Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Model driven design for embedded systems

Questo lavoro di tesi si focalizza sulla modellazione di sistemi software in grado far interagire piattaforme elettroniche differenti tra loro.

Numerical and experimental investigation of structural stiffness influence on ratcheting convection cell in granular soils under cyclic loading

Lateral cyclic loaded structures in granular soils can lead to an accumulation of irreversible strains by changing their mechanical response (densification) and forming a closed convective cell in the upper layer of the bedding. In the present thesis the convective cell dimension, formation and grain migration inside this closed volume have been studied and presented in relation to structural stiffness and different loads. This relation was experimentally investigated by applying a cyclic lateral force to a scaled flexible vertical element embedded in dry granular soil. The model was monitored with a camera in order to derive the displacement field by means of the PIV technique. Modelling large soil deformation turns out to be difficult, using mesh-based methods. Consequently, a mesh-free approach (DEM) was chosen in order to investigate the granular flow with the aim of extracting interesting micromechanical information. In both the numerical and experimental analyses the effect of different loading magnitudes and different dimensions of the vertical element were considered. The main results regarded the different development, shape and dimensions of the convection cell and the surface settlements. Moreover, the Discrete Element Method has proven to give satisfactory results in the modelling of large deformation phenomena such as the ratcheting convective cell.