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Full-Text Articles in Engineering
Molecular Basis Of Class Ib Drug Interactions With The Nav Channel Macromolecular Complex: A Route To Personalized Medicine For Cardiac Arrhythmia, Wandi Zhu
McKelvey School of Engineering Theses & Dissertations
The heart rhythm is precisely controlled by the electrical impulse that propagate in the cardiac tissue. In single cardiomyocytes, the electrical activity generated by action potentials (AP). Cardiac NaV channels (NaV1.5) carry a large influx of Na+ that mediates the initiation and propagation of the AP in both atria and ventricles. Disruption of NaV1.5 function by genetic variants or external factors can result in deadly arrhythmias, such as long QT syndrome and Brugada syndrome. Thus, NaV channels are import therapeutic targets. The class I antiarrhythmics are the modulators of the NaV channels. Although they have been used clinically for over …
Transcriptional Regulation Of Arrhythmia: From Mouse To Human, Yun Qiao
Transcriptional Regulation Of Arrhythmia: From Mouse To Human, Yun Qiao
McKelvey School of Engineering Theses & Dissertations
In the last two decades, our understanding of cardiac arrhythmias has been accelerated immensely by the development of genetically engineered animals. Transgenic and knockout mice have been the “gold standard” platforms for delineating disease mechanisms. Much of our understanding of the pathogenesis of atrial and ventricular arrhythmias is gained from mouse models that alter the expression of specific ion channels or other proteins. However, cardiac arrhythmias such as atrial fibrillation are heterogeneous diseases with numerous distinct conditions that could not be explained exclusively by the disruption of ionic currents. Increasing evidence suggests disruption of signaling pathways in the pathogenesis of …
Development Of High Resolution Tools For Investigating Cardiac Arrhythmia Dynamics, Christopher Reed Gloschat
Development Of High Resolution Tools For Investigating Cardiac Arrhythmia Dynamics, Christopher Reed Gloschat
McKelvey School of Engineering Theses & Dissertations
Every year 300,000 Americans die due to sudden cardiac death. There are many pathologies, acquired and genetic, that can lead to sudden cardiac death. Regardless of the underlying pathology, death is frequently the result of ventricular tachycardia and/or fibrillation (VT/VF). Despite decades of research, the mechanisms of ventricular arrhythmia initiation and maintenance are still incompletely understood.
A contributing factor to this lack of understanding is the limitations of the investigative tools used to study VT/VF. Arrhythmias are organ level phenomena that are governed by cellular interactions and as such, near cellular levels of resolution are needed to tease out their …
Calcium Cycling Disturbances And Arrhythmogenesis, Namit Gaur
Calcium Cycling Disturbances And Arrhythmogenesis, Namit Gaur
McKelvey School of Engineering Theses & Dissertations
In this work, a detailed multiscale computational model of Ca cycling and action potential in a ventricular myocyte is developed and used to study mechanisms of arrhythmias associated with mutations in the ryanodine receptor (RyR). The multiscale ventricular myocyte model reproduces experimentally observed Ca dynamics both at the local dyadic scale and at the global whole-cell scale, while also simulating the action potential (AP) shaped by membrane ionic currents. The model represents stochastic activation of L-type Ca channels (LCCs) and RyRs in the dyads and simulates random generation of Ca sparks both during excitation-contraction coupling (ECC) and during diastole. The …