Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in
Cuiping Liang1, Qince Li1,2, Kuanquan Wang1
1School of Computer Science and Technology, Harbin Institute of Technology (HIT), Harbin, China.
Insights
This study models myocardial ischemia, injury, and infarction (MI) to understand arrhythmias. It reveals that varied conduction velocities and reduced safety factors in damaged heart tissue trigger reentrant waves, crucial for developing new arrhythmia therapies.
Area of Science:
- Cardiovascular Physiology
- Computational Biology
- Cardiac Electrophysiology
Background:
- Myocardial ischemia, injury, and infarction (MI) are stages of acute coronary syndrome (ACS).
- Reentrant arrhythmias are linked to myocardial ischemia or MI, but mechanisms in remodeled ischemic hearts remain unclear.
- Previous research often studied ischemia or MI individually.
Purpose of the Study:
- To develop biophysical single-cell and tissue models of ischemia stages (1a, 1b, MI) to mimic electrophysiological remodeling in ACS.
- To investigate mechanisms of reentrant wave initiation during ischemia progression using 2D and 3D models.
- To provide insights into arrhythmic risk and guide therapies for ischemia-related arrhythmias.
Main Methods:
- Created detailed biophysical single-cell models for ischemia 1a, 1b, and MI.
- Constructed 2D tissue models with varying distributions of ischemic and infarcted areas.
- Simulated wave propagation and analyzed vulnerable windows, conduction velocity, and safety factors.
- Developed a 3D model using patient MRI data to observe reentrant waves in a scar.
Main Results:
- Vulnerable windows in combined ischemic conditions correlated with wave dynamics in single conditions.
- Reentrant waves were induced by abrupt conduction velocity changes at the ischemia 1b/MI border.
- Decreased safety factors in MI regions, due to increased excitation thresholds, also contributed to reentrant wave initiation.
- Reentrant wave formation was successfully simulated in a 3D patient-specific scar model.
Conclusions:
- Electrophysiological remodeling across different stages of acute coronary syndrome (ACS) significantly impacts arrhythmogenesis.
- Heterogeneity in conduction velocity and reduced safety factors are key mechanisms driving reentrant arrhythmias in ischemic heart disease.
- Understanding these multi-stage pathological processes is vital for developing effective anti-arrhythmic therapies.
Abstract:
Myocardial ischemia, injury and infarction (MI) are the three stages of acute coronary syndrome (ACS). In the past two decades, a great number of studies focused on myocardial ischemia and MI individually, and showed that the occurrence of reentrant arrhythmias is often associated with myocardial ischemia or MI. However, arrhythmogenic mechanisms in the tissue with various degrees of remodeling in the ischemic heart have not been fully understood. In this study, biophysical detailed single-cell models of ischemia 1a, 1b, and MI were developed to mimic the electrophysiological remodeling at different stages of ACS. 2D tissue models with different distributions of ischemia and MI areas were constructed to investigate the mechanisms of the initiation of reentrant waves during the progression of ischemia. Simulation results in 2D tissues showed that the vulnerable windows (VWs) in simultaneous presence of multiple ischemic conditions were associated with the dynamics of wave propagation in the tissues with each single pathological condition. In the tissue with multiple pathological conditions, reentrant waves were mainly induced by two different mechanisms: one is the heterogeneity along the excitation wavefront, especially the abrupt variation in conduction velocity (CV) across the border of ischemia 1b and MI, and the other is the decreased safe factor (SF) for conduction at the edge of the tissue in MI region which is attributed to the increased excitation threshold of MI region. Finally, the reentrant wave was observed in a 3D model with a scar reconstructed from MRI images of a MI patient. These comprehensive findings provide novel insights for understanding the arrhythmic risk during the progression of myocardial ischemia and highlight the importance of the multiple pathological stages in designing medical therapies for arrhythmias in ischemia.
More Related Videos
Related Concept Videos
01:28Mechanism of Cardiac Arrhythmias
01:19Electrophysiology of Normal Cardiac Rhythm
01:25ECG Interpretation of Arrhythmias II: Atrial, Junctional and Ventricular Arrhythmias