The intrinsic cardiac nervous system: experimental study of novel therapies for disturbances of cardiac rhythm and function

Together with our group of international collaborators, we have proposed that nervous control of the heart is distributed along a system of intrathoracic and intrinsic cardiac ganglia (little brain on the heart) that function in relation with central neurons in the brain and spinal cord. Moreover, disturbances of this system can generate cardiac arrhythmias and exacerbate myocardial ischemia and failure in experimental models of coronary artery disease. Our request for funding is based on the proposition that the activity of the intrathoracic and intrinsic cardiac neurons can be stabilized in heart disease by activation of central neurons via electrodes implanted at specific locations in the spinal cord (as already implemented clinically in novel forms of therapy for refractory angina pectoris). Building on this new knowledge, the proposal presented herein is to investigate the neuromodulatory mechanisms whereby spinal cord stimulation exerts a protective action in animal models of cardiac arrhythmias and heart failure. This will be done using sophisticated experimental mapping methodologies in vivo and extracting neurons from the intrinsic cardiac nervous system to investigate the actions of putative neuromediators in vitro. The proposed studies will generate new information supporting the clinical use of such novel therapies.