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Chronic obstructive pulmonary disease (COPD) and right ventricular outflow tract (RVOT) constitute the primary risk factor and origin of VT, respectively. To investigate the arrhythmogenesis of nicotine in COPD, we employed tachypacing with or without H89, KN93 and KB\u2010R7943 treatment, along with patch clamp experiments and Masson's trichrome staining in control rabbits and rabbits with human leukocyte elastase (0.3 unit\/kg)\u2010induced COPD. Following 20\u2010Hz tachypacing and isoproterenol treatment, COPD RVOTs had a higher VT incidence than control RVOTs. Nicotine\u2010treated COPD RVOTs had higher ventricular arrhythmogenesis than non\u2010treated COPD RVOTs. VTs induced in COPD and nicotine\u2010treated COPD RVOTs were suppressed by H89, KN93, or KB\u2010R7943. COPD RVOT myocytes exhibited shorter action potentials than control RVOT myocytes; nicotine\u2010treated COPD RVOT myocytes exhibited longer action potentials than COPD RVOT myocytes. Both COPD and nicotine\u2010treated COPD myocytes had smaller L\u2010type Ca<jats:sup>2+<\/jats:sup> currents and larger NCX currents than control RVOT myocytes. Nicotine\u2010treated COPD RVOT myocytes had larger late Na<jats:sup>+<\/jats:sup> currents than control and COPD RVOT myocytes. COPD and nicotine\u2010treated COPD RVOTs exhibited more fibrosis. Nicotine\u2010treated COPD RVOTs had the highest level of fibrosis. COPD intensifies RVOT VT through electrical and structural remodelling and Ca<jats:sup>2+<\/jats:sup> dysregulation through the activation of PKA, CaMKII and NCX signalling pathways. Nicotine further exacerbates VTs in the rabbit RVOT triggered by COPD.<\/jats:p>","DOI":"10.1111\/jcmm.70664","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T08:08:52Z","timestamp":1751011732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nicotine Exacerbates Arrhythmogenesis in Rabbit Right Ventricular Outflow Tract Triggered by Chronic Obstructive Pulmonary Disease"],"prefix":"10.1111","volume":"29","author":[{"given":"Chao\u2010Shun","family":"Chan","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine Taipei Medical University  Taipei Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine Taipei Medical University Hospital, Taipei Medical University  Taipei 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