title: Pulmonary artery denervation reduces pulmonary artery pressure and induces histological changes in an acute porcine model of pulmonary hypertension.
abstract: BACKGROUND
  Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level.
  
  
  RESULTS
  Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters.
  
  
  CONCLUSIONS
  Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety.
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.). a.rothman@sheffield.ac.uk.
authors.forename: Alexander M K
authors.initials: AM
authors.lastname: Rothman
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Nadine D
authors.initials: ND
authors.lastname: Arnold
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Oliver
authors.initials: O
authors.lastname: Watson
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Swift
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Robin
authors.initials: R
authors.lastname: Condliffe
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Charlie A
authors.initials: CA
authors.lastname: Elliot
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: David G
authors.initials: DG
authors.lastname: Kiely
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: S Kim
authors.initials: SK
authors.lastname: Suvarna
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Julian
authors.initials: J
authors.lastname: Gunn
authors.affiliation: From the Department of Cardiovascular Science (A.M.K.R., N.D.A., O.W., S.K.S., J.G., A.L.), Academic Unit of Radiology (A.J.S.), and INSIGNEO, Institute for Insilico Medicine (A.M.K.R., A.J.S., J.G.), University of Sheffield, Sheffield, United Kingdom; Medtronic Inc, Santa Rosa, CA (W.C.); and Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom (R.C., C.A.E., D.G.K.).
authors.forename: Allan
authors.initials: A
authors.lastname: Lawrie
mesh_terms: D000208:Acute Disease; D000818:Animals; D017776:Autonomic Pathways / Q000378:metabolism / Q000601:surgery*; D001794:Blood Pressure; D002302:Cardiac Output; D017115:Catheter Ablation; D003714:Denervation; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000628:therapy*; D011651:Pulmonary Artery / Q000294:innervation / Q000473:pathology / Q000601:surgery*; D013552:Swine; D014655:Vascular Resistance; D014661:Vasoconstriction
keywords: ablation techniques; hypertension; nervous system; pulmonary; pulmonary artery; pulmonary circulation