"Sudden cardiac death (SCD) following ventricular fibrillation (VF) is a major cause of mortality in the industrialised world. VF is characterised by chaotic electrical activity in the ventricles leading to severe cardiac dysfunction. Thus far, the underlying mechanisms for the initiation and maintenance of VF are not fully understood. Recent clinical developments in the treatment of VF by the Host’s laboratory have discovered distinct electrical activity associated with a specialised cell-type, Purkinje fibres, which were found to precede the spontaneous beats that manifest VF. Targeted radiofrequency (RF) ablation of these sources has markedly improved treatment and the rates of recurrence of arrhythmias in patients suffering from idiopathic VF. There is also growing evidence that the Purkinje system may be involved in arrhythmogenesis in cardiac pathologies such as myocardial infarction. Therefore, this proposal aims to utilise in vivo electrophysiological techniques in combination with a newly developed ex vivo optical imaging technique on a large animal model (sheep) to determine the roles of Purkinje fibres in the development of life-threatening arrhythmias with a focus on improving the effectiveness of ablation therapies. Furthermore, this approach shall be applied to further investigate a cardiac disease model that is at significant risk of arrhythmogenesis, myocardial infarction. The proposed aims shall be carried out in vivo using MRI and epicardial and endocardial electrophysiological recordings. This will be followed by optical mapping of ex vivo coronary-perfused ventricular preparations providing insight into the 3D organisation of electrical activity. These techniques will provide the appropriate tools for determining the precise location of arrhythmogenic sources, the organisation of arrhythmias and the roles of Purkinje fibres. Successful completion of these research goals will have an important impact on future therapies for sudden cardiac death."