Optical mapping of Ca transient and voltage in left atria uncover critical links between Ca regional heterogeneity and atrial fibrillation susceptibility - 25/09/20
Résumé |
Introduction |
Atrial fibrillation (AF) is the most sustained form of arrhythmia in human population. Although electrophysiological and structural abnormalities are known to be involved in AF development, it has not been established whether cardiac remodelling, including calcium (Ca) signalling dysregulation, is homogenous throughout the different regions of the left atrium (LA). We hypothesised that differences across healthy LA may contribute to a unique, region-dependent Ca signalling and thus be involved in the pro-arrhythmic activity associated with electrical dysfunctions observed during AF.
Objective |
The study aimed to characterise, in a physiological relevant model (adult sheep), the electrical activity and the Ca signalling of 3 distinct LA regions (appendage, free wall and pulmonary veins), in control conditions and after acetylcholine perfusion (5μM, ACH) to induce acute AF.
Methods |
Sheep (n=16) were killed by pentobarbital overdose. Hearts were excised, LA separated and Langendorff-perfused after suturing leaky branches. Blebbistatin was used to eliminate motion artefact. Simultaneous Vm and intracellular Ca fluorescent signals were recorded with 2 CMOS cameras after loading preparations with RH237 and Rhod-2AM. LA were paced in the 3 LA regions and ECG was continuously recorded. In some experiments, ACH and burst pacing were used to trigger AF, with or without Dantrolene (a ryanodine receptor (RyR) blocker). Analysis was performed in all 3 regions.
Results |
Action potential duration (at 80% repolarization) was not significantly different in the 3 regions (for the 3 pacing areas). In contrast, time to 50% Ca transient decay was significantly different (depending of the region recorded and paced). ACH perfusion and burst pacing induced AF (8/16). Dantrolene did not reduce AF susceptibility.
Conclusion |
These data provide evidence that Ca regional heterogeneity in LA can play a crucial role in focal arrhythmia initiation, without RyR gating modification.
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Vol 12 - N° 2-4
P. 254 - octobre 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.