Evaluating the dynamics of cardiovascular and respiratory system parameters and histological changes in the lungs after baclofen administration and its combination with ethanol
- Authors: Romanova O.L.1,2, Blagonravov M.L.1, Torshin V.I.1, Dzhuvalyakov P.G.1,2, Barinov E.K.1,3, Ershov A.V.4,5
-
Affiliations:
- Peoples' Friendship University of Russia
- Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution "Petrovsky National Research Centre of Surgery"
- Russian University of Medicine
- The First Sechenov Moscow State Medical University
- V.A. Negovsky Research Institute of General Reanimatology of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
- Issue: Vol 10, No 4 (2024)
- Pages: 474-485
- Section: Original study articles
- URL: https://journal-vniispk.ru/2411-8729/article/view/288317
- DOI: https://doi.org/10.17816/fm16139
- ID: 288317
Cite item
Full Text
Abstract
Background: Baclofen is a selective agonist of γ-aminobutyric acid B receptors. The drug exhibits pronounced psychotropic effects and frequently causes dependence. However, its impact on the cardiovascular and respiratory systems remains underexplored.
Aim: To evaluate the dynamics of specific functional parameters of the cardiovascular and respiratory systems, as well as histological changes in the lungs, in cases of baclofen poisoning and its combination with ethanol.
Materials and methods: Baclofen and its combination with ethanol were administered to rats under general anesthesia (chloral hydrate 300 mg/kg, intramuscularly). Animals in the control group (n=5) Submitted no baclofen or ethanol. Animals in Groups 1, 3, and 5 were administered baclofen at a dose of 85 mg/kg, with physiological parameters recorded at 3, 4.5, and 24 hours. Animals in Groups 2, 4, and 6 were administered baclofen at the same dose combined with 40% ethanol (7 ml/kg). Physiological parameters (oxygenation level, red blood cell count per liter of blood, and hemoglobin concentration in g/L) were recorded at the same time points. The animals were then euthanized by cervical dislocation under general anesthesia (chloral hydrate), and biological material was collected for subsequent studies. Morphometric analysis was performed using G.G. Avtandilov’s grid.
Results: Baclofen and its combination with ethanol led to a statistically significant decrease in oxygenation levels. Red blood cell count and hemoglobin concentration (g/L) remained unchanged. A dynamic complex of pathological changes developed in the lungs of experimental animals, including microcirculation disturbances, thickening of interalveolar septa due to edema, and leukocyte infiltration. Three hours after combined administration of baclofen and ethanol, a statistically significant increase in vessel area was observed. At 4.5 hours, the areas occupied by leukocytes, the ratio of leukocyte area to interalveolar septa area, and the area affected by edema increased significantly. After 24 hours, the leukocyte area, the ratio of leukocyte area to interalveolar septa area, and the edema area further increased.
Conclusion: Combined with chemical-toxicological findings, the data obtained from this study allow for the identification of baclofen poisoning, estimation of the time elapsed since poisoning, and assessment of exposure conditions. Understanding the processes occurring in the lungs following baclofen and ethanol administration may enhance the effectiveness of medical assistance for affected individuals.
Full Text
##article.viewOnOriginalSite##About the authors
Olga L. Romanova
Peoples' Friendship University of Russia; Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution "Petrovsky National Research Centre of Surgery"
Author for correspondence.
