Quantitative and qualitative analysis components the myocardium of rats in hypoxia
DOI:
https://doi.org/10.26641/1997-9665.2023.4.14-21Keywords:
tissue hypoxia, cardiomyocyte, contractile apparatus, ultrastructure, myofibrils.Abstract
Background. Various types of hypoxia occur during fetal development and early neonatal phases, influenced by factors that complicate pregnancy. Given the frequency of cardiovascular issues, understanding the impact of antenatal hypoxia on newborn hearts and exploring corrective measures is crucial in medical research and practice. Objective. The study focuses on analyzing the quantitative and qualitative composition of contractile cardiomyocytes as the primary cell population in elements of the myocardial contractile apparatus. It involves examining the proliferative variability of components of the myocardial contractile apparatus under conditions of modeled hypoxia of varying types. Additionally, it includes a quantitative and qualitative analysis of the cellular composition of myocardial elements in adult rats and their offspring subjected to various types of hypoxia during prenatal development. Methods. The study was conducted on sexually mature female Wistar rats (4-5.5 months) and their offspring – newborn rats (14, 16, 20 Prenatal and 1 day Postnatal). The Results. Under the influence of chronic hypoxia on the 14th day of prenatal development, different areas of the atrial myocardium demonstrated significantly different thickness values. The values of this indicator in the second experimental group did not significantly differ from the control group values at this term. The effect on the 16th day of prenatal development affected the proliferative activity. Following exposure to chronic hypoxia, this measure in newborn rats significantly increased in RV, and in the LV compared to the previous term. On the 16th day of prenatal development, the thickness values of the atrial and auricular myocardium in animals from the first experimental group did not significantly differ from the values of the previous term and the control group. The myocardial thickness on the 20th day after the influence did not significantly differ compared to the 16th day of prenatal development and compared to the norm. The proliferative activity of atrial cardiomyocytes in animals from the first experimental group gradually decreased until the first day of postnatal development, which was reflected in the reduction in the number of Ki-67 positive cells compared to the 16th day. Conclusion. Under conditions of hypoxia and in normal conditions from the 14th day of prenatal development to the 1st day of postnatal development, the myocardial thickness demonstrates an inverse correlation with the proliferation index of atrial cardiomyocytes; under normal conditions. Hypoxia does not significantly affect the processes of proliferation of atrial cardiomyocytes.
References
- Johnson J, Mohsin S, Houser SR. Cardio-myocyte Proliferation as a Source of New Myocyte Development in the Adult Heart. Int J Mol Sci. 2021;22(15):7764. doi:10.3390/ijms22157764. PMID: 34360531; PMCID: PMC8345975.
- Sutovska H, Babarikova K, Zeman M, Molcan L. Prenatal Hypoxia Affects Foetal Cardio-vascular Regulatory Mechanisms in a Sex- and Cir-cadian-Dependent Manner: A Review. Int J Mol Sci. 2022;23(5):2885. doi:10.3390/ijms23052885. PMID: 35270026; PMCID: PMC8910900.
- Smith KLM, Swiderska A, Lock MC, Gra-ham L, Iswari W, Choudhary T, Thomas D, Kowash HM, Desforges M, Cottrell EC, Trafford AW, Giussani DA, Galli GLJ. Chronic developmental hy-poxia alters mitochondrial oxidative capacity and reactive oxygen species production in the fetal rat heart in a sex-dependent manner. J Pineal Res. 2022;73(3):12821. doi:10.1111/jpi.12821. Epub 2022 Aug 17. PMID: 35941749; PMCID: PMC9540814.
- Makkos A, Szántai Á, Pálóczi J, Pipis J, Kiss B, Poggi P, Ferdinandy P, Chatgilialoglu A, Görbe A. A Comorbidity Model of Myocardial Ische-mia/Reperfusion Injury and Hypercholesterolemia in Rat Cardiac Myocyte Cultures. Front Physiol. 2020;10:1564. doi:10.3389/fphys.2019.01564. PMID: 31992989; PMCID: PMC6962358.
- Sun Y, Jiang C, Hong H, Liu J, Qiu L, Huang Y, Ye L. Effects of hypoxia on cardiomyo-cyte proliferation and association with stage of de-velopment. Biomed Pharmacother. 2019;118:109391. doi:10.1016/j.biopha.2019.109391. Epub 2019 Aug 28. PMID: 31545287.
- Cutie S, Huang GN. Vertebrate cardiac re-generation: evolutionary and developmental per-spectives. Cell Regen. 2021;10(1):6. doi:10.1186/s13619-020-00068-y. PMID: 33644818; PMCID: PMC7917145.
