COMPARATIVE CHARACTERISTICS OF PLACENTAL AND SPLEEN CRYOEXTRACT EFFECTS ON HEART MORPHOMETRIC PARAMETERS IN AN AUTOIMMUNE MYOCARDITIS MODEL ASSESSED BY CARDIAC ULTRASOUND
DOI:
https://doi.org/10.32689/2663-0672-2024-4-4Keywords:
autoimmune myocarditis, ultrasound examination, end-diastolic diameter, end-systolic diameter, interventricular septal thicknessAbstract
Autoimmune diseases (AIDs) affect approximately 10% of the global population. As these conditions are often systemic, heart involvement is a frequent complication. In particular, myocarditis is closely linked to complex and abnormal autoimmune mechanisms. Despite its high mortality rate and potential for severe cardiac damage, treatment for myocarditis remains limited to symptomatic management. This prompted us to explore the effectiveness of biotechnological drugs, specifically cryoextracts – noncellular products developed using low-temperature processing and designed for long-term storage. The aim of the study is to characterize cardiac structure, with a focus on left ventricular morphology as assessed by ultrasound, when using placenta cryoextract and spleen cryoextract in a model of autoimmune myocarditis (AIM). Materials and methods. The effectiveness of CEP (cryoextract of placenta) and CES (cryoextract of spleen) in AIM was studied on 35 male rats weighing 200-220 g, randomized into 5 groups. Ultrasound examination of the heart was performed using the Sonomed 500 ultrasound echotomoscope (Poli-Spectrum, Ukraine) in B-mode and M-mode with a linear probe (7.5L38, 7.5 MHz) on the 28th day of the experiment. Results and Discussion. The study found that in rats with AIH, there was a statistically significant increase (p<0.001) in the left ventricular end-systolic diameter (LVD) by 47.0%, reaching 5.5±0.17 mm, indicating pronounced cardiac dilation. The thickness of the interventricular septum in diastole (IVST) increased by 30.0% compared to intact animals (p<0.001), indicating myocardial hypertrophy due to inflammation in AIH. There was also a 12.0% decrease in the relative wall thickness of the left ventricle (p=0.04), suggesting structural changes in the myocardium. Volumetric parameters, such as the end-diastolic volume and end-systolic volume (ESV), showed a tendency to increase (p>0.05), indicating left ventricular dilation in AIH without treatment. The introduction of CEP led to a decrease in the thickness of the interventricular septum (IVS) by 18.7% compared to the control (p=0.001), which indicates its effectiveness in restoring structural changes of the heart in AIM. When using CES, a decrease in the CSO by 31.7% (p=0.016) was observed, which indicates a significant improvement in left ventricular function. Conclusions. СEP administration reduced IVST by 18.7% (p=0.001), demonstrating its effectiveness in restoring structural changes in the heart in AIH, surpassing the effect of Cordarone (IVST reduction of 9.9%, p=0.01). СES also reduced IVST by 12.1% (p=0.006), confirming its potential as an alternative drug. СEP treatment decreased ESV by 62.0% (p<0.001), highlighting its cardioprotective effect. СES reduced ESV by 31.7% (p=0.016), confirming its therapeutic effect, although less pronounced than that of СEP.