Email: olgpharm@yandex.ru
ORCID iD: 0000-0001-6356-9251
SPIN-code: 6727-9170
Cand. Sci. (Вiology)
Russian Federation, Moscow; MoscowMikhail L. Blagonravov
Peoples' Friendship University of Russia
Email: blagonravov_ml@pfur.ru
ORCID iD: 0000-0001-7838-0486
SPIN-code: 1050-0527
MD, Dr. Sci. (Medicine), Professor
Russian Federation, MoscowVladimir I. Torshin
Peoples' Friendship University of Russia
Email: vtorshin@mail.ru
ORCID iD: 0000-0002-3950-8296
SPIN-code: 8602-3159
MD, Dr. Sci. (Medicine), Professor
Russian Federation, MoscowPavel G. Dzhuvalyakov
Peoples' Friendship University of Russia; Avtsyn Research Institute of Human Morphology of Federal state budgetary scientific institution "Petrovsky National Research Centre of Surgery"
Email: fred197490@gmail.com
ORCID iD: 0000-0003-1709-2418
SPIN-code: 5925-7780
MD, Dr. Sci. (Medicine), Professor
Russian Federation, Moscow; MoscowEvgeniy Kh. Barinov
Peoples' Friendship University of Russia; Russian University of Medicine
Email: ev.barinov@mail.ru
ORCID iD: 0000-0003-4236-4219
SPIN-code: 2112-4568
MD, Dr. Sci. (Medicine), Professor
Russian Federation, Moscow; MoscowAnton V. Ershov
The First Sechenov Moscow State Medical University; V.A. Negovsky Research Institute of General Reanimatology of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology
Email: salavatprof@mail.ru
ORCID iD: 0000-0001-5758-8552
SPIN-code: 2059-3248
MD, Dr. Sci. (Medicine), Professor
Russian Federation, Moscow; MoscowReferences
- Simonova AY, Ilyashenko KK, Klychnikova EV, et al. Parameters of the blood oxidant/antioxidant system in elderly patients with acute poisoning. Obshchaya reanimatologiya = General Reanimatol. 2022;18(3):38–44. EDN: RIJJYL doi: 10.15360/1813-9779-2022-3-38-44
- Sinenchenko AG, Batotsyrenov CB, Lodyagin AN, et al. Delirium in acute poisoning with 1,4-butanediol and its correction. Obshchaya reanimatologiya = General Reanimatol. 2021;17(6):42–48. EDN: JFZCOS doi: 10.15360/1813-9779-2021-6-42-48
- Świątek G, Tkaczyk R, Radoniewicz-Tchórz A, et al. Baclofen: A great chance or danger ― discussion of poisoning based on research. J Education Health Sport. 2023;45:86–106. doi: 10.12775/JEHS.2023.45.01.006
- Drugs.com [Internet]. Baclofen (Monograph) [Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP]. Available from: https://www.drugs.com/monograph/baclofen.html. Accessed: 08.02.2024.
- Product Information Clofen. TGA eBusiness Services [2017 June 7]. Millers Point, Australia:Alphapharm Pty Limited; 2017. [https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-CMI-04976-3] Accessed: 08.02.2024.
- TGA eBusiness Services. Australian Product Information Bacthecal. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2015-PI-02261-1. Accessed: 08.02.2024.
- Chapman RW, Hey JA, Rizzo CA, Bolser DC. GABAB receptors in the lung. Trends Pharmacological Sci. 1993;14(1):26–29. doi: 10.1016/0165-6147(93)90110-6
- FDA Full Prescribing Information [Internet]. Gablofen (Baclofen). US Food and Drug Administration, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022462s013lbl.pdf. Accessed: 08.02.2024.
- McLaughlin MJ, He Y, Brunstrom-Hernandez J, et al. Response in children with cerebral palsy. PMR. 2018;10(3):235–243. doi: 10.1016/j.pmrj.2017.08.441
- Navarrete-Opazo A, Gonzalez W, Nahuelhual P. Effectiveness of oral baclofen for spasticity in children with cerebral palsy. Arch Physical Med Rehab. 2016;97(4):604–618. doi: 10.1016/j.apmr.2015.08.417
- Lake W, Shah H. Intrathecal baclofen infusion for the treatment of movement disorders. Neurosurg Clin N Am. 2019;30(2): 203–209. doi: 10.1016/j.nec.2018.12.002
- Liu J, Wang LN. Baclofen for alcohol withdrawal. Cochrane Database Systematic Rev. 2017;2017(8):CD008502. EDN: YJFAOP doi: 10.1002/14651858.CD008502.pub6
- Pierce M, Sutterland A, Beraha EM, et al. Efficacy, tolerability, and safety of low-dose and high-dose baclofen in the treatment of alcohol dependence: A systematic review and meta-analysis. Eur Neuropsychopharmacol. 2018;28(7):795–806. EDN: YJOWLB doi: 10.1016/j.euroneuro.2018.03.017
- Agabio R, Sinclair JM, Addolorato G, et al. Baclofen for the treatment of alcohol use disorder: The cagliari statement. Lancet Psychiatry. 2018;5(12):957–960. doi: 10.1016/S2215-0366(18)30303-1
- Bareli T, Ahdoot HL, Ben Moshe H, et al. Novel opipramol-baclofen combination alleviates depression and craving and facilitates recovery from substance use disorder: An animal model and a human study. Front Behav Neurosci. 2021;(15):788708. doi: 10.3389/fnbeh.2021.788708
- Balerio GN, Rubio MC. Baclofen analgesia: Involvement of the GABAergic system. Pharmacol Res. 2002;46(3):281–286. EDN: BCWRFH doi: 10.1016/s1043-6618(02)00147-0
- Moffat AC, Osselton MD, Widdop B. Clarke’s analysis of drugs and poisons. London: Pharmac Press edited; 2020.
