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(Circulation. 2004;110:3017-3022.)
© 2004 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

Peter Kies, MD; Thomas Wichter, MD, FESC; Michael Schäfers, MD; Matthias Paul, MD; Klaus P. Schäfers, PhD; Lars Eckardt, MD; Lars Stegger, MD; Eric Schulze-Bahr, MD; Ornella Rimoldi, MD; Günter Breithardt, MD, FESC; Otmar Schober, MD, PhD, FESC; Paolo G. Camici, MD, FESC, FRCP

From the Department of Nuclear Medicine (P.K., M.S., K.P.S., L.S., O.S.) and the Department of Cardiology and Angiology (T.W., M.P., L.E., E.S.-B., G.B.), University Hospital of Münster, Münster, Germany; the Institute for Arteriosclerosis Research at the University of Münster (T.W., M.S., L.E., E.S.-B., G.B.), Münster, Germany; and MRC Clinical Sciences Centre (P.K., L.S., O.R., P.G.C.), Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.

Correspondence to Peter Kies, MD, Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Str 33, D-48149 Münster, Germany. E-mail kies{at}uni-muenster.de

Received May 28, 2003; de novo received December 29, 2003; revision received April 1, 2004; accepted April 20, 2004.

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.

Methods and 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 ß-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 ß-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 ß-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.

Key Words: fibrillation • death, sudden • nervous system, autonomic • receptors, adrenergic, beta

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