M.Sc. Moritz Linder

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Motivation
Patients undergoing haemodialysis (HD) have a markedly increased risk of Sudden Cardiac Death (SCD), with an incidence around 14 times higher than in the general population. The underlying mechanism often differs from that observed in patients with normal kidney function. While SCD in the general population is typically caused by fast ventricular tachyarrhythmias, events in HD patients are frequently preceded by progressive slowing of the beating rate (bradycardia), which may ultimately lead to asystole.
One possible explanation is that impaired kidney function can disrupt electrolyte balance, particularly K+ and Ca2+ levels, which are essential for normal pacemaker activity. This has also been associated with a reduced ability of the heart to increase its rate in response to sympathetic stimulation. Consistent with this mechanism, a recent case report described severe sinus node dysfunction caused by profound iatrogenic hypocalcaemia. Motivated by these observations, we investigated the mechanisms of hypocalcaemia-induced bradycardia using computational models of sinoatrial node cells. In particular, we studied how increased sympathetic stimulation may compensate for reduced beating rate and explored differences in pacemaker function between mammalian species at the single-cell level.

Student Project
To analyse how cellular variability affects pacemaker behaviour in tissue, we extended these simulations to the tissue level. For this purpose, we implemented a discrete intercellular coupling framework in openCARP based on a simplified Kirchhoff network model. A calibrated population of sinoatrial node cell models derived from the extended Severi model was embedded in a two-dimensional tissue patch, allowing us to investigate the effects of extracellular Ca2+ concentration, autonomic modulation, and intercellular coupling strength.
However, when cellular models and fibroblasts were distributed randomly across the tissue, sinoatrial node pacemaking remained surprisingly robust even under severe hypocalcaemic conditions. As a result, the simulations were not able to reproduce the hypocalcaemia-induced asystole observed clinically, suggesting that the current representation of tissue heterogeneity may be overly simplistic. The goal of this thesis project is therefore to introduce more physiologically realistic spatial heterogeneity into the tissue simulations. In particular, you will investigate spatially structured parameter variability within sinoatrial node cells and spatially structured fibroblast distributions, and analyse how these factors influence pacemaker stability under hypocalcaemic conditions.

Notes
The scope can be tailored to a bachelor’s or a master’s thesis.

Research Area
Computational Cardiac Modeling, Electrophysiology, Sinus Node

Course of Studies
Computer Science, Computational Engineering, BME, ETIT, ...

Starting Date
As soon as possible