- Sakaguchi A, Kimura W. Metabolic regula-tion of cardiac regeneration: roles of hypoxia, ener-gy homeostasis, and mitochondrial dynamics. Curr Opin Genet Dev. 2021;70:54-60. doi:10.1016/j.gde.2021.05.009. Epub 2021 Jun 12. PMID: 34130066.
- Ye L, Qiu L, Feng B, Jiang C, Huang Y, Zhang H, Zhang H, Hong H, Liu J. Role of Blood Oxygen Saturation During Post-Natal Human Car-diomyocyte Cell Cycle Activities. JACC Basic Transl Sci. 2020;5(5):447-460. doi:10.1016/j.jacbts.2020.02.008. PMID: 32478207; PMCID: PMC7251192.
- Castillo-Casas JM, Caño-Carrillo S, Sánchez-Fernández C, Franco D, Lozano-Velasco E. Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart-Part II: Molecular Mechanisms of Cardiac Regeneration. J Cardiovasc Dev Dis. 2023;10(9):357. doi:10.3390/jcdd10090357. PMID: 37754786; PMCID: PMC10531542.
- Fantini E, Demaison L, Sentex E, Grynberg A, Athias P. Some biochemical aspects of the pro-tective effect of trimetazidine on rat cardiomyo-cytes during hypoxia and reoxygenation. J Mol Cell Cardiol. 1994;26(8):949-58. doi:10.1006/jmcc.1994.1116. PMID: 7799450.
- Gettayacamin M, Retnam L. AAALAC In-ternational Standards and Accreditation Process. Toxicol Res. 2017;33(3):183-189. doi:10.5487/TR.2017.33.3.183. Epub 2017 Jul 15. PMID: 28744349; PMCID: PMC5523556.
- Louhimies S. Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes. Altern Lab Anim. 2002;30(2):217-219. doi:10.1177/026119290203002S36. PMID: 12513679.
- National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th edition. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54050/ doi:10.17226/12910
- Ducsay CA, Goyal R, Pearce WJ, Wilson S, Hu XQ, Zhang L. Gestational Hypoxia and Devel-opmental Plasticity. Physiol Rev. 2018;98(3):1241-1334. doi:10.1152/physrev.00043.2017. PMID: 29717932; PMCID: PMC6088145.
- Litviňuková M, Talavera-López C, Maatz H, Reichart D, Worth CL, Lindberg EL, Kanda M, Polanski K, Heinig M, Lee M, Nadelmann ER, Rob-erts K, Tuck L, Fasouli ES, DeLaughter DM, McDonough B, Wakimoto H, Gorham JM, Samari S, Mahbubani KT, Saeb-Parsy K, Patone G, Boyle JJ, Zhang H, Zhang H, Viveiros A, Oudit GY, Bay-raktar OA, Seidman JG, Seidman CE, Noseda M, Hubner N, Teichmann SA. Cells of the adult human heart. Nature. 2020;588(7838):466-472. doi:10.1038/s41586-020-2797-4. Epub 2020 Sep 24. PMID: 32971526; PMCID: PMC7681775.
- Lozano-Velasco E, Garcia-Padilla C, Del Mar Muñoz-Gallardo M, Martinez-Amaro FJ, Caño-Carrillo S, Castillo-Casas JM, Sanchez-Fernandez C, Aranega AE, Franco D. Post-Transcriptional Regula-tion of Molecular Determinants during Cardiogene-sis. Int J Mol Sci. 2022;23(5):2839. doi:10.3390/ijms23052839. PMID: 35269981; PMCID: PMC8911333.
- Romanowicz J, Guerrelli D, Dhari Z, Mul-vany C, Reilly M, Swift L, Vasandani N, Ramadan M, Leatherbury L, Ishibashi N, Posnack NG. Chron-ic perinatal hypoxia delays cardiac maturation in a mouse model for cyanotic congenital heart disease. Am J Physiol Heart Circ Physiol. 2021;320(5):1873-1886. doi:10.1152/ajpheart.00870.2020. Epub 2021 Mar 19. PMID: 33739154; PMCID: PMC8163656.
- Cohen ED, Yee M, Porter GA Jr, Ritzer E, McDavid AN, Brookes PS, Pryhuber GS, O'Reilly MA. Neonatal hyperoxia inhibits proliferation and survival of atrial cardiomyocytes by suppressing fatty acid synthesis. JCI Insight. 2021;6(5):140785. doi:10.1172/jci.insight.140785. PMID: 33507880; PMCID: PMC8021108.
- Tong W, Xue Q, Li Y, Zhang L. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats. American Journal of Physiology-Heart and Circulatory Physiology. 2011;301(5):2113-2121.
