3 years ago

Mechanisms linking T-wave alternans to spontaneous initiation of ventricular arrhythmias in rabbit models of long QT syndrome.

Zhilin Qu, Michael B Liu, Bum-Rak Choi, Gideon Koren, Tae Yun Kim, Weiqing Liu, Xiaodong Huang
T-wave alternans (TWA) and irregular beat-to-beat T-wave variability or T-wave lability (TWL), the ECG manifestations of action potential duration (APD) alternans and variability, are precursors of ventricular arrhythmias in long QT syndromes. TWA and TWL in patients tend to occur at normal heart rates and are usually potentiated by bradycardia. Whether or how TWA and TWL at normal or slow heart rates are causally linked to arrhythmogenesis remains unknown. In this study, we used computer simulations and experiments of a transgenic rabbit model of long QT syndrome to investigate the underlying mechanisms. Computer simulations showed that APD prolongation and slowed heart rates caused early afterdepolarizations mediated APD alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD alternans and chaos exacerbated pre-existing APD dispersion, and APD chaos could also induce APD dispersion de novo via chaos desynchronization. Increased APD dispersion, combined with substantially enhanced ICa,L , resulted in a tissue-scale dynamical instability to cause spontaneous occurrence of unidirectionally propagating premature ventricular complexes (PVCs) originating from the APD gradient region. These PVCs could directly degenerate into reentrant arrhythmias without the need for an additional tissue substrate or could block the following sinus beat to result in a longer RR interval which further exacerbated the APD dispersion to cause spontaneous occurrence of ventricular arrhythmias. Slow heart rate induced PVC alternans was observed in experiments of transgenic LQT2 rabbits under isoproterenol, associated with increased APD dispersion and spontaneous occurrence of ventricular arrhythmias, agreeing with the theoretical predictions. This article is protected by copyright. All rights reserved.

Publisher URL: http://doi.org/10.1113/JP275492

DOI: 10.1113/JP275492

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.