, Vincent JL (2008) Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock. Am J Respirat Crit Care Med 177(2): 178–183. https://doi.org/10.1164/rccm.200706-906OC
  27. Higgins BD, Costello J, Contreras M, Hassett P, O’Tull D, Laffey JG (2009) Differential effects of buffered hypercapnia versus hypercapnic acidosis on shock and lung injury induced by systemic sepsis. Anesthesiology 111(6): 1317–1326. https://doi.org/10.1097/ALN.0b013e3181ba3c11
  28. Hanly EJ, Fuentes JM, Aurora AR, Bachman SL, De Maio A, Marohn MR, Talamini MA (2006) Carbon dioxide pneumoperitoneum prevents mortality from sepsis. Surg Endoscopy and Other Intervent Techn 20: 1482–1487. https://doi.org/10.1007/s00464-005-0246-y
  29. Galganska H, Jarmuszkiewicz W, Galganski L (2021) Carbon dioxide inhibits COVID-19-type proinflammatory responses through extracellular signal-regulated kinases 1 and 2, novel carbon dioxide sensors. Cell Mol Life Sci 78: 8229–8242. https://doi.org/10.1007/s00018-021-04005-3
  30. Laffey JG, Honan D, Hopkins N, Hyvelin JM, Boylan JF, McLoughlin P (2004) Hypercapnic acidosis attenuates endotoxin-induced acute lung injury. Am J Respirat Crit Care Med169: 46–56. https://doi.org/10.1164/rccm.200205-394OC
  31. O’Croinin DF, Nichol AD, Hopkins N, Boylan J, O’Brien S, O’Connor C, Laffey JG, McLoughlin P (2008) Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury. Crit Care Med 36: 2128–2135. https://doi.org/10.1097/CCM.0b013e31817d1b59
  32. Takeshita K, Suzuki Y, Nishio K, Takeuchi O, Toda K, Kudo H, Miyao N, Ishii M, Sato N, Naoki K, Aoki T, Suzuki K, Hiraoka R, Yamaguchi K (2003) Hypercapnic acidosis attenuates endotoxin-induced nuclear factor-[kappa] B activation. Am J Respirat Cell Mol Biol 29(1): 124–132. https://doi.org/10.1165/rcmb.2002-0126OC
  33. Contreras M, Ansari B, Curley G, Higgins BD, Hassett P, O'Toole D, Laffey JG (2012) Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-kappaB-dependent mechanism. Crit Care Med 40(9): 2622–2630. https://doi.org/10.1097/CCM.0b013e318258f8b4
  34. Tang S-E, Wu S-Y, S Chu S-J, Tzeng Y-S, Peng C-K, Lan C-C, Wann-Cherng Perng W-C, Huang K-L (2019) Pre-treatment with ten-minute carbon dioxide inhalation prevents lipopolysaccharide-induced lung injury in mice via down-regulation of Toll-Like Receptor 4 expression. Int J Mol Sci 20(24): 6293. https://doi.org/10.3390/ijms20246293
  35. Tregub PP, Kulikov VP, Ibrahimli I, Tregub OF, Volodkin AV, Ignatyuk MA, Kostin AA, Atiakshin DA (2024) Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia. Int J Mol Sci 25(7): 3665. https://doi.org/10.3390/ijms25073665
  36. Tregub P, Malinovskaya N, Hilazheva E, Morgun A, Kulikov V (2023) Permissive hypercapnia and hypercapnic hypoxia inhibit signaling pathways of neuronal apoptosis in ischemic/hypoxic rats. Mol Biol Rep 50(3): 2317–2333. https://doi.org/10.1007/s11033-022-08212-4
  37. O'Croinin BR, Young DA, Maier LE, van Diepen S, Day TA, Steinback CD (2024) Influence of hypercapnia and hypercapnic hypoxia on the heart rate response to apnea. Physiol Rep 12(11): e16054. https://doi.org/10.14814/phy2.16054

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