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High-Resolution Endocardial and Epicardial Optical Mapping in a Sheep Model of Stretch-Induced Atrial Fibrillation
Published on: July 29, 2011
Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria
Barbara C Niort1,2, Alice Recalde1,2, Caroline Cros1,2
1Centre de Recherche Cardio-Thoracique de Bordeaux (CRCTB), Inserm U1045, Univeristé de Bordeaux, F-33000 Bordeaux, France.
Insights
Calcium signaling varies across the healthy left atrium, contributing to atrial fibrillation initiation. These regional differences in calcium cycling are key to understanding arrhythmia development.
Area of Science:
- Cardiovascular Physiology
- Cardiac Electrophysiology
- Arrhythmia Mechanisms
Background:
- Atrial fibrillation (AF) involves significant cardiac remodeling.
- Calcium plays a crucial role in cardiac cellular electrophysiology.
- Left atrial calcium signaling in AF remains unmapped.
Purpose of the Study:
- To investigate regional homogeneity of calcium signaling in the left atrium.
- To test if distinct left atrial regions exhibit unique calcium cycling.
- To determine the role of regional differences in pro-arrhythmic activity during AF.
Main Methods:
- Utilized a sheep model for cardiac function studies.
- Examined three left atrium regions: appendage, free wall, and pulmonary veins.
- Employed dual calcium-voltage optical mapping under control and acetylcholine-induced AF conditions.
Main Results:
- Action potential duration was uniform across regions.
- Calcium transient decay time varied significantly by region.
- AF was induced in appendage and pulmonary vein regions, but not the free wall, upon pacing.
- Dantrolene did not affect AF susceptibility.
Conclusions:
- Demonstrated heterogeneous calcium signaling across the healthy left atrium.
- Regional differences in calcium signaling may worsen during AF progression.
- These differences are crucial for focal arrhythmia initiation, independent of ryanodine receptor gating.
Background:
Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet to date, there is no information that maps calcium signaling across the left atrium.
Objective:
The aim of this study is to determine whether calcium signaling is homogenous throughout the different regions of the left atrium. This work tests the hypothesis that differences across the healthy left atrium contribute to a unique, region-dependent calcium cycling and participates in the pro-arrhythmic activity during atrial fibrillation.
Methods:
An animal model relevant to human cardiac function (the sheep) was used to characterize both the electrical activity and the calcium signaling of three distinct left atrium regions (appendage, free wall and pulmonary veins) in control conditions and after acetylcholine perfusion (5 μM) to induce acute atrial fibrillation. High-resolution dual calcium-voltage optical mapping on the left atria of sheep was performed to explore the spatiotemporal dynamics of calcium signaling in relation to electrophysiological properties.
Results:
Action potential duration (at 80% repolarization) was not significantly different in the three regions of interest for the three pacing sites. In contrast, the time to 50% calcium transient decay was significantly different depending on the region paced and recorded. Acetylcholine perfusion and burst pacing-induced atrial fibrillation when pulmonary veins and appendage regions were paced but not when the free wall region was. Dantrolene (a ryanodine receptor blocker) did not reduce atrial fibrillation susceptibility.
Conclusion:
These data provide the first evidence of heterogenous calcium signaling across the healthy left atrium. Such basal regional differences may be exacerbated during the progression of atrial fibrillation and thus play a crucial role in focal arrhythmia initiation without ryanodine receptor gating modification.
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