Published Online
on November 1, 2004

A more recent version of this article appeared on November 9, 2004

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Submitted on May 28, 2003
Revised on April 1, 2004
Accepted on April 20, 2004

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, and 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.

^* To whom correspondence should be addressed. E-mail: kies{at}uni-muenster.de.

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 -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 -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 -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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