Pathophysiology of cardiac innervation: Brainstem and intrinsic cardiac nervous system

INTRODUCTION: We have proposed that the nerve cells on the heart are like a 'little brain on the heart' ie, the intrinsic cardiac nervous system. These cells acting as the final regulator of normal cardiac function and when they do not function properly in patients with cardiac disease the consequences may be devastating. We have recently identified striking pathological changes in intrinsic cardiac neurons of humans with ischemic heart disease. We are proposing to determine the conditions causing degenerative changes and whether these are changes related to aging and/or Alzheimer's disease. PROPOSED STUDIES: 1) Myocardial ischemia: To determine the pathological changes that human intrinsic cardiac ganglia undergo in the presence of documented coronary artery disease associated with myocardial ischemia. 2) Heart failure: To characterize the pathological changes that such neurons undergo during the evolution of heart failure in animal models. 3) Aging and Alzheimer's disease: To determine any pathological changes in intrinsic cardiac neurons related to aging and Alzheimer's disease. SIGNIFICANCE: Our preliminary findings indicate that intrinsic cardiac neurons undergo pathological changes on human hearts with a comprised blood supply. If intrinsic cardiac neurons are adversely affected by such agents or by focal ventricular ischemia, then novel therapeutic strategies will have to be developed to modify the final common regulator or cardiac function in the management of cardiac disease states.