Chronic intermittent hypoxia (CIH), the hallmark of sleep-disordered breathing (SDB), induces many cardiovascular disorders as seen in SDB. Thus, CIH-exposed animals have been used as an effective model to study the neural mechanisms underlying SDB-induced cardiovascular dysfunctions. The prevailing hypothesis is that CIH unbalances autonomic control that leads to cardiovascular complications. However, the neural mechanisms underlying CIH-induced autonomic imbalance is poorly understood, which impedes the development of effective treatments. Our long-term goals are to understand the autonomic innervations' topographical organization within the heart and then to determine CIH-induced structural remodeling of this topographical innervation and functional imbalance of the autonomic control of the cardiovascular system. Since the autonomic interaction may occur in local cardiac circuitry, the objective of this proposal is to address six important questions using a combination of state-of-the art anatomical and physiological techniques:1) What is the topographical organization map of sympathetic innervation of the normal heart? 2) What is the topographical organization map of parasympathetic intrinsic cardiac ganglia (ICG) innervation of the normal heart? 3) How do sympathetic and parasympathetic nerves interact? The remaining questions can be addressed after we have answered the first three questions from the normal animals. These additional questions are: 4) Does CIH change sympathetic cardiac innervation and function? 5) Does CIH change ICG innervation and function? 6) Does CIH change sympathetic inhibition of parasympathetic control at the heart? Though effects of CIH on the central control have been extensively studied, CIH-induced autonomic peripheral changes have not been yet well defined. We hypothesize that CIH will remodel cardiac autonomic postganglionic innervation, as well as alter their functions and interaction in male and female mice. Specifically, in Aim 1, we will determine whether CIH will induce structural remodeling of sympathetic and ICG preganglionic neurons and their projections to cardiac targets.
In Aim 2, we will examine whether CIH will alter sympathetic postganglionic and parasympathetic ICG control of the heart and their functional interaction within the heart. Successful completion of these aims will provide novel information about the autonomic nerve topographical organization map within the whole heart, and the effects of CIH on the imbalance of autonomic control of the heart. The autonomic topographical organization in the 3D heart model will contribute to a cardiac-brain atlas and anatomical basis for normal autonomic cardiac functions. If CIH does have a significant effect on sympathetic and ICG innervation and function, we will further study the cellular and molecular mechanisms of how CIH may induce structural and functional deficits in the brain-heart circuitry, which will eventually contribute to new prevention and treatment strategies. These studies will enhance an integrated research and educational environment for biomedical sciences at UCF.
Chronic intermittent hypoxia (CIH), as seen in sleep-disordered breathing (SDB), induces cardiovascular disorders (e.g., hypertension, tachycardia, autonomic cardiac neuropathy and cardiac failure). CIH may alter the brain-heart connection which may lead to cardiovascular disorders. The goal of the present application is to understand the autonomic postganglionic innervation's topographical organization within the heart and then to determine CIH-induced structural remodeling of this topographical innervation and functional imbalance of autonomic control of the cardiovascular system.
