Research Project
9045891
? DESCRIPTION (provided by applicant): 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. .
