Functional Changes and Anatomical Remodeling of Brain-Heart Connection following Chronic Intermittent Hypoxia

Chronic intermittent hypoxia (CIH), as seen in sleep-disordered breathing (SDB), induces cardiovascular disorders (e.g., hypertension, cardiac neuropathy and cardiac failure). In particular, clinical studies have associated impairment of baroreflex sensitivity with heart failure. The prevailing hypothesis is that CIH (SDB) imbalances autonomic [sympathetic (Sym) and parasympathetic (PSym)] control of the cardiovascular system. However, the mechanism of CIH-induced autonomic imbalance is not well understood. Using a novel combination of anatomical, physiological and pharmacological techniques, we have demonstrated that CIH impairs baroreflex control of heart rate (HR) and induces dysfunction and structural reorganization of the PSym at multiple sites within the baroreflex circuitry (baroreceptor afferent, vagal cardiac motor neurons, and vagal efferent) in rats and mice. Peripherally, CIH increased aortic depressor nerve (ADN) function which is associated with pathological reorganization of its innervation on the wall of the aortic arch, including the disorganized, swollen afferent axons and terminals, and an enlarged receptive field. CIH enhanced HR responses to vagal efferent stimulation which is associated with the disorganized, swollen efferent axons and terminals, and increased synaptic connections with ganglionic neurons in the heart. Centrally, CIH reduced the number of cardiac vagal motor neurons (CVMNs) in the nucleus ambiguus (NA) of the brainstem immunoreactive for antibodies against AMPA and NMDA receptors and decreased HR responses to AMPA and NMDA injections into NA. Thus, our work has demonstrated that CIH alters the structure and function of multiple components within the baroreflex circuitry, which has provided a platform for the assessment of effectiveness of medical interventions.

Biography: Biography: Dr. Zixi Jack Cheng received his PhD of Psychology/Neuroscience from Purdue University. Dr. Cheng currently is an Associate Professor of Physiology at the University Of Central Florida College Of Medicine. His early research focused on Brain and Heart Connections. His recent work has been focused on effects of CIH and diabetes on autonomic control of the heart. He has published over 45 peer-reviewed papers and his research program has been previously funded by the National Institute of Health and American Heart Association.