{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:16:31Z","timestamp":1784891791876,"version":"3.55.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T00:00:00Z","timestamp":1600041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ventricular arrhythmias are a major source of early mortality in acute myocardial infarction (MI) and remain a major therapeutic challenge. Thus we investigated effects of ivabradine, a presumably specific bradycardic agent versus metoprolol, a \u03b2-blocker, at doses offering the same heart rate (HR) reduction, on ventricular arrhythmias in the acute non-reperfused MI in the rat. Immediately after MI induction a single dose of ivabradine\/ metoprolol was given. ECG was continuously recorded and ventricular arrhythmias were analyzed. After 6\u00a0h epicardial monophasic action potentials (MAPs) were recorded and cardiomyocyte Ca<jats:sup>2+<\/jats:sup> handling was assessed. Both ivabradine and metoprolol reduced HR by 17% and arrhythmic mortality (14% and 19%, respectively, versus 33% in MI, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and ventricular arrhythmias in post-MI rats. Both drugs reduced QTc prolongation and decreased sensitivity of ryanodine receptors in isolated cardiomyocytes, but otherwise had no effect on Ca<jats:sup>2+<\/jats:sup> handling, velocity of conduction or repolarization. We did not find any effects of potential <jats:italic>I<\/jats:italic><jats:sub>Kr<\/jats:sub> inhibition by ivabradine in this setting. Thus Ivabradine is an equally effective antiarrhythmic agent as metoprolol in early MI in the rat. It could be potentially tested as an alternative antiarrhythmic agent in acute MI when \u03b2-blockers are contraindicated.<\/jats:p>","DOI":"10.1038\/s41598-020-71706-3","type":"journal-article","created":{"date-parts":[[2020,9,14]],"date-time":"2020-09-14T10:03:01Z","timestamp":1600077781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ivabradine is as effective as metoprolol in the prevention of ventricular arrhythmias in acute non-reperfused myocardial infarction in the rat"],"prefix":"10.1038","volume":"10","author":[{"given":"Mariusz","family":"Marciszek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Paterek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Okni\u0144ska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Mackiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-4141","authenticated-orcid":false,"given":"Micha\u0142","family":"M\u0105czewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,14]]},"reference":[{"key":"71706_CR1","doi-asserted-by":"publisher","first-page":"2074","DOI":"10.1161\/CIRCULATIONAHA.116.022954","volume":"134","author":"N Karam","year":"2016","unstructured":"Karam, N. et al. Identifying patients at risk for prehospital sudden cardiac arrest at the early phase of myocardial infarction. Circulation 134, 2074\u20132083. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.116.022954 (2016).","journal-title":"Circulation"},{"key":"71706_CR2","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1056\/nejm198303173081102","volume":"308","author":"L Ryd\u00e9n","year":"1983","unstructured":"Ryd\u00e9n, L. et al. A double-blind trial of metoprolol in acute myocardial infarction. N. Engl. J. Med. 308, 614\u2013618. https:\/\/doi.org\/10.1056\/nejm198303173081102 (1983).","journal-title":"N. Engl. J. Med."},{"key":"71706_CR3","doi-asserted-by":"publisher","first-page":"43F","DOI":"10.1016\/0002-9149(86)90888-X","volume":"57","author":"JK Kjekshus","year":"1986","unstructured":"Kjekshus, J. K. Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. Am. J. Cardiol. 57, 43F-49F (1986).","journal-title":"Am. J. Cardiol."},{"key":"71706_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.2165\/00003495-200767002-00003","volume":"67","author":"D DiFrancesco","year":"2007","unstructured":"DiFrancesco, D. & Borer, J. S. The funny current. Drugs 67, 15\u201324. https:\/\/doi.org\/10.2165\/00003495-200767002-00003 (2007).","journal-title":"Drugs"},{"key":"71706_CR5","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1002\/jcp.24507","volume":"229","author":"U Mackiewicz","year":"2014","unstructured":"Mackiewicz, U. et al. Ivabradine protects against ventricular arrhythmias in acute myocardial infarction in the rat. J. Cell. Physiol. 229, 813\u2013823. https:\/\/doi.org\/10.1002\/jcp.24507 (2014).","journal-title":"J. Cell. Physiol."},{"key":"71706_CR6","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/sj.bjp.0706231","volume":"145","author":"H Clements-Jewery","year":"2005","unstructured":"Clements-Jewery, H., Hearse, D. J. & Curtis, M. J. Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation. Br. J. Pharmacol. 145, 551\u2013564. https:\/\/doi.org\/10.1038\/sj.bjp.0706231 (2005).","journal-title":"Br. J. Pharmacol."},{"key":"71706_CR7","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1476-5381.1985.tb09453.x","volume":"86","author":"I Lepr\u00e1n","year":"1985","unstructured":"Lepr\u00e1n, I., Parratt, J. R., Szekeres, L. & Wainwright, C. L. The effects of metoprolol and dazmegrel, alone and in combination, on arrhythmias induced by coronary artery occlusion in conscious rats. Br. J. Pharmacol. 86, 229\u2013234. https:\/\/doi.org\/10.1111\/j.1476-5381.1985.tb09453.x (1985).","journal-title":"Br. J. Pharmacol."},{"key":"71706_CR8","doi-asserted-by":"publisher","first-page":"e001813","DOI":"10.1161\/JAHA.115.001813","volume":"4","author":"D Melgari","year":"2015","unstructured":"Melgari, D. et al. hERG potassium channel blockade by the HCN channel inhibitor bradycardic agent ivabradine. J. Am. Heart Assoc. 4, e001813. https:\/\/doi.org\/10.1161\/JAHA.115.001813 (2015).","journal-title":"J. Am. Heart Assoc."},{"key":"71706_CR9","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/nature04710","volume":"440","author":"MC Sanguinetti","year":"2006","unstructured":"Sanguinetti, M. C. & Tristani-Firouzi, M. hERG potassium channels and cardiac arrhythmia. Nature 440, 463\u2013469. https:\/\/doi.org\/10.1038\/nature04710 (2006).","journal-title":"Nature"},{"key":"71706_CR10","doi-asserted-by":"publisher","first-page":"5068","DOI":"10.1096\/fj.201700255R","volume":"31","author":"SM Lamothe","year":"2017","unstructured":"Lamothe, S. M. et al. Hypoxia reduces mature hERG channels through calpain up-regulation. FASEB J. 31, 5068\u20135077. https:\/\/doi.org\/10.1096\/fj.201700255R (2017).","journal-title":"FASEB J."},{"key":"71706_CR11","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s12012-018-9482-y","volume":"19","author":"G Frommeyer","year":"2019","unstructured":"Frommeyer, G. et al. Ivabradine aggravates the proarrhythmic risk in experimental models of long QT syndrome. Cardiovasc. Toxicol. 19, 129\u2013135. https:\/\/doi.org\/10.1007\/s12012-018-9482-y (2019).","journal-title":"Cardiovasc. Toxicol."},{"key":"71706_CR12","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s12012-014-9274-y","volume":"15","author":"G Cocco","year":"2015","unstructured":"Cocco, G. & Jerie, P. Torsades de pointes induced by the concomitant use of ivabradine and azithromycin: an unexpected dangerous interaction. Cardiovasc. Toxicol. 15, 104\u2013106. https:\/\/doi.org\/10.1007\/s12012-014-9274-y (2015).","journal-title":"Cardiovasc. Toxicol."},{"key":"71706_CR13","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1136\/heartjnl-2014-305482","volume":"100","author":"RIR Martin","year":"2014","unstructured":"Martin, R. I. R. et al. Atrial fibrillation associated with ivabradine treatment: meta-analysis of randomised controlled trials. Heart 100, 1506\u20131510. https:\/\/doi.org\/10.1136\/heartjnl-2014-305482 (2014).","journal-title":"Heart"},{"key":"71706_CR14","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.12659\/MSM.894320","volume":"21","author":"YD Li","year":"2015","unstructured":"Li, Y. D. et al. Effects of ivabradine on cardiac electrophysiology in dogs with age-related atrial fibrillation. Med. Sci. Monit. 21, 1414\u20131420. https:\/\/doi.org\/10.12659\/MSM.894320 (2015).","journal-title":"Med. Sci. Monit."},{"key":"71706_CR15","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1152\/physrev.1989.69.4.1049","volume":"69","author":"MJ Janse","year":"1989","unstructured":"Janse, M. J. & Wit, A. L. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol. Rev. 69, 1049\u20131169. https:\/\/doi.org\/10.1152\/physrev.1989.69.4.1049 (1989).","journal-title":"Physiol. Rev."},{"key":"71706_CR16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1146\/annurev-physiol-021014-071622","volume":"77","author":"Z Qu","year":"2015","unstructured":"Qu, Z. & Weiss, J. N. Mechanisms of ventricular arrhythmias: from molecular fluctuations to electrical turbulence. Annu. Rev. Physiol. 77, 29\u201355. https:\/\/doi.org\/10.1146\/annurev-physiol-021014-071622 (2015).","journal-title":"Annu. Rev. Physiol."},{"key":"71706_CR17","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41569-019-0179-0","volume":"16","author":"S Clauss","year":"2019","unstructured":"Clauss, S. et al. Animal models of arrhythmia: classic electrophysiology to genetically modified large animals. Nat. Rev. Cardiol. 