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Vulnerable windows define susceptibility to alternans and spatial discordance
Seth Weinberg1, Neha Malhotra, Leslie Tung
1Department of Biomedical Engineering, The Johns Hopkins Univ. 720 Rutland Ave., Baltimore, MD 21205, USA.
Summary
Electrophysiological alternans, a precursor to arrhythmias, is influenced by temperature and pacing. Defining vulnerable windows, like the alternans vulnerable window (AVW), helps predict alternans incidence and spiral wave formation.
Area of Science:
- Cardiovascular Electrophysiology
- Computational Biology
- Arrhythmia Mechanisms
Background:
- Electrophysiological alternans, characterized by beat-to-beat variations in action potential duration and Ca(2+) transient amplitude, is implicated in ventricular arrhythmias.
- Understanding the factors influencing alternans incidence and spiral wave formation is crucial for developing antiarrhythmic strategies.
Purpose of the Study:
- To investigate the impact of pacing rate and temperature on electrophysiological alternans and spiral wave formation.
- To define and validate novel metrics, the alternans vulnerable window (AVW) and discordant alternans vulnerable window (AVW(D)), for predicting arrhythmogenesis.
Main Methods:
- Optical mapping of voltage and Ca(2+) in neonatal rat ventricular myocyte monolayers.
- Experimental manipulations including temperature changes and pharmacological interventions (pinacidil).
- Computational simulations and mathematical analysis to model alternans dynamics and validate experimental findings.
Main Results:
- Alternans incidence significantly increased at lower temperatures.
- Key pacing parameters (PCL(C), PCL(D), MCL) and vulnerable windows (AVW, AVW(D)) were temperature-dependent.
- Interventions widening AVW promoted alternans, confirmed by pinacidil experiments.
- AVW(D) size correlated with spatially discordant alternans and spiral wave formation.
Conclusions:
- Vulnerable windows, specifically AVW and AVW(D), can be quantitatively defined.
- These vulnerable windows are strongly correlated with alternans incidence, spatial discordance, and the propensity for spiral wave formation.
- The findings provide a mechanistic link between electrophysiological instability and arrhythmogenesis.
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