Electrophysiological differences in atria and ventricles

Kabir, Syeeda Nashitha (2024). Electrophysiological differences in atria and ventricles. University of Birmingham. Ph.D.

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Abstract

Atrial fibrillation (AF) is the most common arrhythmia, affecting over 1% of the population. Sodium channel blockers are commonly used to treat AF by restoring sinus rhythm. Current anti-arrhythmic drugs such as flecainide, do not specifically target atrial sodium channels, and information on electrophysiological differences between atria and ventricles is limited. Furthermore, flecainide is contraindicated in ischaemic heart disease (IHD) patients due to increased mortality. The mechanisms are unknown, necessitating further study. Understanding electrical differences and drug sensitivities is vital for effective treatment and improved patient outcomes.

The project aimed to characterise electrophysiological properties in left atria (LA) and left ventricles (LV), distinguish the differential effects of flecainide, in LA and LV, and investigate interaction of flecainide and ischaemia. Electrical activity from ex vivo hearts were measured using optical mapping from healthy wildtype (WT) mice aged 10 to 15 weeks. Global ischaemia was triggered using low perfusion pressure method, and regional ischaemia was triggered by ligating left anterior descending artery (LAD) ex vivo.

Our data showed a significantly slower conduction and shorter action potential duration (APD) in the LA compared to LV. Flecainide showed inhibition of the sodium current and slowed conduction to a greater degree in the LA compared to LV. CV was further slowed in ischaemic hearts in the presence of flecainide. Ischaemia prolonged the APD when compared to baseline APD. Further investigation of molecular drivers of the atrial and ventricular resting membrane potential (RMP) and the molecular interaction partners of flecainide may help to identify new targets for early rhythm control therapy in patients with AF.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):