Liquid respiratory desaturation. The first experience of application on large biological objects

Introduction. This article is a continuation of the publication of the experimental studies results of prevention of acute decompression sickness (aDCS) in laboratory animals by the method of liquid respiratory desaturation (LRDS). LRDS is a method of preventing decompression disorders by the excretion of metabolically indifferent gases (in particular nitrogen) from the body during spontaneous respiration with liquid or artificial liquid lung ventilation (ALLV), by dissolved gas concentration gradient "from tissues to respiratory fluid". The method allows to provide rapid desaturation of the body from metabolically indifferent gases in the process of liquid respiration before and/or during decompression, thereby creating conditions for application of ultra-fast decompression profiles without the risk of decompression disorders.

The aim of the study was to confirm the possibility of LRDS being a method of DCS prevention on large laboratory animals (minipigs).

Materials and methods. The studies were performed on Wiessenau minipigs (n=8) — male and female, aged 4–5.5 months and weighing 7.1–11.2 kg. Animals of the control (n=4) and experimental (n=4) groups were subjected by compression by keeping in an air environment under high pressure (absolute 0.5 MPa for 60 minutes) to saturate tissues with indifferent gas (nitrogen). After compression experimental group was exposed to 30-minute ALLV with a liquid (perfluorodecalin) saturated with an oxygen under normobaric conditions. Air environment pressure during procedure of artificial lung ventilation was kept at 0.5 MPa. Decompression of the control and experimental groups was carried out in non-stop manner for 80 and 40 seconds respectively. The investigation of severity of clinical manifestations of DCS (changes in hemodynamic and respiratory parameters) including ultrasonic examination of gas bubbles in the heart and large vessels of the liver and as well as survival of animals in groups and pathoanatomical changes was performed.

Results of the study. Clinical manifestations, ultrasonic scanning of the heart and venous vessels of the liver, as well as morphological examination data indicated the development of severe acute post-decompression disorders (PDD) in animals of the control group, which caused deaths in 100% of cases. Meanwhile all animals in experimental group survived and their state was stable. According to ultrasonic examination, the presence of small number of gas bubbles in the right-side heart chambers and liver's venous vessels being noted, but they disappeared after several hours. Deviations of the respiration's parameters function from background values (shortness of breath of a mixed type with the participation of auxiliary muscles, etc.) observed from the 2nd to the 4th day after ALLV, as well as compensatory reactions from the cardiovascular system (heart rate variability and instability of hemodynamic parameters) were caused by ALLV.

Conclusions. Compressed air exposure 0.5 MPa for 60 minutes followed by 80 seconds of non-stop decompression allows to provoke the severe acute PDD minipigs model, manifested by pronounced intravascular gas formation, the development of acute respiratory and cardiovascular insufficiency causing the development of adverse outcomes.

The ultrasound method of visual assessment of intravascular gas formation severity, adapted for minipigs, together with the dynamics of changes in the indicators of respiratory and cardiovascular systems makes possible to assess not only state of animal under anesthesia, but also the effectiveness of PDD prevention measures.

The usage of ALLV with PFC liquid completely saturated with 100% oxygen under normobaric conditions makes possible partial removal of indifferent gas (nitrogen) dissolved in tissues of experimental animals during exposition in a compressed air environment before decompression and thereby carry out the prevention of DCS by LRDS method. It makes possible to implement successfully ultra-fast decompression profiles, incompatible with life in the control group.

The state of animals from experimental group after LRDS is characterized by lung impairment caused by ALLV in hyperbaric conditions accompanied by temporary changes of external respiration function and compensatory reactions of cardiovascular system, observed during first 4 days.

Ethics. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. The Clinical Study Protocol was approved by local Ethics Committee of The Federal State Budgetary Scientific Institution «Izmerov Research Institute of Occupational Health».

Funding. The study was funded by The Advanced Research Foundation, Moscow, Russian Federation.

Conflict of interests. The authors declare no conflict of interests.

Received: 18.13.2024 / Accepted: 25.03.2024 / Published: 05.04.2024

1. On approval of the list of occupational diseases. https://clck.ru/39WVSt (Order of the Ministry of Health and Social Development of the Russian Federation dated 04/27/2012 No. 417N (Revision dated 04/27/2012)). Access mode: free.

2. Smolin V.V., Sokolov G.M., Pavlov B.N. Diving descents up to 60 meters and their medical support. Ed. 4th, revised and expanded. M.: Firma «Slovo»; 2013.

3. Physiology of scuba diving and emergency rescue: Textbook, ed. prof. I.A. Sapova. L.: Voen-med. akad. im. S.M. Kirova, 1986. – S. 8.

4. Kylstra J.A., Tissing M.O., Van der Maen A. Of mice as fish. Trans. Am. Soc. Artif. Intern. Organs. 1962; 8: 378–83. https://doi.org/10.1097/00002480-196204000-00077

5. Gollan F., Clark L.C. Prevention of bends by breathing an organic liquid. Trans. Assoc. Am. Physicians. 1967; 29: 102–109.

6. Lynch P.R., Wilson J.S., Shaffer T.H., Cohen N. Decompression incidence in air- and liquid-breathing hamsters. Undersea Biomed Res. 1983; 10(1): 1–10.

7. Kriss A.E. Life processes and hydrostatic pressure. M.: «Nauka»; 1973.

8. Kylstra J.A., Nantz R., Crowe J., Wagner W., Saltzman H.A. Hydraulic compression of mice to 166 atmospheres. Science. 1967; 158: 793–794.

9. Kotskij M.A., Bonitenko E.Yu., Ton’shin A.A., Rodchenkova P.V. Opportunity of liquid ventilation method implementation in advanced technologies of accidental submarine crews rescue. Med. truda i prom. ekol. 2022; 62(9): 566–578. https://doi.org/10.31089/1026-9428-2022-62-9-566-578

10. Kotskij M.A., Bonitenko E.Yu., Makarov A.F., Kanibolockij A.A., Kochoyan A.L., Litvinov N.A. About possibility of using liquid respiration to prevent the development of decompression disorders. Med. truda i prom. ekol. 2022; 62(2): 91–100. https://doi.org/10.31089/1026-9428-2022-62-2-91-100

11. Kotskij M.A., Bonitenko E.Yu., Ton’shin A.A., Rodchenkova P.V., Muravskaya M.P., Tkachuk Yu.V., Kanibolockij A.A., Kochoyan A.L. Liquid respiratory desaturation is a new method of preventing decompression sickness. Med. truda i prom. ekol. 2023; 63(1): 4–17.

12. Møllerløkken A., Blogg S.L., Doolette D.J., Nishi R.Y., Pollock N.W. Consensus guidelines for the use of ultrasound for diving research caisson. Diving Hyperb. Med. 2016; 46(1): 26–32.

13. Zverev D.P., Bychkov S.A., Myasnikov A.A., Yarkov A.M., Haustov A.B., Klenkov I.R., Fokin S.G. Possibilities of ultrasound methods in the diagnosis of decompression sickness. Morskaya meditsina. 2021; 7(4): 75–83. https://doi.org/10.22328/2413-5747-2021-7-4-75-83

14. Carpenter J.W. Carpenter S. Exotic animal formulary. Elsevier Science. 2022. ISBN: 9780323833929. ISBN-10: 0323833926.