Minimally Invasive Cardio-Pulmonary Plexus Block for the Treatment of Pulmonary Hypertension

Project Summary Pulmonary hypertensionPHis a devastating disease of the pulmonary vasculature characterized by high blood pressure in the pulmonary arteriesCurrent therapies to treat PH have significant limitations and substantial costsCurrently there are approved therapies serving less thanof patients with PHIn contrast to the intense therapeutic focus on local pulmonary vasoactive mediatorsrelatively limited attention has been directed towards the important role played by the autonomic nervous system in PHSympathetic over activity plays a critical role in PH and recent studies have highlighted the role of invasive sympathetic denervation in management of pulmonary hypertensionRecentlya novel approach to localize pulmonary vascular sympathetic blockade has emergedpulmonary artery denervationPADNwhich blocks the sympathetic efferent component of the pulmonary reflexvasoconstrictionby ablation of the nerves immediately adjacent to the pulmonary artery using an intravascular catheter equipped with ablation elementsPreliminary clinical trials of PADN have shown that it effective in reducing pulmonary pressuresleading to sustained improvement in sixminute walk test distance and tricuspid excursionKey limitations to the currently available method of PADN include its invasive naturepotential for PA injuryand need for specialized equipment expertiseOur proposal will prove the feasibility of a completely newminimally invasive bronchoscopic method to reduce sympathetic signaling to the pulmonary vasculature for the treatment of PHOur approach is a novel in that we are able to exploit the anatomy of the cardio pulmonary nerves to achieve substantial bilateral sympathetic denervation and reduce pulmonary pressures at a single site in front of the tracheal bifurcation known as the cardio pulmonary plexusWe can access this region using techniques known to interventional pulmonologistsThis project will be completed in several sequential stagesFor this Phase I SBIR we will demonstrate proof of physiological and technical concept in a well established canine model of PHIn this modelwe will demonstrate that block of the cardio pulmonary plexus in the pretracheal region significantly reduces the response to electrical stimulation of bilateral stellate ganglia and is safeeffective at reducing pulmonary pressuresSuccessful completion of the specific aims will lead to development lead to development of a clinical grade device to safely and effectively denervate the cardio pulmonary plexusplanned for Phase II of the projectSympathetic over activity is uniformly associated with poor survival in PHThis work will validate a new method for interrupting sympathetic signaling to the pulmonary plexus that we believe will ultimately become the first line therapy for many patients suffering from PH Public Health Relevance Pulmonary hypertension is disease of complex etiology that results in significant morbidity and mortalityCurrent management of pulmonary hypertension is palliativeand for most patients there are no treatment optionsCommon among the many forms of pulmonary hypertension is the important role of the sympathetic nervous systemThis proposal will validate a newminimally invasive method for selective pulmonary sympathetic blockade that can be performed in the interventional labsWe believe this will prove to be an important therapeutic option for many patients with pulmonary hypertension whose needs are unmet by modern medicine