Electroanatomical exploration of pulmonary veins sleeve myocardium in the development of atrial fibrillation in ageing and hypertension

In mammals, the complex anatomical structure connecting pulmonary veins (PVs) with the posterior wall of the left atrium (LA) of the heart, defined as LA-PV junction, is a source of electrical ectopic pulses, which initiate and maintain atrial fibrillation (AF), the most prominent sustained arrhythmia that worsens with tissue remodelling due to ageing and hypertension.

PVs resident cardiomyocytes generate electrical pulses contributing to arrhythmogenesis within the LA-PV junction.

Moreover, PV myocardium expresses atrial-specific small conductance calcium-activated potassium (SK) channels, which are involved in AF.

Although PVs ectopy is pivotal in AF onset, the pathophysiological space-time dynamic of PV cardiomyocytes intermittent firing and the proarrhythmic role of SK-channels in the LA-PV junction have not been investigated in ageing and hypertension.

Aim of this project is to define and quantify, for the first time, the intermittent arrhythmogenic pattern of pulses generated by PV cardiomyocytes when challenged by SK-channels antagonists in young adult and aged spontaneously hypertensive rats compared to age-matched healthy rats.

Moreover, the three-dimensional electrical heterogeneity of LA-PV spontaneous firing will be described by creating electro-anatomical high-density maps in the aforementioned experimental groups.

This project will generate critical knowledge about how LA-PV junction electrically dissociates from sinus rhythm during AF onset and will unveil the role of PVs SK-channels in the pathophysiology process of AF.

Moreover, this will allow me to acquire new skills to become a successful independent researcher in cardiovascular physiology and electrophysiology of cardiac arrhythmias.