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Myocardial ion channel and electrical remodeling have been described early in epilepsy development and may contribute to ventricular repolarization abnormalities and excitability. Using the pilocarpine\u2010induced acquired epilepsy model we sought to examine whether altered myocardial ion channel levels and electrophysiological changes also occur in animals with long\u2010standing epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined myocardial adrenergic receptor and ion channel protein levels of epileptic and age\u2010matched sham rats (9\u201320 months old) using western blotting. Cardiac electrical properties were examined using optical mapping ex vivo and electrophysiology in vivo. We investigated the propensity for ventricular tachycardia (<jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>) and the effects of \u03b2\u2010adrenergic blockade on ventricular electrical properties and excitability in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In animals with long\u2010standing epilepsy, we observed decreased myocardial voltage\u2010gated K<jats:sup>+<\/jats:sup>channels Kv<jats:sub>4.2<\/jats:sub>and Kv<jats:sub>4.3<\/jats:sub>, which are known to underlie early ventricular repolarization in rodents. Decreased \u03b21 and increased \u03b11<jats:sub>A<\/jats:sub>adrenergic receptor protein levels occurred in the myocardium of chronically epileptic animals consistent with elevated sympathetic tone. These animals exhibited many cardiac electrophysiological abnormalities, represented by longer<jats:styled-content style=\"fixed-case\">QRS<\/jats:styled-content>and corrected<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c) intervals in vivo, slower conduction velocity ex vivo, and stimulation\u2010induced<jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>. Administration of a \u03b2\u2010adrenergic antagonist late in epilepsy was beneficial, as the therapy shortened the<jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content>c interval and decreased stimulation\u2010induced<jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings demonstrate that myocardial ion channel remodeling and sympathetic predominance, risk factors for increased ventricular excitability and arrhythmias, persist in chronic epilepsy. The beneficial effects of \u03b2\u2010adrenergic antagonist treatment late in the course of epilepsy suggest that attenuating elevated sympathetic tone may represent a therapeutic target for ameliorating epilepsy\u2010associated cardiac morbidity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12107","type":"journal-article","created":{"date-parts":[[2018,2,16]],"date-time":"2018-02-16T15:42:44Z","timestamp":1518795764000},"page":"213-223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Myocardial remodeling and susceptibility to ventricular tachycardia in a model of chronic epilepsy"],"prefix":"10.1002","volume":"3","author":[{"given":"Yi\u2010Chen","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine Houston Texas 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