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The human heart, with its rhythmic beat and incredible resilience, is a marvel of biological engineering. To better understand its complexities, researchers have turned to innovative techniques, one of which is the use of living myocardial slices. These thin sections of heart tissue offer a unique glimpse into the workings of the heart and have become invaluable tools in cardiac research. In this blog article, we will dive into the world of living myocardial slices, exploring what they are, how they are prepared, and their significant contributions to our understanding of cardiac physiology and pathologies.
Living myocardial slices, often referred to simply as cardiac slices, are thin sections of heart tissue that are kept alive and functional for experimental studies. They are typically cut from the hearts of animals or, in some cases, from human donors. These slices retain the structural and functional characteristics of the heart, allowing researchers to investigate various aspects of cardiac physiology and pathophysiology.
The preparation of living myocardial slices is a delicate process that involves several key steps:
Tissue Harvesting: The first step is the careful removal of the heart from the donor organism, usually a laboratory animal, and it must be done quickly to preserve tissue viability. In the case of human myocardial slices, donors may be individuals who have donated their hearts for research purposes.
Slicing: Once the heart is harvested, it is sliced into thin sections, typically around 200 to 400 micrometers in thickness. This requires precision equipment like a vibratome or a microtome to ensure consistent and uniform slices. Z-axis deflection correction is absolutely essential, a feature the 7000smz-2 and 5100mz-Plus offer. Typical slicing parameters are:
Maintenance: Maintaining the slices in a healthy state is crucial. This involves placing them in a culture medium that provides essential nutrients and oxygen while maintaining the appropriate temperature and pH.
Experimental Studies: Once the slices are ready, researchers can conduct a wide range of experiments, including electrophysiological studies, pharmacological assessments, and the exploration of cardiac contractility, to name a few.
Living myocardial slices have made significant contributions to the field of cardiac research in several ways:
Drug Testing and Development: They are valuable tools for evaluating the effects of pharmaceuticals on the heart, which is critical for drug development and safety testing.
Electrophysiological Studies: Myocardial slices are used to study the electrical properties of the heart, helping researchers understand arrhythmias and other electrical disorders.
Disease Modeling: Researchers use cardiac slices to model and study various heart diseases, such as heart failure, ischemia, and cardiomyopathies, enabling a better understanding of disease mechanisms and potential treatments.
Functional Assessment: These slices allow scientists to assess the contractile function of heart tissue, providing insights into muscle function and response to different conditions.
Model 7000smz-2
Our top of the range high precision, vibrating microtome, this is the finest tissue slicer in the world for preparations for visual patch clamping. Shown with optional Slice incubation chamber and temperature controller.
Model 5100mz-Plus
The 5100-Plus is perfect for those who need to keep slices viable for longer e.g. for electrophysiological field recordings. The user can calibrate the Z-axis deflection of the blade to 2 µm with the adjustable blade holder and "Opti-cal" Calibration device.
Model 5100mz
The 5100mz is a very competitively priced, high precision, vibrating microtome (vibrotome for short) which shares many features with the top of the range 7000smz series, such as the vibrating mechanism, the inner and outer tissue baths and the easy to use control system.
Living myocardial slices have emerged as an indispensable tool in the realm of cardiac research. They offer a window into the intricate workings of the heart and have played a crucial role in advancing our understanding of cardiac physiology and pathologies. As technology and research methodologies continue to evolve, we can expect living myocardial slices to remain at the forefront of ground-breaking discoveries in the field of cardiology, ultimately leading to improved treatments and a deeper appreciation of the heart's complexity.
2024
Abbas, N., Bentele, M., Waleczek, F. J., Fuchs, M., Just, A., Pfanne, A., ... & Thum, T. (2024). Ex vivo modelling of cardiac injury identifies ferroptosis-related pathways as a potential therapeutic avenue for translational medicine. Journal of molecular and cellular cardiology, 196, 125-140. https://doi.org/10.1016/j.yjmcc.2024.09.012
Hancock, E. N., Palmer, B. M., & Caporizzo, M. A. (2024). Microtubule destabilization with colchicine increases the work output of myocardial slices. Journal of molecular and cellular cardiology plus, 7, 100066. https://doi.org/10.1016/j.jmccpl.2024.100066
Jordan, M., Schmieder, F., Waleczek, F. J., Polk, C., Stucki-Koch, A., Philipp, J., ... & Fiedler, J. (2024). De novo establishment of an ex vivo culture for living myocardial slices applying a microphysiological system–MPSlms. Current Directions in Biomedical Engineering (Vol. 10, No. 4, pp. 347-350). https://doi.org/10.1515/cdbme-2024-2085
