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Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia

Michael Schäfers, MD^* , Hartmut Lerch, MD^*, Thomas Wichter, MD^*, Christopher G. Rhodes, MSc, Adriaan A. Lammertsma, PhD, Martin Borggrefe, MD^*, Flemming Hermansen, MD, Otmar Schober, MD, PhD^*, G.ünter Breithardt, MD, FESC, FACC^* and Paolo G. Camici, MD, FESC, FACC, FRCP

^* Department of Nuclear Medicine and Department of Cardiology and Angiology and Institute for Arteriosclerosis Research, Westfälische Wilhelms University, Munster, Germany
Medical Research Council–Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital, London, England, United Kingdom

View larger version (18K): [in a new window]   Figure 1 Scheme of presynaptic and postsynaptic sympathetic innervation. The norepinephrine (NE) analogue [11C]HED was used for measuring presynaptic reuptake of norepinephrine (UP), and the nonselective beta-blocker [11C]CGP 12177 was used for measuring postsynaptic beta-adrenoceptor (ß-AR) density.

View larger version (17K): [in a new window]   Figure 2 Norepinephrine reuptake measured by Vd of [11C]HED in patients with RVO-VT and control subjects (mean value is indicated by horizontal lines).

View larger version (16K): [in a new window]   Figure 3 Bmax for beta-adrenoceptors measured using [11C]CGP 12177 in patients with RVO-VT and control subjects (mean value is indicated by horizontal lines).

View larger version (20K): [in a new window]   Figure 4 Hypothetic pathophysiologic mechanism of tachycardia in patients with idiopathic RVO-VT. Reduced reuptake (UP) of norepinephrine (NE) into the nerve terminal or increased release (RE) into the synaptic cleft leads to an increase in local norepinephrine concentration in the synaptic cleft and stimulation of postsynaptic beta-adrenoceptors (ß-AR). In turn this leads to increased cyclic adenosine monophosphate (cAMP) through activation of the stimulatory G protein (GS) and adenylyl cyclase (AC). The increase in cAMP will produce a rise in intracellular Ca2+ levels by activation of protein kinase A (PKA) and will eventually trigger ventricular tachycardia. That this occurs despite beta-adrenoceptor downregulation suggests that norepinephrine is still capable of significantly increasing intracellular cAMP concentration, probably due to changes in the beta-adrenoceptor–G-protein–adenylyl cyclase pathway.