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Because sympathetic remodelling is challenging to control experimentally, we created and validated a novel ionic model incorporating the macroscopic effects of BARS on intracellular Ca\n 2+<\/jats:sup>\n dynamics and handling for tissue\u2010scale simulations. Using our model we created ventricular sheets with varying spatial densities and gradients to study VT behaviour, represented as a rotor. We demonstrated that our BARS model reduces action potential durations (APDs) by 16% due to drastic changes in K\n +<\/jats:sup>\n and Ca\n 2+<\/jats:sup>\n regulation, consistent with experimental data from animal and human studies. We also demonstrated that the ventricular substrate with spatial BARS density for \u00b5M (ISO) could host faster (4.5 Hz\n vs<\/jats:italic>\n . 3.7 Hz) and more stable (5.6\u00a0mm\n 2<\/jats:sup>\n vs<\/jats:italic>\n . 14\u00a0mm\n 2<\/jats:sup>\n ) VTs than non\u2010BARS substrates. We also showed that VTs hosted in substrates with spatial BARS gradients ( could splinter into multiple slow and disorganized wavelets, indicative of fibrillation. Our model and simulation findings may help predict and enhance the effectiveness of neuromodulatory interventions for sympathetically modulated VTs.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n A novel human ventricular model is used for tissue\u2010scale simulation of sympathetic activity<\/jats:p>\n <\/jats:list-item>\n \n Sympathetically remodelled substrates may have fast and stable rotors<\/jats:p>\n <\/jats:list-item>\n \n Spatial gradients of sympathetic stimulation could break rotors into wavelets<\/jats:p>\n <\/jats:list-item>\n \n Simulations may help inform interventions for sympathetically modulated arrhythmias<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289340","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T13:25:07Z","timestamp":1769865907000},"page":"1897-1914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A model of \u03b2\u2010adrenergic stimulation in human ventricular cells for tissue\u2010scale simulations of sympathetically modulated tachycardias"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-4569","authenticated-orcid":false,"given":"Kelly","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5846-5327","authenticated-orcid":false,"given":"Karl","family":"Magtibay","sequence":"additional","affiliation":[{"name":"Institut de Math\u00e9matiques de Bordeaux Universit\u00e9 de Bordeaux Talence Gironde France"},{"name":"IHU L'institut des maladies du rythme cardiaque (Liryc) H\u00f4pital Xavier Arnozan Pessac Gironde France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-063X","authenticated-orcid":false,"given":"Natalia","family":"Trayanova","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1388-3589","authenticated-orcid":false,"given":"Edward","family":"Vigmond","sequence":"additional","affiliation":[{"name":"Institut de Math\u00e9matiques de Bordeaux Universit\u00e9 de Bordeaux Talence Gironde France"},{"name":"IHU L'institut des maladies du rythme cardiaque (Liryc) H\u00f4pital Xavier Arnozan Pessac Gironde France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.124222"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.06.021"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.88.6.2501"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.09.030"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2010.05.008"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP281118"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000258172.74570.e6"},{"issue":"22","key":"e_1_2_5_9_1","article-title":"Heterogeneous cardiac sympathetic innervation gradients promote arrhythmogenesis in Murine dilated cardiomyopathy","volume":"8","author":"Dajani A.l\u2010H. 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