16, 457\u2013475. https:\/\/doi.org\/10.1038\/s41569-019-0179-0 (2019).","journal-title":"Nat. Rev. Cardiol."},{"key":"71706_CR18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1161\/01.RES.85.1.38","volume":"85","author":"B Pieske","year":"1999","unstructured":"Pieske, B., Maier Lars, S., Bers Donald, M. & Hasenfuss, G. Ca2+ handling and sarcoplasmic reticulum Ca2+ content in isolated failing and nonfailing human myocardium. Circul. Res. 85, 38\u201346. https:\/\/doi.org\/10.1161\/01.RES.85.1.38 (1999).","journal-title":"Circul. Res."},{"key":"71706_CR19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.ejphar.2010.05.038","volume":"641","author":"J Kmecova","year":"2010","unstructured":"Kmecova, J. & Klimas, J. Heart rate correction of the QT duration in rats. Eur. J. Pharmacol. 641, 187\u2013192. https:\/\/doi.org\/10.1016\/j.ejphar.2010.05.038 (2010).","journal-title":"Eur. J. Pharmacol."},{"key":"71706_CR20","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cardiores.2005.01.014","volume":"66","author":"N Zeevi-Levin","year":"2005","unstructured":"Zeevi-Levin, N. et al. Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes. Cardiovasc. Res. 66, 64\u201373. https:\/\/doi.org\/10.1016\/j.cardiores.2005.01.014 (2005).","journal-title":"Cardiovasc. Res."},{"key":"71706_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0008-6363(98)00268-5","volume":"41","author":"MR Franz","year":"1999","unstructured":"Franz, M. R. Current status of monophasic action potential recording: theories, measurements and interpretations. Cardiovasc. Res. 41, 25\u201340. https:\/\/doi.org\/10.1016\/s0008-6363(98)00268-5 (1999).","journal-title":"Cardiovasc. Res."},{"key":"71706_CR22","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1016\/j.yjmcc.2009.12.016","volume":"48","author":"U Mackiewicz","year":"2009","unstructured":"Mackiewicz, U. et al. Brief postinfarction calcineurin blockade affects left ventricular remodeling and Ca2+ handling in the rat. J. Mol. Cell. Cardiol. 48, 1307\u20131315. https:\/\/doi.org\/10.1016\/j.yjmcc.2009.12.016 (2009).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"71706_CR23","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/cvr\/cvw111","volume":"112","author":"M Frisk","year":"2016","unstructured":"Frisk, M. et al. Elevated ventricular wall stress disrupts cardiomyocyte t-tubule structure and calcium homeostasis. Cardiovasc. Res. 112, 443\u2013451. https:\/\/doi.org\/10.1093\/cvr\/cvw111 (2016).","journal-title":"Cardiovasc. Res."},{"key":"71706_CR24","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1152\/ajpheart.00423.2005","volume":"289","author":"H Ashikaga","year":"2005","unstructured":"Ashikaga, H. et al. Electromechanical analysis of infarct border zone in chronic myocardial infarction. Am. J. Physiol. Heart Circul. Physiol. 289, 1099\u20131105. https:\/\/doi.org\/10.1152\/ajpheart.00423.2005 (2005).","journal-title":"Am. J. Physiol. Heart Circul. Physiol."},{"key":"71706_CR25","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.pbiomolbio.2008.02.023","volume":"97","author":"TG McNary","year":"2008","unstructured":"McNary, T. G., Sohn, K., Taccardi, B. & Sachse, F. B. Experimental and computational studies of strain\u2013conduction velocity relationships in cardiac tissue. Prog. Biophys. Mol. Biol. 97, 383\u2013400. https:\/\/doi.org\/10.1016\/j.pbiomolbio.2008.02.023 (2008).","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"71706_CR26","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/S0735-1097(02)02864-4","volume":"41","author":"V Probst","year":"2003","unstructured":"Probst, V. et al. Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Len\u00e8gre disease. J. Am. Coll. Cardiol. 41, 643\u2013652. https:\/\/doi.org\/10.1016\/S0735-1097(02)02864-4 (2003).","journal-title":"J. Am. Coll. Cardiol."},{"key":"71706_CR27","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.hrthm.2014.11.034","volume":"12","author":"J Shenthar","year":"2015","unstructured":"Shenthar, J., Deora, S., Rai, M. & Nanjappa Manjunath, C. Prolonged Tpeak-end and Tpeak-end\/QT ratio as predictors of malignant ventricular arrhythmias in the acute phase of ST-segment elevation myocardial infarction: A prospective case-control study. Heart Rhythm 12, 484\u2013489. https:\/\/doi.org\/10.1016\/j.hrthm.2014.11.034 (2015).","journal-title":"Heart Rhythm"},{"key":"71706_CR28","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.vascn.2013.01.003","volume":"68","author":"HR Lu","year":"2013","unstructured":"Lu, H. R., Yan, G.