References
Gracia-Ramos A. E., Martin-Nares E., Hernández-Molina G. New Onset of Autoimmune Diseases Following COVID-19 Diagnosis. Cells. 2021. № 10 (12). Р. 3592. DOI: https://doi.org/10.3390/cells10123592
Winchester N., Calabrese C., Calabrese L. H. The Intersection of COVID-19 and Autoimmunity: What is Our Current Understanding? Pathog Immun. 2021. № 6(1). Р. 31–54. DOI: https://doi.org/10.20411/pai.v6i1.417
Gazzaruso C., Carlo Stella N., Mariani G., Nai C., Coppola A., Naldani D., Gallotti P. High Prevalence of Antinuclear Antibodies and Lupus Anticoagulant in Patients Hospitalized for SARS-CoV2 Pneumonia. Clin Rheumatol. 2020. № 39(7). Р. 2095–2097. DOI: https://doi.org/10.1007/s10067-020-05180-7
Zhou Y., Han T., Chen J., Hou C., Hua L., He S., Guo Y., Zhang S., Wang Y., Yuan J., Zhao C., Zhang J., Jia Q., Zuo X., Li J., Wang L., Cao Q., Jia E. Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID-19. Clin Transl Sci. 2020. № 13 (6). Р. 1077–1086. DOI: https://doi.org/10.1111/cts.12805
Bastard P., Rosen L. B., Zhang Q., Michailidis E., Hoffmann H. H., Zhang Y., Dorgham K., Philippot Q., et al. Autoantibodies Against Type I IFNs in Patients with Life-Threatening COVID-19. Science. 2020. № 370 (6515). Р. eabd4585. DOI: https://doi.org/10.1126/science.abd4585
Bhatraju P. K., Ghassemieh B. J., Nichols M., Kim R., Jerome K. R., Nalla A. K., Greninger A. L., Pipavath S., Wurfel M. M., Evans L., Kritek P. A., West T. E., Luks A., Gerbino A., Dale C. R., Goldman J. D., O'Mahony S., Mikacenic C. COVID-19 in Critically Ill Patients in the Seattle Region – Case Series. N Engl J Med. 2020. № 382 (21). Р. 2012–2022. DOI: https://doi.org/10.1056/NEJMoa2004500
Shi S., Qin M., Shen B., Cai Y., Liu T., Yang F., Gong W., Liu X., Liang J., Zhao Q., Huang H., Yang B., Huang C. Association of Cardiac Injury with Mortality in Hospitalized Patients with COVID-19 in Wuhan, China. JAMA Cardiol. 2020. № 5 (7). Р. 802–810. DOI: https://doi.org/10.1001/jamacardio.2020.0950
Channappanavar R., Perlman S. Pathogenic Human Coronavirus Infections: Causes and Consequences of Cytokine Storm and Immunopathology. Semin Immunopathol. 2017. № 39 (5). Р. 529–539. DOI: https://doi.org/10.1007/s00281-017-0629-x
Huang K. J., Su I. J., Theron M., Wu Y. C., Lai S. K., Liu C. C., Lei H. Y. An Interferon-Gamma-Related Cytokine Storm in SARS Patients. J Med Virol. 2005. № 75 (2). Р. 185–194. DOI: https://doi.org/10.1002/jmv.20255
Dominguez-Erquicia P., Dobarro D., Raposeiras-Roubín S., Bastos-Fernandez G., Iñiguez-Romo A. Multivessel Coronary Thrombosis in a Patient with COVID-19 Pneumonia. Eur Heart J. 2020. № 41 (22). Р. 2132. DOI: https://doi.org/10.1093/eurheartj/ehaa393
Hua A., O'Gallagher K., Sado D., Byrne J. Life-Threatening Cardiac Tamponade Complicating Myo-Pericarditis in COVID-19. Eur Heart J. 2020. № 41 (22). Р. 2130. DOI: https://doi.org/10.1093/eurheartj/ehaa253
Dabbagh M. F., Aurora L., D'Souza P., Weinmann A. J., Bhargava P., Basir M. B. Cardiac Tamponade Secondary to COVID-19. JACC Case Rep. 2020. № 2 (9). Р. 1326–1330. DOI: https://doi.org/10.1016/j.jaccas.2020.04.009
