{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:48:07Z","timestamp":1740163687037,"version":"3.37.3"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC"],"award-info":[{"award-number":["ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC","ANR-10-IAHU04-LIRYC"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fondation Coeur et Recherche"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to \u03b11-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV. The \u03b11-adrenergic receptor agonist cirazoline induced a progressive loss of EFP conduction in the PV whereas it was maintained in the LA. This could be reproduced in preparations electrically paced at 5\u2009Hz in LA. During pacing at 10\u2009Hz in the PV where high firing rate ectopic foci can occur, cirazoline stopped EFP conduction from the PV to the LA, which allowed the sino-atrial node to resume its pace-making function. Loss of conduction in the PV was associated with depolarization of the diastolic membrane potential of PV cardiomyocytes. Adenosine, which reversed the cirazoline-induced depolarization of the diastolic membrane potential of PV cardiomyocytes, restored full over-shooting action potentials and EFP conduction in the PV. In conclusion, selective activation of \u03b11-adrenergic receptors results in the abolition of electrical conduction within the PV. These results highlight a potentially novel pharmacological approach to treat paroxysmal atrial fibrillation by targeting directly the PV myocardium.<\/jats:p>","DOI":"10.1038\/s41598-020-62349-5","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T11:03:32Z","timestamp":1585134212000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Selective inhibition of electrical conduction within the pulmonary veins by \u03b11-adrenergic receptors activation in the Rat"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0905-0680","authenticated-orcid":false,"given":"Pierre","family":"Bredeloux","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Findlay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00f4me","family":"Pasqualin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9l\u00e8ze","family":"Hocini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Bernus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Maupoil","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"62349_CR1","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1056\/NEJM199809033391003","volume":"339","author":"M Ha\u00efssaguerre","year":"1998","unstructured":"Ha\u00efssaguerre, M. et al. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N. Engl. J. Med. 339, 659\u2013666 (1998).","journal-title":"N. Engl. J. Med."},{"key":"62349_CR2","first-page":"1609","volume":"18","author":"P Kirchhof","year":"2016","unstructured":"Kirchhof, P. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur. Eur. Pacing Arrhythm. Card. Electrophysiol. J. Work. Groups Card. Pacing Arrhythm. Card. Cell. Electrophysiol. Eur. Soc. Cardiol. 18, 1609\u20131678 (2016).","journal-title":"Eur. Eur. Pacing Arrhythm. Card. Electrophysiol. J. Work. Groups Card. Pacing Arrhythm. Card. Cell. Electrophysiol. Eur. Soc. Cardiol."},{"key":"62349_CR3","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.12688\/f1000research.11061.1","volume":"6","author":"R Bond","year":"2017","unstructured":"Bond, R., Olshansky, B. & Kirchhof, P. Recent advances in rhythm control for atrial fibrillation. F1000Research 6, 1796 (2017).","journal-title":"F1000Research"},{"key":"62349_CR4","doi-asserted-by":"publisher","first-page":"2368","DOI":"10.1161\/CIRCULATIONAHA.110.946806","volume":"122","author":"F Ouyang","year":"2010","unstructured":"Ouyang, F. et al. Long-term results of catheter ablation in paroxysmal atrial fibrillation: lessons from a 5-year follow-up. Circulation 122, 2368\u20132377 (2010).","journal-title":"Circulation"},{"key":"62349_CR5","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2174\/157340312803760802","volume":"8","author":"L Roten","year":"2012","unstructured":"Roten, L. et al. Current hot potatoes in atrial fibrillation ablation. Curr. Cardiol. Rev. 8, 327\u2013346 (2012).","journal-title":"Curr. Cardiol. Rev."