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YIA3 Regional Action Potential Gradients in the Murine Left Atrium
  1. Andrew Holmes,
  2. Ting-Yue Yu,
  3. Stefan Kuhlman,
  4. Fahima Syeda,
  5. Larissa Fabritz,
  6. Paulus Kirchhof
  1. University of Birmingham

Abstract

Background Regional differences in action potential (AP) morphology in the adult left atrium (LA) may account for susceptibility to atrial fibrillation. The posterior LA wall close to the junction with the pulmonary veins (LA-PV) is an important area contributing to initiation and maintenance of atrial fibrillation. The posterior LA has a distinct embryologic origin: Its development is regulated by PITX2, a gene that has been inflicted in the genetic predisposition to AF. So far, it is not known whether the electrophysiology of the posterior LA differs from that of other parts of the LA. We therefore characterised the electrical phenotype of the LA-PV compared to other LA regions.

Methods Transmembrane (TAPs) and optical (OAPs) action potentials were recorded from 20 superfused murine LA taken from 12 male and 8 female mice aged 12–20 W, bred on an MF1 background. Optical high-density AP mapping was performed and optical APs were recorded from 9 regions across the LA using a dedicated murine activation system (Hamamatsu ORCA flash 4, Di-4-Anepps, sampling rate 1–2 kHz). OAPs were analysed using custom made algorithms produced in MATLAB. At each cycle length, 25 action potentials were averaged to generate a mean waveform that was then used for analysis. TAPs were recorded from 3 LA regions: 1) the posterior LA towards the junction with the pulmonary vein (LA-PV), 2) the medial dome (LA-M) and 3) the LA lateral wall (LA-LW). All Preparations were paced at 100ms.

Results OAP distribution maps (n = 8 LA) identified a LA-PV to LA-LW pattern of APD shortening and also demonstrated that there is relatively high local APD heterogeneity within the LA-PV region. TAP recordings identified a higher action potential amplitude (APA) in the LA-PV (84 ± 2 mV) than LA-M (78 ± 1 mV, p < 0.05) and LA-LW (77 ± 2 mV, n = 12 LA, p < 0.05). Vmax was greater in the LA-PV (132 ± 10 V/s) than the LA-LW (109 ± 5 V/s, p < 0.05). The resting membrane potential was not different between regions. TAPs were prolonged in the LA-PV compared with the other 2 regions; APD90 LA-PV 28 ± 2 ms, LA-M 21 ± 0.7 ms, LA-LW 19 ± 1 ms, p < 0.05, Figure 1. In addition, APD70 in the LA-LW (11 ± 0.4 ms) was shorter than the LA-M (9 ± 0.4 ms, p < 0.05) suggestive of a more continuous intra-atrial APD gradient. Conduction velocities in different regions will be reported.

Abstract YIA3 Figure 1

Regional action potential duration variability in the murine left atrium

Conclusion Regional AP differences in the murine LA clearly suggest that the posterior left atrium has a distinct electrophysiological profile which may render this region susceptible to the genesis and maintenance of AF. Prolonged APD and higher AP amplitude suggest a role as a driver of electrical LA activity. Further studies are warranted to determine whether PITX2 is important for the maintenance of these electrophysiological differences.

  • Atrial Fibrillation
  • Action Potential Heterogeneity
  • PITX2

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