Desai S. R., Wong J., Suhitharan T., Chan Y. W., Ng S. Y. Point of Care Ultrasound: A Clinical Decision Support Tool for COVID-19. Singapore Med J. 2023. № 64 (4). Р. 226–236. DOI: https://doi.org/10.11622/smedj.2021098
Gawałko M., Balsam P., Lodziński P., Grabowski M., Krzowski B., Opolski G., Kosiuk J. Cardiac Arrhythmias in Autoimmune Diseases. Circ J. 2020. № 84 (5). Р. 685–694. DOI: https://doi.org/10.1253/circj.CJ-19-0705
Tschöpe C., Ammirati E., Bozkurt B., Caforio A. L. P., Cooper L. T., Felix S. B., Hare J. M., Heidecker B., Heymans S., Hübner N., Kelle S., Klingel K., Maatz H., Parwani A. S., Spillmann F., Starling R. C., Tsutsui H., Seferovic P., Van Linthout S. Myocarditis and Inflammatory Cardiomyopathy: Current Evidence and Future Directions. Nat Rev Cardiol. 2021. № 18 (3). Р. 169–193. DOI: https://doi.org/10.1038/s41569-020-00435-x
Liu T., Fu Y., Shi J., He S., Chen D., Li W., Chen Y., Zhang L., Lv Q., Yang Y., Jin Q., Wang J., Xie M. Noninvasive Ultrasound Stimulation to Treat Myocarditis Through Splenic Neuro-Immune Regulation. J Neuroinflammation. 2023. № 20 (1). Р. 94. DOI: https://doi.org/10.1186/s12974-023-02773-2
Chyzh M. O., Halchenko S. E., Hladkykh F. V., Byzov V. V., Rohoza L. A., Bielochkina I. V., Sleta I. V. Acellular Cryopreserved Biological Agents: Technology of Production and Composition Analysis. Monograph. Vinnytsia: Tvory; 2024. 264 p. DOI: https://doi.org/10.46879/2024.1
Hladkykh F. V. Evaluation of Tentative and Research Activity in Rats with Experimental Allergic Encephalomyelitis Against the Administration of Cell-Free Cryopreserved Biological Agents. Psychiatry, Neurology and Medical Psychology. 2024. № 11 (2(24)). Р. 124–137. DOI: https://doi.org/10.26565/2312-5675-2024-24-02
Hladkykh F. V. Characteristics of the Impact of Acellular Cryopreserved Biological Agents on Antioxidant-Prooxidant Homeostasis in Heart Tissues in a Model of Autoimmune Myocarditis. Health & Education. 2024. № 2. Р. 23–30. DOI: https://doi.org/10.32782/health-2024.2.4
Hladkykh F. V. Biochemical assessment of the inflammatory process activity under the influence of cell-free cryopreserved biological agents in a rat model of autoimmune arthritis. Modern Medicine, Pharmacy, and Psychological Health. 2024. № 1 (15). Р. 8–12. DOI: https://doi.org/10.32689/2663-0672-2024-1-1.
Hladkykh F. V., Lyadova T. I., Solovyiov S. O. Features of the Hepatocyte Cell Cycle in Experimental Autoimmune Hepatitis Under the Influence of Cryoextracts from Placenta and Spleen, as Well as the Conditioned Medium of Mesenchymal Stem Cells. Clinical and Preventive Medicine. 2024. Vol. 7. № 37. Р. 24–37. DOI: https://doi.org/10.31612/2616-4868.7.2024.03
Hladkykh F. V., Liadova T. I. Experimental Study of Nephroprotective Properties of Cryoextracts of Placenta and Spleen, as Well as Conditioned Medium of Mesenchymal Stem Cells in Autoimmune Membranous Nephropathy. Ukraine. National Health. 2024. Vol. 3. № 77. Р. 106–114. DOI: https://doi.org/10.32782/2077-6594/2024.3/17
Pavlenko H. P. Free Radical, Antioxidant, and Hemocoagulation Processes are Normal in Experimental Heart Pathology and Their Limitation by a Peptide Bioregulator. Dissertation Abstract. Kharkiv. 1993. 20 p.
