Acute modulation and chronic remodelling of intrinsic cardiac nervous system properties during myocardial ischemia, atrial tachyarrhythmias, and spinal cord stimulation.

Cardiac arrhythmias, which include heart beat irregularities and excessively rapid or slow heart rate, are major causes of cardiac morbidity and mortality. In particular, atrial fibrillation is the most common arrhythmia in adults and its prevalence increases with ageing. It has been suggested that targeting cardiac nerves, in addition to cardiac muscle, might allow interventional cardiologists and surgeons to improve the effectiveness of ablation therapy, particularly to reduce the risk of arrhythmia recurrence. The 'intrinsic' cardiac neurons form about 6 cellular aggregates called 'ganglionated plexuses' that are nested in fatty tissues at specific locations on the surface of the heart. Herein, we hypothesize that the activity of the intrinsic cardiac nervous system is enhanced in cardiac pathologies such as cardiac arrhhythmias and coronary artery disease, leading to further exacerbation of the disease, and that the system can be stabilized by stimulation of the upper thoracic segments of the spinal cord. In fact, spinal cord stimulation via chronically implanted electrodes is in clinical use, especially in Europe, for the treatment of symptomatic coronary artery disease refractory to pharmacological and surgical therapy, but the mechanism of this therapy is not known. The general objective of the proposed research is to elucidate the mechanisms for therapeutic modulation of the intrinsic cardiac nervous system. These clinically-relevant issues will be investigated in canine models of atrial fibrillation and coronary artery disease using elctrocardiographic recording in situ and intracellular recording of neuronal activity in vitro. Corroborative data will be obtained in a pilot study of the properties of intrinsic cardiac neurons contained in atrial fatty tissues collected from patients undergoing coronary artery bypass surgery.