Computational analysis of β-adrenergic stimulation and its effects on cardiac ventricular electrophysiology

Research output: ThesisDoctoral ThesisInternal

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Abstract

Cardiovascular disorders often (~50% of the cases) manifest themselves suddenly in the form of ventricular arrhythmias leading to sudden cardiac death. The autonomic nervous system plays an important role in the induction of these arrhythmias, but the exact mechanisms contributing at the level of the individual cell remain incompletely understood. In this thesis, a systems-biology approach was used in which computer models were developed to investigate the effect of sympathetic stimulation (“stress”) on the electrophysiology of the cardiac ventricular myocyte. Using these models, the consequences of mutations in cardiac ion channels and/or pharmacological interventions were investigated and the ionic mechanisms were determined. Together with experimental research, this has provided novel insights into the cellular mechanisms contributing to “stress”-induced arrhythmias. These computational models provide a state-of-the-art framework to investigate cardiac electrophysiology and could in the future form the basis of novel approaches for personalized medicine by integrating available patient-specific information.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Maastricht University
Supervisors/Advisors
  • Crijns, Harry, Supervisor
  • Peeters, Ralf, Supervisor
  • Volders, Paul, Advisor
  • Westra, Ronald, Advisor
Award date27 Apr 2012
Place of PublicationMaastricht
Publisher
Print ISBNs9789461908742
Publication statusPublished - 1 Jan 2012

Keywords

  • arrhythmias
  • electrophysiology
  • computer models
  • systems-biology

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