Miquel Bosch: Effects of reactive oxygen species in the development of cardiac arrhythmias

Miquel Bosch successfully defended his Bachelor thesis in Physics Engineering in 9th July 2019

Effects of reactive oxygen species in the development of cardiac arrhythmias

Among all ions present in a cardiac cell, calcium is categorically the most important. It governs the contraction and relaxation of the heart chambers that enables pumping of blood throughout the body. Calcium mishandling is highly related to heart diseases such as arrhythmia, which is one of the major causes of death in developed countries. The conditions for which calcium mishandling appears and the exact role the ion plays in the development of arrhythmia, however, are not fully understood.

Recently, new chemical compounds have been reported to aect the aforementioned mechanisms and its relation with the appearance of pro-arrhythmic situations is yet to be studied. These compounds are reactive oxygen species (ROS), which are chemically active molecules containing oxygen. ROS are known to tune cardiac functioning under healthy conditions, but under pathophysiological conditions its effects may divert and promote the rise of arrhythmogenic behavior.

In this project, a model of the ryanodine receptor (RyR), the sarcoplasmic reticulum release channel, is proposed. Accounting for oxidation processes mediated by ROS, opening and inactivation processes mediated by calcium it is possible to explain several mishandling situations and give an explanation for them, therefore suggesting a possible treatment. More specifically, instabilities that arise in the core of the model directly translate into incorrect functioning of the cardiac cell.

The model reproduces known experimental results such as calcium waves, increase in frequency of calcium sparks and tuning of normal RyR functioning. In addition, other arrhythmogenic behaviors can be infered from the model, as it gives rise to [Ca2+] oscillations due to oxidized RyR sensitivity. For a narrow range of this magnitude these even turn chaotic, showing a very rich dynamical behaviour that is directly linked to calcium mishandling. Consequently, it is possible to conclude that when oxidized, enhanced RyR sensitivity is responsible for the appearance of arrhythmia precursors at the subcellular level.