- Wang H, Paulsen MJ, Hironaka CE, Shin HS, Farry JM, Thakore AD, Jung J, Lucian HJ, Eskandari A, Anilkumar S, Wu MA, Cabatu MC, Steele AN, Stapleton LM, Zhu Y, Woo YJ. Natural Heart Regeneration in a Neonatal Rat Myocardial Infarction Model. Cells. 2020;9(1):229. doi:10.3390/cells9010229. PMID: 31963369; PMCID: PMC7017245.
- Wang H, Wisneski A, Imbrie-Moore AM, Paulsen MJ, Wang Z, Xuan Y, Lopez Hernandez H, Hironaka CE, Lucian HJ, Shin HS, Anilkumar S, Thakore AD, Farry JM, Eskandari A, Williams KM, Grady F, Wu MA, Jung J, Stapleton LM, Steele AN, Zhu Y, Woo YJ. Natural cardiac regeneration con-serves native biaxial left ventricular biomechanics after myocardial infarction in neonatal rats. J Mech Behav Biomed Mater. 2022;126:105074. doi:10.1016/j.jmbbm.2022.105074. Epub 2022 Jan 4. PMID: 35030471; PMCID: PMC8899021.
- Guo QY, Yang JQ, Feng XX, Zhou YJ. Re-generation of the heart: from molecular mecha-nisms to clinical therapeutics. Mil Med Res. 2023;10(1):18. doi:10.1186/s40779-023-00452-0. PMID: 37098604; PMCID: PMC10131330.
- Leite MR, Cestari IA, Cestari IN. Computa-tional tool for morphological analysis of cultured neonatal rat cardiomyocytes. Annu Int Conf IEEE Eng Med Biol Soc. 2015;2:3517-3520. doi:10.1109/EMBC.2015.7319151. PMID: 26737051.
- Teng Q, He X, Luo D, Wang Z, Zhou B, Yuan Z, Tao D. [Image processing applying in anal-ysis of motion features of cultured cardiac myocyte in rat]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2007;24(1):5-8. Chinese. PMID: 17333881.
- Jiang XY, Zhang L, Yu C, Jiang H, Li J. [Research for a better method of neonatal rat cardi-ac myocytes, primary culture and purification]. Si-chuan Da Xue Xue Bao Yi Xue Ban. 2015;46(2):301-304. Chinese. PMID: 25924451.
- Wang YZ, Luo JD. [Reactive oxygen spe-cies mediate cultured neonatal rat cardiac myocyte hypertrophy induced by endothelin-1]. Sheng Li Xue Bao. 2004;56(3):403-406. Chinese. PMID: 15224158.
- Chen CL, Shen T, Zheng M, Guo YH, Zhu XJ, Chen GH. [Inhibition of cardiac hypertrophy by mitofusin 2 in neonatal rat cardiomyocytes]. Beijing Da Xue Xue Bao Yi Xue Ban. 2008;40(5):528-532. Chinese. PMID: 18931719.
- Shevchenko KM. Morphological features of atrial myocardium embryonic development and its changes caused by hypoxia effect. Regul Mech Biosyst. 2019;10(1):129-35.
- Bourdier G, Détrait M, Bouyon S, Lemarié E, Brasseur S, Doutreleau S, Pépin JL, Godin-Ribuot D, Belaidi E, Arnaud C. Intermittent Hypoxia Trig- gers Early Cardiac Remodeling and Contractile Dys- function in the Time-Course of Ischemic Cardiomy- opathy in Rats. J Am Heart Assoc. 2020;9(16):16369.
- Tverdokhlib IV, Marchenko DG. [Ultra-structural changes of the rat contractile myocardial apparatus during prenatal ontogenesis in norm and after alcohol influence]. World of Medicine and Biology. 2019;15(69):225-230. Ukrainian.
- Marchenko DG, Tverdokhlib IV. [Ontoge-netic mechanisms of contractive apparatus devel-opment in cardiomyocytes]. Morphologia. 2012;6(4):5-11. Ukrainian.
- Ivanchenko MV, Tverdokhlib IV. [For-mation of mitochondrial apparatus of contractile cardiomyocytes during normal and hypoxic injury of cardiogenesis]. Morphologia. 2013;7(1):5-20. Ukrainian.
- Lew RA, Baertschi AJ. Mechanisms of hy-poxia-induced atrial natriuretic factor release from rat hearts. Am J Physiol. 1989;257(1(2)):147-156. doi:10.1152/ajpheart.1989.257.1.H147. PMID: 2526588.
- Baertschi AJ, Hausmaninger C, Walsh RS, Mentzer RM Jr, Wyatt DA, Pence RA. Hypoxia-induced release of atrial natriuretic factor (ANF) from the isolated rat and rabbit heart. Biochem Bi-ophys Res Commun. 1986;140(1):427-33. doi:10.1016/0006-291x(86)91108-3. PMID: 2946294.
Downloads
Published
How to Cite
Issue
Section
License

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world.
The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.
