title: Abnormal myocardial presynaptic norepinephrine recycling in patients with Brugada syndrome.
abstract: BACKGROUND
  Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome.
  
  
  RESULTS
  Nine patients with Brugada syndrome (6 male, 3 female; age, 41+/-13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11C-Hydroxyephedrine (11C-HED) and the nonselective beta-blocker 11C-CGP 12177 (11C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9+/-16.2 mL/g versus 69.1+/-14.2 mL/g; P<0.05), whereas postsynaptic beta-adrenoceptor density, assessed by 11C-CGP, was similar in patients and control subjects (10.4+/-6.7 pmol/g versus 10.2+/-2.9 pmol/g; P=NS).
  
  
  CONCLUSIONS
  The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved beta-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.
authors.affiliation: Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Str 33, D-48149 Münster, Germany. kies@uni-muenster.de
authors.forename: Peter
authors.initials: P
authors.lastname: Kies
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichter
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.forename: Matthias
authors.initials: M
authors.lastname: Paul
authors.forename: Klaus P
authors.initials: KP
authors.lastname: Schäfers
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
authors.forename: Lars
authors.initials: L
authors.lastname: Stegger
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: Ornella
authors.initials: O
authors.lastname: Rimoldi
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
authors.forename: Otmar
authors.initials: O
authors.lastname: Schober
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000328:Adult; D001692:Biological Transport; D002250:Carbon Radioisotopes; D004809:Ephedrine / Q000031:analogs & derivatives*; D005260:Female; D006321:Heart / Q000294:innervation*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017729:Presynaptic Terminals / Q000378:metabolism*; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013577:Syndrome; D017180:Tachycardia, Ventricular / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D002250:Carbon Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D017661:Receptors, Presynaptic; C065363:3-hydroxyephedrine; D004809:Ephedrine; C033394:CGP 12177; D009638:Norepinephrine