-X. & Gallacher, D. J. A new biomarker\u2014index of cardiac electrophysiological balance (iCEB)\u2014plays an important role in drug-induced cardiac arrhythmias: beyond QT-prolongation and Torsades de Pointes (TdPs). J. Pharmacol. Toxicol. Methods 68, 250\u2013259. https:\/\/doi.org\/10.1016\/j.vascn.2013.01.003 (2013).","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"71706_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.yjmcc.2010.07.012","volume":"49","author":"AAM Wilde","year":"2010","unstructured":"Wilde, A. A. M. et al. The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization. J. Mol. Cell. Cardiol. 49, 543\u2013553. https:\/\/doi.org\/10.1016\/j.yjmcc.2010.07.012 (2010).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"71706_CR30","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.yjmcc.2013.02.001","volume":"59","author":"FS Ng","year":"2013","unstructured":"Ng, F. S., Shadi, I. T., Peters, N. S. & Lyon, A. R. Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia-reperfusion-induced ventricular arrhythmias. J. Mol. Cell. Cardiol. 59, 67\u201375. https:\/\/doi.org\/10.1016\/j.yjmcc.2013.02.001 (2013).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"71706_CR31","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1097\/FJC.0b013e3181913df4","volume":"52","author":"F Vaillant","year":"2008","unstructured":"Vaillant, F. et al. Ivabradine induces an increase in ventricular fibrillation threshold during acute myocardial ischemia: an experimental study. J. Cardiovasc. Pharmacol. 52, 548\u2013554. https:\/\/doi.org\/10.1097\/FJC.0b013e3181913df4 (2008).","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"71706_CR32","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.yjmcc.2015.06.008","volume":"96","author":"KM Holzem","year":"2016","unstructured":"Holzem, K. M. et al. Reduced response to IKr blockade and altered hERG1a\/1b stoichiometry in human heart failure. J. Mol. Cell. Cardiol. 96, 82\u201392. https:\/\/doi.org\/10.1016\/j.yjmcc.2015.06.008 (2016).","journal-title":"J. Mol. Cell. Cardiol."},{"key":"71706_CR33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/cvr\/cvn057","volume":"79","author":"M M\u0105czewski","year":"2008","unstructured":"M\u0105czewski, M. & Mackiewicz, U. Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart. Cardiovasc. Res. 79, 42\u201351. https:\/\/doi.org\/10.1093\/cvr\/cvn057 (2008).","journal-title":"Cardiovasc. Res."},{"key":"71706_CR34","doi-asserted-by":"publisher","first-page":"15758","DOI":"10.1038\/s41598-018-33277-2","volume":"8","author":"A Paterek","year":"2018","unstructured":"Paterek, A. et al. Beneficial effects of intravenous iron therapy in a rat model of heart failure with preserved systemic iron status but depleted intracellular cardiac stores. Sci. Rep. 8, 15758. https:\/\/doi.org\/10.1038\/s41598-018-33277-2 (2018).","journal-title":"Sci. Rep."},{"key":"71706_CR35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1161\/01.CIR.92.2.253","volume":"92","author":"CF Opitz","year":"1995","unstructured":"Opitz, C. F., Mitchell, G. F., Pfeffer, M. A. & Pfeffer, J. M. Arrhythmias and death after coronary artery occlusion in the rat. Circulation 92, 253\u2013261. https:\/\/doi.org\/10.1161\/01.CIR.92.2.253 (1995).","journal-title":"Circulation"},{"key":"71706_CR36","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.pharmthera.2013.04.008","volume":"139","author":"MJ Curtis","year":"2013","unstructured":"Curtis, M. J. et al. The Lambeth Conventions (II): Guidelines for the study of animal and human ventricular and supraventricular arrhythmias. Pharmacol. Ther. 139, 213\u2013248. https:\/\/doi.org\/10.1016\/j.pharmthera.2013.04.008 (2013).","journal-title":"Pharmacol. Ther."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71706-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71706-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71706-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T18:36:34Z","timestamp":1670351794000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71706-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,14]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["71706"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-71706-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,14]]},"assertion":[{"value":"3 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 September 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":"15027"}}