- Leung NY, Whyte IM, Isbister GK. Baclofen overdose: Defining the spectrum of toxicity. Emerg Med Australas. 2006;18(1):77–82. doi: 10.1111/j.1742-6723.2006.00805.x
- Beraha E, Bodewits P, van den Brink W, Wiers R. Speaking fluently with baclofen. BMJ Case Reports. 2017;2017:bcr2016218714. doi: 10.1136/bcr-2016-218714
- Katyal R, Samkutty D, Muzammil SM, Saucedo S. Baclofen toxicity presenting as myoclonic status epilepticus. Neurol Clin Pract. 2019;9(6):516–518. doi: 10.1212/CPJ.0000000000000686
- Wolf ME, Mosnaim AD. Baclofen-induced manic symptoms: Case report and systematic review. Psychosomatics. 2017;58(1):94. doi: 10.1016/j.psym.2016.08.004
- Ryu HU, Kim JH, Shin BS, Kang HG. Serial electroencephalography changes in low-dose baclofen intoxication. QUIMS. 2023;13(10):7404–7409. doi: 10.21037/qims-23-630
- Mikhaylov AY, Berezina IY, Potskhveriya MM, Sumsky LI. Electroencephalography showing dying brain in a patient with acute baclofen poisoning. Zhurnal im. N.V. Sklifosovskogo "Neotlozhnaya meditsinskaya pomoshch" = Sklifosovsky J Emergency Med Care. 2017;6(4):371–375. EDN: YLJKIK doi: 10.23934/2223-9022-2017-6-4-371-375
- Charifou Y, Martinet O, Jabot J, et al. Baclofen intoxication cases in an intensive care unit. Anaesth Crit Care Pain Med. 2016;35(2):169–170. doi: 10.1016/j.accpm.2015.10.003
- De Marcellus C, le Bot S, Decleves X, et al. Report of severe accidental baclofen intoxication in a healthy 4-year-old boy and review of the literature. Arch Pediatr. 2019;26(8): 475–478. doi: 10.1016/j.arcped.2019.10.003
- Drevin G, Briet M, Ghamrawi S, et al. Baclofen overdose following recreational use in adolescents and young adults: A case report and review of the literature. Forensic Sci Int. 2020;316:110541. doi: 10.1016/j.forsciint.2020.110541
- Pelerin JM, Fristot L, Gibaja V, et al. Non-medical use of baclofen: A case series and review of the literature. Therapies. 2023:78(6):615–637. EDN: QFSPYU doi: 10.1016/j.therap.2023.02.007
- Directive 2010/63/EU of the European Parliament and the Councilof the European Union on the Protection of Animals used for scientific purposes. Saint Petersburg: Rus-LASA NP Association of Specialists Working with Laboratory Animals; 2012. 48 р. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32010L0063. Accessed: 08.02.2024.
- Bavrina AP. Modern rules for the use of descriptive statistics methods in biomedical research. Med Almanac. 2020;(2):95–104. EDN: UCVXIX
- Mizuta K, Xu D, Pan Y, et al. GABAA receptors are expressed and facilitate relaxation in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2008;294(6):1206–1216. doi: 10.1152/ajplung.00287.2007
Supplementary files
