Closed-loop investigation of the dynamical properties of cardiomyocyte electrophysiology by means of Dynamic clamp and Mathematical modelling

The research field of my PhD concerns mathematical modeling and numerical simulation, applied to the cardiac electrophysiology analysis at a single cell level. This is possible thanks to the development of mathematical descriptions of single cellular components, ionic channels, pumps, exchangers and subcellular compartments. Due to the difficulties of vivo experiments on human cells, most of the measurements are acquired in vitro using animal models (e.g. guinea pig, dog, rabbit). Moreover, to study the cardiac action potential and all its features, it is necessary to acquire more specific knowledge about single ionic currents that contribute to the cardiac activity. Electrophysiological models of the heart have become very accurate in recent years giving rise to extremely complicated systems of differential equations. Although describing the behavior of cardiac cells quite well, the models are computationally demanding for numerical simulations and are very difficult to analyze from a mathematical (dynamical-systems) viewpoint. Simplified mathematical models that capture the underlying dynamics to a certain extent are therefore frequently used. The results presented in this thesis have confirmed that a close integration of computational modeling and experimental recordings in real myocytes, as performed by dynamic clamp, is a useful tool in enhancing our understanding of various components of normal cardiac electrophysiology, but also arrhythmogenic mechanisms in a pathological condition, especially when fully integrated with experimental data.

Computational Modelling of Cardiac Electrophysiology: from Cell to Bedside

Heart diseases are the leading cause of death worldwide, both for men and women. However, the ionic mechanisms underlying many cardiac arrhythmias and genetic disorders are not completely understood, thus leading to a limited efficacy of the current available therapies and leaving many open questions for cardiac electrophysiologists. On the other hand, experimental data availability is still a great issue in this field: most of the experiments are performed in vitro and/or using animal models (e.g. rabbit, dog and mouse), even when the final aim is to better understand the electrical behaviour of in vivo human heart either in physiological or pathological conditions. Computational modelling constitutes a primary tool in cardiac electrophysiology: in silico simulations, based on the available experimental data, may help to understand the electrical properties of the heart and the ionic mechanisms underlying a specific phenomenon. Once validated, mathematical models can be used for making predictions and testing hypotheses, thus suggesting potential therapeutic targets. This PhD thesis aims to apply computational cardiac modelling of human single cell action potential (AP) to three clinical scenarios, in order to gain new insights into the ionic mechanisms involved in the electrophysiological changes observed in vitro and/or in vivo. The first context is blood electrolyte variations, which may occur in patients due to different pathologies and/or therapies. In particular, we focused on extracellular Ca2+ and its effect on the AP duration (APD). The second context is haemodialysis (HD) therapy: in addition to blood electrolyte variations, patients undergo a lot of other different changes during HD, e.g. heart rate, cell volume, pH, and sympatho-vagal balance. The third context is human hypertrophic cardiomyopathy (HCM), a genetic disorder characterised by an increased arrhythmic risk, and still lacking a specific pharmacological treatment.

Hybrid ground-aerial mesh networks for IoT monitoring applications: network design and software platform development

The Internet of Things (IoT) has grown rapidly in recent years, leading to an increased need for efficient and secure communication between connected devices. Wireless Sensor Networks (WSNs) are composed of small, low-power devices that are capable of sensing and exchanging data, and are often used in IoT applications. In addition, Mesh WSNs involve intermediate nodes forwarding data to ensure more robust communication. The integration of Unmanned Aerial Vehicles (UAVs) in Mesh WSNs has emerged as a promising solution for increasing the effectiveness of data collection, as UAVs can act as mobile relays, providing extended communication range and reducing energy consumption. However, the integration of UAVs and Mesh WSNs still poses new challenges, such as the design of efficient control and communication strategies. This thesis explores the networking capabilities of WSNs and investigates how the integration of UAVs can enhance their performance. The research focuses on three main objectives: (1) Ground Wireless Mesh Sensor Networks, (2) Aerial Wireless Mesh Sensor Networks, and (3) Ground/Aerial WMSN integration. For the first objective, we investigate the use of the Bluetooth Mesh standard for IoT monitoring in different environments. The second objective focuses on deploying aerial nodes to maximize data collection effectiveness and QoS of UAV-to-UAV links while maintaining the aerial mesh connectivity. The third objective investigates hybrid WMSN scenarios with air-to-ground communication links. One of the main contribution of the thesis consists in the design and implementation of a software framework called "Uhura", which enables the creation of Hybrid Wireless Mesh Sensor Networks and abstracts and handles multiple M2M communication stacks on both ground and aerial links. The operations of Uhura have been validated through simulations and small-scale testbeds involving ground and aerial devices.