Hladkykh F. V. Freund’s Adjuvant is a Classic of Vaccine Adjuvants and the Basis of Experimental Immunology. The Journal of V. N. Karazin Kharkiv National University. Series Medicine. 2024. № 32 (3(50)). Р. 414–439. DOI: https://doi.org/10.26565/2313-6693-2024-50-10
Freund J. Some Aspects of Active Immunization. Annual Review of Microbiology. 1947. № 1. Р. 291–308. DOI: https://doi.org/10.1146/annurev.mi.01.100147.001451
Fontes J. A., Barin J. G., Talor M. V., Stickel N., Schaub J., Rose N. R., Cihakova D. Complete Freund’s Adjuvant Induces Experimental Autoimmune Myocarditis by Enhancing IL-6 Production During Initiation of the Immune Response. Immunity, Inflammation and Disease. 2017. № 5 (2). Р. 163–176. DOI: https://doi.org/10.1002/iid3.155
Dzhihaliuk O. V., Stepaniuk H. I., Zaitchko N. V., Kovalenko S. I., Shabelnyk K. P. Characterization of the Effect of 4-[4-Oxo-4H-Quinazolin-3-yl] Benzoic Acid (PK-66) on the Course of Adrenaline-Induced Myocardial Dystrophy in Rats Based on Biochemical Studies. Medical and Clinical Chemistry. 2016. № 18 (4). Р. 16–22. DOI: https://doi.org/10.11603/mcch.2410-681X.2016.v0.i4.7249
Rybolovlev Yu. R., Rybolovlev R. S. Dosage of Substances for Mammals According to Biological Activity Constants. Proceedings of the Academy of Sciences of the USSR. 1979. № 247 (6). Р. 1513–1516.
Shepitko V. I. Structural and Functional Indicators of the Cryopreserved Liver and the Effect of Its Transplantation on the Morphofunctional State of a Number of Internal Organs: Dissertation. Kharkiv, 2004. 326 p. Access: https://nrat.ukrintei.ua/searchdoc/0504U000610/
Bespalova I. G. Peptide Composition and Biological Action of Extracts of Cryopreserved Pig Spleen Fragments and Piglet Skin. Dissertation. Kharkiv, 2016. 162 p. Access: https://nrat.ukrintei.ua/searchdoc/0416U004539/
Root-Bernstein R., Fairweather D. Unresolved Issues in Theories of Autoimmune Disease Using Myocarditis as a Framework. Journal of Theoretical Biology. 2015. № 375. Р. 101–123. DOI: https://doi.org/10.1016/j.jtbi.2014.11.022
Chyzh M.O., Manchenko A.O., Trofimova A.V., Belochkina I.V. Ultrasound Assessment of Heart Remodelling Affected by Therapeutic Hypothermia and MSC on Myocardial Infarction Model. Ukrainian Journal of Radiology and Oncology. 2020. № 3(28). Р. 222–240. DOI: https://doi.org/10.46879/ukroj.3.2020.222-240
Chyzh M. O., Belochkina I. V., Globa V. Yu., Sleta I. V., Mikhailova I. P., Hladkykh F. V. Ultrasound Examination of Rat Hearts After Experimental Epinephrine-Induced Damage and the Application of Heart Xenoextract. The Journal of V.N. Karazin Kharkiv National University. Series Medicine. 2024. № 32 (2(49)). Р. 185–197. DOI: https://doi.org/10.26565/2313-6693-2024-49-06
Devereux R. B., Alonso D. R., Lutas E. M., Gottlieb G. J., Campo E., Sachs I., Reichek N. Echocardiographic Assessment of Left Ventricular Hypertrophy: Comparison to Necropsy Findings. American Journal of Cardiology. 1986. № 57 (6). Р. 450–458. DOI: https://doi.org/10.1016/0002-9149(86)90771-x
Zar J. H. Biostatistical Analysis (5 ed.). Prentice-Hall, Englewood. 2014. 960 p.
