Browsing by Subject "cardiac"
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Item Understand and analyzing APD alternans(2015-10) McIntyre, StephenA beat-to-beat alternation in the action potential duration (APD) of myocytes, i.e. alternans, is believed to be a direct precursor of ventricular fibrillation in the whole heart. A common approach for the prediction of alternans is to construct the restitution curve, which is the nonlinear functional relationship between the APD and the preceding diastolic interval (DI). It was proposed that alternans appears when the magnitude of the slope of the restitution curve exceeds one, known as the restitution hypothesis. In this thesis we aim at understanding the spatio-temporal formation of alternans. Our goal is threefold. First we show, in silico with periodic pacing, that APD and calcium alternans develops locally in a small region before spreading to the rest of the domain and that the slope of the restitution curve for cells in the said small region is different than the restitution curve of cells which exhibit alternans at a later time. These results are in agreement with experimental data. The restitution hypothesis was derived under the assumption of periodic stimulation, when there is a dependence of the DI on the immediate preceding APD (i.e. feedback). However, under physiological conditions, the heart rate exhibits substantial variations in time, known as heart rate variability (HRV). Our second goal is to investigate the role of HRV in the alternans formation in isolated cardiac myocytes using numerical simulations of an ionic model of the cardiac action potential. We use two different pacing protocols: a periodic pacing protocol with feedback and a protocol without feedback and show that when HRV is incorporated in the periodic pacing protocol, it facilitates alternans formation in the isolated cell. Furthermore we show that the magnitude of alternans does not change significantly. In the case of the pacing protocol without feedback, alternans formation is prevented, even in the presence of HRV. Lastly, we derive a probabilistic model that incorporates HRV in a restitution curve. We show that this model conserves probability and that it has eigenvalue \lambda=1 for all parameters and eigenvalue \lambda=-1 under certain conditions. We derive a numerical scheme that conserves probability and present numerical results using a simple restitution curve.Item Utility of Monophasic Action Potentials in the Diagnosis and Treatment of Cardiac Arrhythmias(2018-04) Schmidt, MeganThe object of this thesis was to investigate applications for monophasic action potential (MAP) recordings in the diagnosis and treatment of cardiac arrhythmias. To meet this objective, MAPs were measured in situ and in vitro, during sinus rhythm and cardiac arrhythmias. MAPs were analyzed for potential clinical applications and in novel cardiac mapping and ablation catheter concepts. MAPs are focal action potential recordings which are directly proportional to the electrical activities of cells adjacent to a contacting electrode. When sufficient force is applied between a contacting electrode and the myocardium, the cells directly beneath become mechanically depolarized; i.e. electrically inactive. As a transmembrane action potential passes through this region, a change in boundary currents between the active and inactive cells, via gap junctions, results in a waveform that is proportional to the original action potential. The Visible Heart® Apparatus provides us with the ability to study large mammalian hearts, including human, in an in vitro setting; allowing the testing of prototype catheter concepts prior to in situ or in vivo work. To validate MAPs from an in vitro working heart model a comparison study was conducted. Over the course of 2 hours in situ and 2 hours in vitro MAPs were recorded from the right atrium, left atrium, and right ventricle (endocardially and epicardially). Overall, there were no significant differences between recorded signals when compared to in situ baseline recordings. Based on these findings, systems like the Visible Heart® Apparatus can be used as a platform on which cardiac action potentials can be studied. The clinical application of MAP recordings, as they pertain to radiofrequency (RF) ablations, was also evaluated. To ensure proper lesion formation, RF ablation requires a catheter contact force (CF) of between 10-20 grams to be maintained throughout energy delivery. It was determined that MAP waveforms could only be recorded when at least 10-15 grams of CF was applied to the myocardium. In other words, the presence of MAP waveforms would indicate that sufficient CF has been applied prior to the delivery of RF energy. Additionally, MAP waveforms were found to correlate with RF lesion size. MAP amplitudes at baseline (pre-ablation) were significantly larger than amplitudes from lesions which matured to greater than 1 mm deep. MAPs were also able to distinguish between lesions between 1-2mm deep, and those deeper than 2mm. Moving forward, MAPs may be used in evaluating cardiac viability, both through recording from induced lesions, as well as in regions of scarred or ischemic myocardium.