},{"key":"62349_CR6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.2174\/187152509787047621","volume":"7","author":"D Li","year":"2009","unstructured":"Li, D., Sun, H. & Levesque, P. Antiarrhythmic drug therapy for atrial fibrillation: focus on atrial selectivity and safety. Cardiovasc. Hematol. Agents Med. Chem. 7, 64\u201375 (2009).","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"62349_CR7","first-page":"340","volume":"18","author":"SJ Podd","year":"2016","unstructured":"Podd, S. J., Freemantle, N., Furniss, S. S. & Sulke, N. First clinical trial of specific IKACh blocker shows no reduction in atrial fibrillation burden in patients with paroxysmal atrial fibrillation: pacemaker assessment of BMS 914392 in patients with paroxysmal atrial fibrillation. Eur. Eur. Pacing Arrhythm. Card. Electrophysiol. J. Work. Groups Card. Pacing Arrhythm. Card. Cell. Electrophysiol. Eur. Soc. Cardiol. 18, 340\u2013346 (2016).","journal-title":"Eur. Eur. Pacing Arrhythm. Card. Electrophysiol. J. Work. Groups Card. Pacing Arrhythm. Card. Cell. Electrophysiol. Eur. Soc. Cardiol."},{"key":"62349_CR8","doi-asserted-by":"publisher","first-page":"H102","DOI":"10.1152\/ajpheart.00256.2009","volume":"297","author":"N Doisne","year":"2009","unstructured":"Doisne, N., Maupoil, V., Cosnay, P. & Findlay, I. Catecholaminergic automatic activity in the rat pulmonary vein: electrophysiological differences between cardiac muscle in the left atrium and pulmonary vein. Am. J. Physiol. Heart Circ. Physiol. 297, H102\u2013108 (2009).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"62349_CR9","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/sj.bjp.0707177","volume":"150","author":"V Maupoil","year":"2007","unstructured":"Maupoil, V., Bronquard, C., Freslon, J.-L., Cosnay, P. & Findlay, I. Ectopic activity in the rat pulmonary vein can arise from simultaneous activation of alpha1- and beta1-adrenoceptors. Br. J. Pharmacol. 150, 899\u2013905 (2007).","journal-title":"Br. J. Pharmacol."},{"key":"62349_CR10","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1124\/pr.112.007203","volume":"66","author":"TD O\u2019Connell","year":"2014","unstructured":"O\u2019Connell, T. D., Jensen, B. C., Baker, A. J. & Simpson, P. C. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol. Rev. 66, 308\u2013333 (2014).","journal-title":"Pharmacol. Rev."},{"key":"62349_CR11","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jacbts.2016.03.005","volume":"1","author":"RC Thomas","year":"2016","unstructured":"Thomas, R. C. et al. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart. JACC Basic Transl. Sci. 1, 155\u2013167 (2016).","journal-title":"JACC Basic Transl. Sci."},{"key":"62349_CR12","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1016\/j.jacc.2014.05.077","volume":"64","author":"Y-K Iwasaki","year":"2014","unstructured":"Iwasaki, Y.-K. et al. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model. J. Am. Coll. Cardiol. 64, 2013\u20132023 (2014).","journal-title":"J. Am. Coll. Cardiol."},{"key":"62349_CR13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1161\/CIRCRESAHA.113.301646","volume":"113","author":"A Parikh","year":"2013","unstructured":"Parikh, A. et al. Relaxin suppresses atrial fibrillation by reversing fibrosis and myocyte hypertrophy and increasing conduction velocity and sodium current in spontaneously hypertensive rat hearts. Circ. Res. 113, 313\u2013321 (2013).","journal-title":"Circ. Res."},{"key":"62349_CR14","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1111\/jce.12738","volume":"26","author":"YV Egorov","year":"2015","unstructured":"Egorov, Y. V., Kuz\u2019min, V. S., Glukhov, A. V. & Rosenshtraukh, L. V. Electrophysiological Characteristics, Rhythm, Disturbances and Conduction Discontinuities Under Autonomic Stimulation in the Rat Pulmonary Vein Myocardium. J. Cardiovasc. Electrophysiol. 26, 1130\u20131139 (2015).","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"62349_CR15","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.cardiores.2004.08.014","volume":"65","author":"P Melnyk","year":"2005","unstructured":"Melnyk, P. et al. Comparison of ion channel distribution and expression in cardiomyocytes of canine pulmonary veins versus left atrium. Cardiovasc. Res. 65, 104\u2013116 (2005).","journal-title":"Cardiovasc. Res."},{"key":"62349_CR16","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1161\/01.RES.68.4.1035","volume":"68","author":"E Ragazzi","year":"1991","unstructured":"Ragazzi, E., Wu, S. N., Shryock, J. & Belardinelli, L. Electrophysiological and receptor binding studies to assess activation of the cardiac adenosine receptor by adenine nucleotides. Circ. Res. 68, 1035\u20131044 (1991).","journal-title":"Circ. Res."},{"key":"62349_CR17","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1097\/FJC.0b013e3182965221","volume":"62","author":"X Wang","year":"2013","unstructured":"Wang, X. et al. GIRK channel activation via adenosine or muscarinic receptors has similar effects on rat atrial electrophysiology. J. Cardiovasc. Pharmacol. 