Putting Heart into Research

There is currently no ideal model of the human adult heart for use in research. This might not sound that important, but the heart is really important in drug research; many new drugs fall at the last hurdle because of negative, long-term, side effects on the heart such as longer than normal recharge between beats. This prevents the heart from working effectively and electrical disturbances like this can lead to sudden cardiac death, not an ideal outcome of a treatment.

Lack of an ideal heart model thus leads to the use of animals as they provide successful, whole-body responses. It breaks my heart when I look at my rabbit companion, Esmeralda (below), and imagine her being treated that way. While I cannot deny that animals have been invaluable in learning as much as we know today about our bodies and the medicines we take, I cannot condone it still being a scientific standard now that we understand their level of consciousness. But what can be used to replace a heart in drug research?

Currently, it is possible to isolate individual heart muscle cells (called myocytes) from the myocardium, but they lack cell to cell interaction and most of their morphology and function is lost within minutes. In other words, much like all of us last year, within the first few minutes of isolation they miss talking to each other and start to deteriorate! These cells are ineffective in any kind of research, let alone when studying the long-term effect of drugs. Instead, it is now possible to cut thin slices of the heart muscle tissue (myocardium) and keep them alive in the lab under controlled conditions. This method allows the cells to maintain native interactions. 

The heart is built of several layers of tissue: The myocardium is a thick muscular layer (dark red coloured section of bottom image) responsible for maintaining the structure of the heart and keeping it pumping.
(Sengenes and Ancel, 2017).

The slices provide a promising approach to modelling the heart, compliant with the three R’s of animal research; reduce the use of animals, replace animals and refine methods used to reduce harm (read more here). Slices can even be taken from animals sacrificed for food, meaning reduced intentional animal euthanasia for research. 

Now we just need to work on ways to improve slice longevity. Incubating the slices in appropriate medium provides hormones and growth factors aiming to enhance metabolic activity for extended periods. To confirm the slices are functioning like heart tissue should, a special camera can track the edges of the tissue in response to electrical stimulation to measure contractility. Electrically stimulating regions around the edges of the slice can also highlight the propagation of electrical activity, providing insight into conduction properties. Once we have data regarding optimum parameters of the slices, we can develop an ex vivo model (real tissue, alive outside of the body) for use in chronic drug research. 

It is imperative that we develop a successful model of the heart, not only because it will save lives of countless animals, but also to reduce the cost, improve time efficiency and enhance the development of new drugs.

Further Reading

  1. The 3 R’s: National Centre for the Replacement Refinement & Reduction of Animals in Research (2020), Available at: https://www.nc3rs.org.uk/the-3rs
  2. Living myocardial slices: a novel multicellular model for cardiac translational research: Perbellini, F. and Thum, T. (2020), European Heart Journal, 41(25), pp. 2405-2408. Available at: https://academic.oup.com/eurheartj/article/41/25/2405/5621351
  3. Biomimetic electromechanical stimulation to maintain adult myocardial slices in vitro: Watson, S., Duff, J., Bardi, I., Zabielska, M., Atanur, S., Jabbour, R., Simon, A., Tomas, A., Smolenski, R., Harding, S., Perbellini, F. and Tettacciano, C. (2019), nature communications, 10(2168). Available at: https://www.nature.com/articles/s41467-019-10175-3
  4. Comprehensive Physiology: Chapter – Role of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat?: Senegenes, C. and Ancel, P., (2017), [Internet]. New Jersey: John Wiley & Sons, Inc.; 2017. Available for download at: https://www.researchgate.net/publication/318156924_Role_of_Epicardial_Adipose_Tissue_in_Health_and_Disease_A_Matter_of_Fat )