{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:16:40Z","timestamp":1790705800376,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,4,4]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by\n            <jats:sup>123<\/jats:sup>\n            I-MIBG\u2013single-photon emission computed tomography.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014This study investigated neuronal reuptake of norepinephrine (uptake-1) and \u03b2-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects. All subjects underwent positron emission tomography with the volume of distribution (V\n            <jats:sub>d<\/jats:sub>\n            ) of [\n            <jats:sup>11<\/jats:sup>\n            C]hydroxyephedrine (\n            <jats:sup>11<\/jats:sup>\n            C-HED) used to assess presynaptic norepinephrine reuptake, the maximum binding capacity (B\n            <jats:sub>max<\/jats:sub>\n            ) of [\n            <jats:sup>11<\/jats:sup>\n            C]CGP-12177 (\n            <jats:sup>11<\/jats:sup>\n            C-CGP-12177) to assess postsynaptic \u03b2-adrenergic receptor density, and [\n            <jats:sup>15<\/jats:sup>\n            O]H\n            <jats:sub>2<\/jats:sub>\n            O for quantification of myocardial blood flow. Patients with ARVC demonstrated a highly significant global reduction in postsynaptic \u03b2-adrenergic receptor density compared with that in control subjects (B\n            <jats:sub>max<\/jats:sub>\n            of\n            <jats:sup>11<\/jats:sup>\n            C-CGP-12177: 5.9\u00b11.3 vs 10.2\u00b12.9 pmol\/g tissue,\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0007), whereas the presynaptic uptake-1 tended toward reduction only (V\n            <jats:sub>d<\/jats:sub>\n            of\n            <jats:sup>11<\/jats:sup>\n            C-HED: 59.1\u00b125.2 vs 71.0\u00b118.8 mL\/g tissue, NS). There were no differences in myocardial blood flow between the groups, and plasma norepinephrine was within normal limits in patients and control subjects.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The findings demonstrate a significant reduction of myocardial \u03b2-adrenergic receptor density in patients with ARVC. This may result from a secondary downregulation after increased local synaptic norepinephrine levels caused by increased firing rates of the efferent neurons or as the result of impaired presynaptic catecholamine reuptake. These findings give new insights into the pathophysiology of arrhythmogenesis in ARVC, with potential impact on diagnostic evaluation and therapeutic management.\n          <\/jats:p>","DOI":"10.1161\/01.cir.101.13.1552","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"1552-1558","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":116,"title":["Abnormalities of Cardiac Sympathetic Innervation in Arrhythmogenic Right Ventricular Cardiomyopathy"],"prefix":"10.1161","volume":"101","author":[{"given":"Thomas","family":"Wichter","sequence":"first","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scha\u0308fers","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher G.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Borggrefe","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Lerch","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A.","family":"Lammertsma","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Hermansen","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otmar","family":"Schober","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu\u0308nter","family":"Breithardt","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial College School of Medicine, Hammersmith Hospital (C.G.R., A.A.L, F.H., P.G.C.), London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo G.","family":"Camici","sequence":"additional","affiliation":[{"name":"From the Hospital of the Westfa\u0308lische Wilhelms-University, Department of Cardiology and Angiology and Institute for Arteriosclerosis Research (T.W., M.B., G.B.) and Department of Nuclear Medicine (MS, H.L., O.S.), Mu\u0308nster, Germany, and the Medical Research Council-Cyclotron Unit and Imperial 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