62, 192\u2013198 (2013).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"62349_CR18","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1161\/CIRCULATIONAHA.109.893107","volume":"121","author":"T Datino","year":"2010","unstructured":"Datino, T. et al. Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins. Circulation 121, 963\u2013972 (2010).","journal-title":"Circulation"},{"key":"62349_CR19","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/BF00370253","volume":"421","author":"AP Braun","year":"1992","unstructured":"Braun, A. P., Fedida, D. & Giles, W. R. Activation of alpha 1-adrenoceptors modulates the inwardly rectifying potassium currents of mammalian atrial myocytes. Pflugers Arch. 421, 431\u2013439 (1992).","journal-title":"Pflugers Arch."},{"key":"62349_CR20","doi-asserted-by":"publisher","first-page":"4643","DOI":"10.1073\/pnas.0408844102","volume":"102","author":"H Cho","year":"2005","unstructured":"Cho, H., Lee, D., Lee, S. H. & Ho, W.-K. Receptor-induced depletion of phosphatidylinositol 4,5-bisphosphate inhibits inwardly rectifying K+ channels in a receptor-specific manner. Proc. Natl. Acad. Sci. USA 102, 4643\u20134648 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"62349_CR21","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1113\/jphysiol.2003.046417","volume":"551","author":"JR Ehrlich","year":"2003","unstructured":"Ehrlich, J. R. et al. Cellular electrophysiology of canine pulmonary vein cardiomyocytes: action potential and ionic current properties. J. Physiol. 551, 801\u2013813 (2003).","journal-title":"J. Physiol."},{"key":"62349_CR22","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1248\/bpb.b212020","volume":"36","author":"I Namekata","year":"2013","unstructured":"Namekata, I., Tsuneoka, Y. & Tanaka, H. Electrophysiological and pharmacological properties of the pulmonary vein myocardium. Biol. Pharm. Bull. 36, 2\u20137 (2013).","journal-title":"Biol. Pharm. Bull."},{"key":"62349_CR23","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/jce.12572","volume":"26","author":"CO Mal\u00e9cot","year":"2015","unstructured":"Mal\u00e9cot, C. O., Bredeloux, P., Findlay, I. & Maupoil, V. A TTX-sensitive resting Na+ permeability contributes to the catecholaminergic automatic activity in rat pulmonary vein. J. Cardiovasc. Electrophysiol. 26, 311\u2013319 (2015).","journal-title":"J. Cardiovasc. Electrophysiol."},{"key":"62349_CR24","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.yjmcc.2012.01.007","volume":"52","author":"Y Okamoto","year":"2012","unstructured":"Okamoto, Y., Takano, M., Ohba, T. & Ono, K. Arrhythmogenic coupling between the Na+ -Ca2+ exchanger and inositol 1,4,5-triphosphate receptor in rat pulmonary vein cardiomyocytes. J. Mol. Cell. Cardiol. 52, 988\u2013997 (2012).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"62349_CR25","doi-asserted-by":"publisher","first-page":"e012748","DOI":"10.1161\/JAHA.119.012748","volume":"8","author":"YV Egorov","year":"2019","unstructured":"Egorov, Y. V. et al. Caveolae-Mediated Activation of Mechanosensitive Chloride Channels in Pulmonary Veins Triggers Atrial Arrhythmogenesis. J. Am. Heart Assoc. 8, e012748 (2019).","journal-title":"J. Am. Heart Assoc."},{"key":"62349_CR26","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.yjmcc.2013.11.002","volume":"66","author":"Y Okamoto","year":"2014","unstructured":"Okamoto, Y., Kawamura, K., Nakamura, Y. & Ono, K. Pathological impact of hyperpolarization-activated chloride current peculiar to rat pulmonary vein cardiomyocytes. J. Mol. Cell. Cardiol. 66, 53\u201362 (2014).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"62349_CR27","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1161\/CIRCULATIONAHA.108.825380","volume":"119","author":"EJ Benjamin","year":"2009","unstructured":"Benjamin, E. J. et al. Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop. Circulation. 119, 606\u201318 (2009).","journal-title":"Circulation."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62349-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62349-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62349-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T08:54:02Z","timestamp":1670316842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-62349-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["62349"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-62349-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2020,3,25]]},"assertion":[{"value":"30 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5390"}}