Conduction and innervation in the healthy and diseased heart

Abstract

Cardiovascular disease is the leading cause of death worldwide. About half of these deaths are sudden cardiac deaths of which ventricular arrhythmias are an important cause. Different types of ventricular arrhythmias are recognized, depending on their underlying cause and mechanism. The ventricular conduction system consists of a network of specialized cells called Purkinje fibres, which are responsible for fast and synchronous electrical activation of the ventricles. Many types of ventricular arrhythmias, including ventricular fibrillation, are known to be initiated by the Purkinje network. The cardiac sympathetic nervous system is responsible for evoking the fight-or-flight response, and influences nearly all functional aspects of the heart, including its electrical activity. Various cardiac diseases, including myocardial infarction, are associated with cardiac sympathetic hyperactivity which disrupts normal cardiac function and increases the risk of ventricular arrhythmias. The right ventricular outflow tract constitutes the outlet of the right ventricle, and is a preferential site of origin of various types of ventricular arrhythmias including those in the Brugada syndrome or in absence of structural heart disease. The research described in this thesis investigates markers that could explain risk of various types of life-threatening ventricular arrhythmias, which could be valuable for effective prevention of sudden cardiac death.