Miller, J. M., Meki, M. M., El-Baz, A. S., Giridharan, G. A., & Mohamed, T. M. (2024). Culturing Cardiac Tissue Slices Under Continuous Physiological Mechanical Stretches. In Experimental Models of Cardiovascular Diseases: Methods and Protocols (pp. 61-74). New York, NY: Springer US. https://doi.org/10.1007/978-1-0716-3846-0_5
Pitoulis, F. G., Smith, J. J., Pamias‐Lopez, B., de Tombe, P. P., Hayman, D., & Terracciano, C. M. (2024). MyoLoop: Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies. Experimental Physiology, 109(3), 405-415. https://doi.org/10.1113/EP091247
Reilly-O’Donnell, B., Ferraro, E., Tikhomirov, R., Nunez-Toldra, R., Shchendrygina, A., Patel, L., ... & Gorelik, J. (2024). Protective effect of UDCA against IL-11-induced cardiac fibrosis is mediated by TGR5 signalling. Frontiers in Cardiovascular Medicine, 11, 1430772. https://doi.org/10.3389/fcvm.2024.1430772
Zabielska-Kaczorowska, M. A., Stawarska, K., Kawecka, A., Urbanowicz, K., Smolenski, R. T., & Kutryb-Zajac, B. (2024). Nucleotide depletion in hypoxia experimental models of mouse myocardial slices. Meeting Report in Nucleosides, Nucleotides & Nucleic Acids. (Vol 43, Issue 8). https://doi.org/10.1080/15257770.2024.2381791
2023
Boukhalfa, A., Robinson, S. R., Meola, D. M., Robinson, N. A., Ling, L. A., LaMastro, J. N., ... & Yang, V. K. (2023). Using cultured canine cardiac slices to model the autophagic flux with doxorubicin. Plos one, 18(3), e0282859. https://doi.org/10.1371/journal.pone.0282859
Kok, C. Y., Tsurusaki, S., Cabanes-Creus, M., Igoor, S., Rao, R., Skelton, R., ... & Kizana, E. (2023). Development of new adeno-associated virus capsid variants for targeted gene delivery to human cardiomyocytes. Molecular Therapy-Methods & Clinical Development, 30, 459-473. https://doi.org/10.1016/j.omtm.2023.08.010
Nunez-Toldra, R., Del Canizo, A., Secco, I., Nicastro, L., Giacca, M., & Terracciano, C. M. (2023). Living myocardial slices for the study of nucleic acid-based therapies. Frontiers in Bioengineering and Biotechnology, 11, 1275945. https://doi.org/10.3389/fbioe.2023.1275945
Ross, A. J., Krumova, I., Tunc, B., Wu, Q., Wu, C., & Camelliti, P. (2023). A novel method to extend viability and functionality of living heart slices. Frontiers in Cardiovascular Medicine, 10, 1244630. https://doi.org/10.3389/fcvm.2023.1244630
Wells, S. P., Raaijmakers, A. J., Curl, C. L., O’Shea, C., Hayes, S., Mellor, K. M., ... & Bell, J. R. (2023). Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats. Journal of General Physiology, 155(11), e202213296. https://doi.org/10.1085/jgp.202213296
2022
Greiner, J., Schiatti, T., Kaltenbacher, W., Dente, M., Semenjakin, A., Kok, T., ... & Rog-Zielinska, E. A. (2022). Consecutive-Day Ventricular and Atrial Cardiomyocyte Isolations from the Same Heart: Shifting the Cost–Benefit Balance of Cardiac Primary Cell Research. Cells, 11(2), 233. https://doi.org/10.3390/cells11020233
Koncz, I., Verkerk, A. O., Nicastro, M., Wilders, R., Árpádffy-Lovas, T., Magyar, T., ... & Efimov, I. R. (2022). Acetylcholine reduces IKr and prolongs action potentials in human ventricular cardiomyocytes. Biomedicines, 10(2), 244. https://doi.org/10.3390/biomedicines10020244
Kreutzer, F. P., Meinecke, A., Mitzka, S., Hunkler, H. J., Hobuß, L., Abbas, N., ... & Thum, T. (2022). Development and characterization of anti-fibrotic natural compound similars with improved effectivity. Basic Research in Cardiology, 117(1), 9. https://doi.org/10.1007/s00395-022-00919-6
Li, G., Brumback, B. D., Huang, L., Zhang, D. M., Yin, T., Lipovsky, C. E., ... & Rentschler, S. L. (2022). Acute glycogen synthase kinase-3 inhibition modulates human cardiac conduction. Basic to Translational Science, 7(10), 1001-1017. https://doi.org/10.1016/j.jacbts.2022.04.007
Ntagiantas, K., Panagopoulos, D., Poon, W. M., Kumar, J. L. M., Agha-Jaffar, D., Peters, N. S., ... & Chowdhury, R. A. (2022). Electrogram-based Estimation of Myocardial Conduction Using Deep Neural Networks. Computing in Cardiology (CinC) (Vol. 498, pp. 1-4). IEEE. https://doi.org/10.22489/CinC.2022.227
Nunez‐Toldra, R., Kirwin, T., Ferraro, E., Pitoulis, F. G., Nicastro, L., Bardi, I., ... & Terracciano, C. M. (2022). Mechanosensitive molecular mechanisms of myocardial fibrosis in living myocardial slices. ESC Heart Failure, 9(2), 1400-1412. https://doi.org/10.1002/ehf2.13832
Waleczek, F. J. G., Sansonetti, M., Xiao, K., Jung, M., Mitzka, S., Dendorfer, A., ... & Thum, T. (2022). Chemical and mechanical activation of resident cardiac macrophages in the living myocardial slice ex vivo model. Basic Research in Cardiology, 117(1), 63. https://doi.org/10.1007/s00395-022-00971-2
2021
Dries, E., Bardi, I., Nunez-Toldra, R., Meijlink, B., & Terracciano, C. M. (2021). CaMKII inhibition reduces arrhythmogenic Ca2+ events in subendocardial cryoinjured rat living myocardial slices. Journal of General Physiology, 153(6). https://doi.org/10.1085/jgp.202012737
Wülfers, E. M., Greiner, J., Giese, M., Madl, J., Kroll, J., Stiller, B., ... & Fürniss, H. E. (2021). Quantitative collagen assessment in right ventricular myectomies from patients with tetralogy of Fallot. EP Europace, 23(Supplement_1), i38-i47.https://doi.org/10.1093/europace/euaa389