The effects of hypocalcemia on spatial alternans and ventricular fibrillation studied with the optical mapping technique

The heart is a wonderful but complex organ: it uses electrochemical mechanisms in order to produce mechanical energy to pump the blood throughout the body and allow the life of humans and animals. This organ can be subject to several diseases and sudden cardiac death (SCD) is the most catastrophic manifestation of these diseases, responsible for the death of a large number of people throughout the world. It is estimated that 325000 Americans annually die for SCD. SCD most commonly occurs as a result of reentrant tachyarrhythmias (ventricular tachycardia (VT) and ventricular fibrillation (VF)) and the identification of those patients at higher risk for the development of SCD has been a difficult clinical challenge. Nowadays, a particular electrocardiogram (ECG) abnormality, “T-wave alternans” (TWA), is considered a precursor of lethal cardiac arrhythmias and sudden death, a sensitive indicator of risk for SCD. TWA is defined as a beat-to-beat alternation in the shape, amplitude, or timing of the T-wave on the ECG, indicative of the underlying repolarization of cardiac cells [5]. In other words TWA is the macroscopic effect of subcellular and celluar mechanisms involving ionic kinetics and the consequent depolarization and repolarization of the myocytes. Experimental activities have shown that TWA on the ECG is a manifestation of an underlying alternation of long and short action potential durations (APDs), the so called APD-alternans, of cardiac myocytes in the myocardium. Understanding the mechanism of APDs-alternans is the first step for preventing them to occur. In order to investigate these mechanisms it’s very important to understand that the biological systems are complex systems and their macroscopic properties arise from the nonlinear interactions among the parts. The whole is greater than the sum of the parts, and it cannot be understood only by studying the single parts. In this sense the heart is a complex nonlinear system and its way of working follows nonlinear dynamics; alternans also, they are a manifestation of a phenomenon typical in nonlinear dynamical systems, called “period-dubling bifurcation”. Over the past decade, it has been demonstrated that electrical alternans in cardiac tissue is an important marker for the development of ventricular fibrillation and a significant predictor for mortality. It has been observed that acute exposure to low concentration of calcium does not decrease the magnitude of alternans and sustained ventricular Fibrillation (VF) is still easily induced under these condition. However with prolonged exposure to low concentration of calcium, alternans disappears, but VF is still inducible. This work is based on this observation and tries to make it clearer. The aim of this thesis is investigate the effect of hypocalcemia spatial alternans and VF doing experiments with canine hearts and perfusing them with a solution with physiological ionic concentration and with a solution with low calcium concentration (hypocalcemia); in order to investigate the so called memory effect, the experimental activity was modified during the way. The experiments were performed with the optical mapping technique, using voltage-sensitive dye, and a custom made Java code was used in post-processing. Finding the Nolasco and Dahlen’s criterion [8] inadequate for the prediction of alternans, and takin into account the experimental results, another criterion, which consider the memory effect, has been implemented. The implementation of this criterion could be the first step in the creation of a method, AP-based, discriminating who is at risk if developing VF. This work is divided into four chapters: the first is a brief presentation of the physiology of the heart; the second is a review of the major theories and discovers in the study of cardiac dynamics; the third chapter presents an overview on the experimental activity and the optical mapping technique; the forth chapter contains the presentation of the results and the conclusions.

A new concept for a Sport-Coupè car developed with the Industrial Design Structure method (IDeS)

The aim of this study, conducted in collaboration with Lawrence Technological University in Detroit, is to create, through the method of the Industrial Design Structure (IDeS), a new concept for a sport-coupe car, based on a restyling of a retro model (Ford Mustang 1967). To date, vintage models of cars always arouse great interest both for the history behind them and for the classic and elegant style. Designing a model of a vehicle that can combine the charm of retro style with the innovation and comfort of modern cars would allow to meet the needs and desires of a large segment of the market that today is forced to choose between past and future. Thanks to a well-conceived concept car an automaker company is able to express its future policy, to make a statement of intent as, such a prototype, ticks all the boxes, from glamour and visual wow-factor to technical intrigue and design fascination. IDeS is an approach that makes use of many engineering tools to realize a study developed on several steps that must be meticulously organized and timed. With a deep analysis of the trends dominating the automotive industry it is possible to identify a series of product requirements using quality function deployment (QFD). The considerations from this first evaluation led to the definition of the technical specifications via benchmarking (BM) and top-flop analysis (TFA). Then, the structured methodology of stylistic design engineering (SDE) is applied through six phases: (1) stylistic trends analysis; (2) sketches; (3) 2D CAD drawings; (4) 3D CAD models; (5) virtual prototyping; (6) solid stylistic model. Finally, Developing the IDeS method up to the final stages of Prototypes and Testing you get a product as close as possible to the ideal vehicle conceptualized in the initial analysis.