CORDIS3D · Cardiac Origin of Rhythm DISturbances: 3-Dimensional structural investigations

Myocardial structure is important in the triggering and maintenance of many cardiac arrhythmias including atrial and ventricular fibrillation. Detailed knowledge of myocardial structure is essential to the understanding of these disorders and in the development of diagnostic and therapeutic strategies. This must include the normal and pathological distribution of key functional proteins such as connexins. There are a variety of structural imaging methodologies which can be used to study normal and pathological hearts: high spatial resolution MRI and CT, Diffusion Tensor MRI, three-dimensional volume histology from sections or from tissue block imaging. Furthermore, histological imaging can determine molecular distributions after labelling, which may be by immunohistochemistry, viral transfection or transgenics. In this exchange partnership we will bring together four leading centres with unique and complementary expertise in order to systematically study the structural substrate of propagation and arrhythmia in the normal and failing heart and in heart failure. Arrhythmias studied will be the role of Purkinje Fibres in ventricular fibrillation, pulmonary venous cuff re-entry in atrial fibrillation, the role of structural changes in myocardial infarction in ventricular fibrillation and right ventricular outflow tract ventricular tachycardia. Tissue studied will include hearts from relevant animal disease models, post-mortem/operative human tissues. Disease models studied will include small and large animal (rat/sheep & pig) models of infarction and right heart failure. Rat models have the advantage that the small cardiac size allows high spatial resolution imaging to be carried out of the whole cardiac volume, while the large animal models have structure and electrophysiology generally closer to man. Structural imaging will be accompanied by 3D-electrophysiological recording and computational modelling to enable investigation of the structure function relationship.