PhD defence Melania Buonocunto

Keywords: Arrhythmias, Computational modelling, Stretch-activated ion channels, Mechano-electric feedback

"Stretching boundaries Bridging mechanical and electrical functions of the heart: a multiscale in silico characterization of the pro-arrhythmic effects of stretch-activated ion channels"

How dangerous is it when a ball or punch suddenly hits your chest? This research tries to understand what happens behind the scenes, focusing on how mechanical impacts disrupt the heart’s electrical rhythm. Through computer simulations, this thesis investigates the role of stretch-sensitive switches in the heart, called Stretch-Activated Channels (SACs), which mediates this mechano-electric blackout.

The computational method used was transversal, bridging from the single heart cell level, up to the tissue, and finally to the context of real genetic heart diseases.

The simulations showed that the timing and intensity of the impact are critical: mechanical stress applied with the wrong conditions can trigger an extra, dangerous beat or eventually lead to sudden cardiac death. Furthermore, in computer models of people with certain genetic heart conditions, SACs activation made arrhythmias much more likely. This work provides fundamental insights into how physical forces contribute to heart disease, paving the way for better understanding and potential treatments.

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