The cardiac neuronal hierarchy is made up of interdependent feedback loops comprising somata located in i) intrinsic cardiac ganglia, ii) intrathoracic extracardiac (stellate, middle cervical) as well as iii) the spinal cord, iv) brainstm and v) higher centers (up to the insular cortex). Each of these processing center contains afferent, efferent and interactive (local circuit ones in peripheral ganglia) neurons which interac locally and in an interdependent fashion with other levels to coordinate regional cardiac indices on a beat-to-beat basis. It is now recognized that autonomic dysregulation is central to the evolution of heart failure and arrhythmias. With respect to heart disease and the cardiac nervous system, there is an upregulation of the sympathetic nervous system and a corresponding decrease in parasympathetic activity. Many of these changes are driven by alterations in afferent transduction and processing of that information at multiple levels of the cardiac nervous system. There is little understanding of how such neural systems adapt during disease progression. There are two critical unmet needs in the field of cardio-neural mapping: 1) Development and optimization of 2D and 3D electrode arrays for chronic, high-fidelity neural recording from peripheral ganglia and 2) Integration of neural recordings with chronic high-fidelity recording of cardiac electrophysiological function. To address this need three aims are proposed.
Specific aim 1 : To develop 2D and 3D microelectrode arrays and systems for chronic, high-fidelity neural recording from intrinsic cardiac ganglia. Proposed methods include development of thin-film based flexible microelectrode arrays with up to 256 electrode contacts. Once proof of concept is established in the acute setting, chronic packages and fixation techniques will be developed to enable chronic recordings from large animal models.
Specific aim 2 : To develop 3D electrode arrays and systems for chronic, high-fidelity neural recording in peripheral encapsulated sympathetic (stellate) and sensory (nodose) ganglia. Proposed methods include development of thin-film based 3D penetrating microelectrode arrays (up to 256 electrode contacts). Once proof of concept is established in the acute setting, chronic packages and fixation techniques will be developed to enable chronic recordings from encapsulated peripheral ganglia from large animal models.
Specific aim 3 : To develop conformal high-definition grid electrodes for chronic, high-resolution electrophysiological mapping from atrial and ventricular epicardial surfaces. These `HD grid electrodes' will have up to 512 sites. Similar to and in conjunction with Aims 1 and 2, chronic packages and fixation techniques will be developed to enable chronic high-fidelity cardiac-neural mapping for up to 28 days. New Knowledge and Innovation: Creation of a distributed electrode system for chronic and continuous high fidelity cardio-neural mapping in normal and pathological states.
Interactions between central and peripheral aspects of the cardiac nervous system play a major role in control of the normal and diseased heart; imbalances within this system are associated with deleterious effects including abnormal heart beats, sudden cardiac death (SCD) and heart failure. However, there is little understanding of how such neural systems adapt during progression of cardiac disease. To address this unmet need the primary focus of this proposal is to: 1) Development implantable electrode arrays that allow for chronic, high-fidelity 3D neural recording from peripheral autonomic and sensory ganglia and 2) to then interlace such neural recording with chronic high-fidelity recording of cardiac electrical activity.
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