{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:18:42Z","timestamp":1792657122045,"version":"4.5.0"},"reference-count":47,"publisher":"American Society for Clinical Investigation","issue":"11","funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["NIHDP2HL132356"],"award-info":[{"award-number":["NIHDP2HL132356"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"crossref","award":["OT2OD023848"],"award-info":[{"award-number":["OT2OD023848"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,4]]},"abstract":"<jats:p>\n                    The sympathetic nervous system plays an important role in the occurrence of ventricular tachycardia (VT). Many patients, however, experience VT despite maximal doses of beta blocker therapy, possibly due to the effects of sympathetic cotransmitters such as neuropeptide Y (NPY). The purpose of this study was to determine, in a porcine model, whether propranolol at doses higher than clinically recommended could block ventricular electrophysiological effects of sympathoexcitation via stellate ganglia stimulation, and if any residual effects are mediated by NPY. Greater release of cardiac NPY was observed at higher sympathetic stimulation frequencies (10 and 20 vs. 4 Hz). Despite treatment with even higher doses of propranolol (1.0 mg\/kg), electrophysiological effects of sympathetic stimulation remained, with residual shortening of activation recovery interval (ARI), a surrogate of action potential duration (APD). Adjuvant treatment with the NPY Y\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonist BIBO 3304, however, reduced these electrophysiological effects while augmenting inotropy. These data demonstrate that high-dose beta blocker therapy is insufficient to block electrophysiological effects of sympathoexcitation, and a portion of these electrical effects in vivo are mediated by NPY. Y\n                    <jats:sub>1<\/jats:sub>\n                    receptor blockade may represent a promising adjuvant therapy to beta-adrenergic receptor blockade.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.135519","type":"journal-article","created":{"date-parts":[[2020,6,9]],"date-time":"2020-06-09T08:24:50Z","timestamp":1591691090000},"source":"Crossref","is-referenced-by-count":45,"title":["Cardiac sympathetic activation circumvents high-dose beta blocker therapy in part through release of neuropeptide Y"],"prefix":"10.1172","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3762-9596","authenticated-orcid":true,"given":"Jonathan D.","family":"Hoang","sequence":"first","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"},{"name":"UCLA Molecular Cellular and Integrative Physiology Interdepartmental Program, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siamak","family":"Salavatian","sequence":"additional","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Amer","family":"Swid","sequence":"additional","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hamon","sequence":"additional","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marmar","family":"Vaseghi","sequence":"additional","affiliation":[{"name":"UCLA Cardiac Arrhythmia Center,"},{"name":"Neurocardiology Center for Excellence, and"},{"name":"UCLA Molecular Cellular and Integrative Physiology Interdepartmental Program, UCLA, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2008.01.003"},{"key":"B2"},{"issue":"12","key":"B3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41569-019-0221-2","article-title":"The autonomic nervous system and cardiac arrhythmias: current concepts and emerging therapies.","volume":"16","author":"Herring","year":"2019","journal-title":"Nat Rev Cardiol"},{"issue":"5 Pt 1","key":"B4","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1161\/01.CIR.78.5.1241","article-title":"Differential response to right and left ansae subclaviae stimulation of early afterdepolarizations and ventricular tachycardia induced by cesium in dogs","volume":"78","author":"Ben-David","year":"1988","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.78.1.178"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.11.1954"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.68.5.1204"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.114.002195"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1113\/JP271870"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.10.053"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.02.056"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.052808.102215"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.11.016"},{"issue":"1 suppl","key":"B14","first-page":"756.2","article-title":"Pro-arrhythmic effects of the cardiac sympathetic co-transmitter, neuropeptide-Y, during ischemia-reperfusion and ST elevation myocardial infarction","volume":"30","author":"Herring","year":"2016","journal-title":"FASEB J"},{"issue":"3","key":"B15","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1001\/jamacardio.2019.4717","article-title":"Coronary sinus neuropeptide Y levels adverse outcomes in patients with stable chronic heart failure","volume":"5","author":"Ajijola","year":"2019","journal-title":"JAMA Cardiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz115"},{"key":"B17","doi-asserted-by":"crossref","unstructured":"Kalla M, et al. The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade [published online December 13, 2019]. Eur Heart J. https:\/\/doi.org\/10.1093\/eurheartj\/ehz852","DOI":"10.1093\/eurheartj\/ehz852"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2014.080184"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2008.01436.x"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00644.2016"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.05.036"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513614"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.04.035"},{"key":"B24","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2014.00051","article-title":"\u03b21-Blockers lower norepinephrine release by inhibiting presynaptic, facilitating \u03b21-adrenoceptors in normotensive and hypertensive Rats","volume":"5","author":"Berg","year":"2014","journal-title":"Front Neurol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)60242-3"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1990.tb48930.x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(89)90193-0"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a060526"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/24.2.102"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(89)90228-3"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2012-303443"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.56.3.385"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)91325-Z"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.4.1106"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2008.043638"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007726626924"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1985.tb07671.x"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.11.001"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12407.x"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705404"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(96)00389-0"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1113\/JP271165"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2006.05.027"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.72.6.1372"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.81.1.281"},{"issue":"6","key":"B46","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.116.003264","article-title":"Which QT correction formulae to use for qt monitoring?","volume":"5","author":"Vandenberk","year":"2016","journal-title":"J Am Heart Assoc"},{"issue":"1","key":"B47","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.0954-6820.1920.tb18266.x","article-title":"Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei Herzkranken","volume":"53","author":"Fridericia","year":"1920","journal-title":"Acta Medica Scandinavica"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/135519\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:14:54Z","timestamp":1779192894000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/135519"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,4]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6,4]]},"published-print":{"date-parts":[[2020,6,4]]}},"alternative-id":["10.1172\/jci.insight.135519"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.135519","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,4]]},"article-number":"e135519"}}