There is mounting evidence that major health problems like hypertension, heart disease, atrial fibrillation, heart failure, stroke, and renal falure are caused by overactive sympathetic nerves. However, there is no diagnostic device available to measure sympathetic nerve activity (SNA) or establish over activity thresholds for illness that require treatment. Measures like plasma norepinephrine (NE) levels, plasma NE spillover levels, heart rate variability and muscle sympathetic nerve activity (MSNA) are used to quantify SNA in experimental settings. The recent Simplicity HTN-3 study failed to show clinical efficacy in reducing hypertension primarily because of incomplete denervation due to the lack of in-situ feedback to the physician from renal sympathetic nerve activity (RSNA) during the procedure. Accordingly, there is a significant need for developing new methods for clinically recording SNA and at different target sites to monitor disease progression and establish thresholds for preventative treatment. In this proposal, we address this need by developing a device to monitor RSNA. Our previous studies demonstrated the feasibility of a local drug delivery catheter to inject a neurotropic drug and selectively induce degenerative changes in renal nerves and reduce RSNA. We plan to incorporate a microelectrode in this device to monitor changes in RSNA during nerve block achieved by the neurotropic drug. Success with this novel device could enhance our understanding on RSNA and provide a procedural tool for monitoring RSNA during device-based treatment of hypertension and other chronic diseases mediated by the sympathetic nervous system. New devices and methods could be designed for diagnosing other diseases by measuring SNA near their respective target-organ sites. Ultimately, the proposal develops a method to quantify overactive SNA in the progression of chronic diseases and could significantly improve public health by early preventative treatment. .
Public Health Relevance Statement: Public Health Relevance: Major health problems like hypertension, heart disease, atrial fibrillation, heart failure, stroke, and kidney failure are associated with overactive sympathetic nerves. However, there is no clinical device available to measure sympathetic nerve activity (SNA) or establish over activity thresholds for illness, which require treatment. In this proposal, we examine the feasibility of developing a novel device to measure renal sympathetic nerve activity (RSNA). We expect the research work will lead to the development of a standard clinical test for measuring sympathetic over activity in humans, help establish limits on healthy vs. unhealthy renal nerve activity levels in hypertensive, heart failure and chronic renal failure patients. In addition, proposal will enable the development of a RSNA device to provide real-time feedback to clinicians performing renal denervation procedures to treat sympathetic hypertension. Success of this proposal will enable the development of new devices and therapies to treat chronic diseases and target organs mediated by the sympathetic nervous system.
Project Terms: Accelerometer; Address; Adolescent; American; Anatomy; Animal Model; animal tissue; Area; Atrial Fibrillation; base; Biological Assay; Catheters; Chronic Disease; Chronic Kidney Failure; Clinical; clinical efficacy; Clinical Research; Communities; Denervation; design; Development; Device or Instrument Development; Devices; diagnosis design; Diagnostic; Disease; Disease Progression; effective therapy; electrical measurement; Electrodes; Electronics; Failure; Family suidae; Feedback; Future; Goals; Health; Heart failure; heart rate variability; Human; Hypertension; hypertension treatment; hypertensive heart disease; improved; In Situ; Injection of therapeutic agent; instrumentation; Investigation; Kidney; Kidney Failure; Lead; local drug delivery; Measurement; Measures; Mediating; Methods; Microelectrodes; model development; Modeling; Monitor; monitoring device; Muscle; National Heart, Lung, and Blood Institute; Nerve; Nerve Block; neuropharmacologic agent; neurotransmission; Norepinephrine; novel; Organ; Patients; Pharmaceutical Preparations; Phase; Physicians; Physiology; Plasma; pre-clinical; Pre-Clinical Model; Pressoreceptors; Preventive treatment; Procedures; Public Health; public health relevance; Rattus; renal artery; Research; research clinical testing; Resistant Hypertension; sciatic nerve; sensor; Signal Transduction; Site; Societies; stroke; success; Sympathetic Nervous System; System; Testing; Time; tool; Training; Tungsten; United States Food and Drug Administration; Work
