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Purkinje Topology

Abstract

Defibrillation of the heart by timely application of an electric shock is now recognized as the only effective means to prevent sudden cardiac death. Despite the critical role that defibrillation therapy plays in saving human life, the understanding of the mechanisms by which electric shocks halt life-threatening arrhythmias remains incomplete.

A major factor in the formation and maintenance of cardiac arrhythmias is the specialized conduction system of the ventricles, referred to as the Purkinje system (PS). The PS is known to be potentially pro-arrhythmic under various conditions including shock-induced arrhythmogenesis, failure of defibrillation shocks or arrhythmias induced by focal activation. Surprisingly, in most studies, both experimental as well as computational, PS effects are quite often neglected. While recent advances in experimental methodology have provided new characterizations of tissue responses to externally applied electric fields, mechanistic inquiry into the biophysics of arrhythmogenesis or defibrillation is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles or in the PS. Computer models quite naturally suggest themselves as a surrogate technique to bridge the gap between experimental observations, typically recorded at the epicardial surface
of the heart, and electrical events occurring within the PS, at the ventricular epicardium or within the depth of ventricular walls. Despite major recent advancements in modeling technology, integrating topologically realistic models of the PS with anatomically and functionally realistic models of the ventricles remains to be challenging.

The overall objective of this research is, by employing realistic 3D simulations of ventricular
activation sequences, to bring a new level of understanding of the topological organization of the
PS in the rabbit ventricles and of naturally occurring inter-subject variability in topology on the
ventricular activation sequence under physiological and pathological conditions. Moreover, the
computer model will be used to study inducibility and to characterize under which conditions the
PS is pro-arrhythmic or anti-arrhythmic. Eventually, understanding the implications of the PS in the formation and maintenance of arrhythmias may pave the way to novel therapeutical approaches that make use of PS properties, to prevent the formation of arrhythmias or to facilitate a termination of arrhythmias with low-voltage defibrillation or pacing strategies.

The goal of this application is to develop new modeling tools that will enable the applicant to explore questions that remained currently unexplored. Specifically, this project proposes to examine, in anatomically and functionally detailed bidomain models of the rabbit ventricles, the role of PS topology on cardiac activation sequences under physiological and pathophysiological conditions and their impact on inducibility under various induction protocols such as shock-induced arrhythmogenesis as well as triggered activity.

Schlagworte

Elektro- und biomedizinische Technik

Medizinische Physik

Computersimulation

Defibrillation

kardiale Aktivierungssequenzen

spezielles Reizleitungssystem

Projektleitung:

Prassl Anton

Laufzeit:

01.01.2010-31.12.2011

Art der Forschung

Grundlagenforschung

Mitarbeiter*innen

Prassl A., Projektleiter*in

Beteiligte MUG-Organisationseinheiten

Lehrstuhl für Medizinische Physik und Biophysik

Lehrstuhl für Physiologie und Pathophysiologie

Projektpartner

Universidad de Extremadura, Spanien
Kontaktperson: Dr. Damián Sánchez-Quintana;

University of Calgary, Department of Electrical and Computer Engineering, Kanada
Kontaktperson: Dr. Edward J Vigmond;

Gefördert durch

Medizinische Universität Graz, Stiftingtalstraße 6, 8010 Graz, Österreich

Publizierte Projektergebnisse

> Elastic Registration of Edges using Diffuse Surfac... In: González Hidalgo, M; Mir Torres, A; Varona Gómez, J; editors(s). Tracking, Animation and Applications, Series: Lecture Notes in Computational Vision and Biomechanics. 7: Heidelberg, Deutschland: Springer-Verlag GmbH; p. 261-282. 2013(ISBN: 978-94-007-5445-4)

> Developing Microstructurally Realistic Computer Mo... EMMCOMP - 2011; DEC 9-10, 2011; Juiz de Fora, MG, BRAZIL. 2011.