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This study examined whether the activation\u2013repolarization coupling plays a role in coordinating repolarization times between the right ventricular (<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>) and left ventricular (<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>) chambers, and if impaired coordination contributes to electrical instability produced by hypokalaemia or dofetilide, a blocker of the delayed rectifier<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content><jats:sup>+<\/jats:sup>current.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In Langendorff\u2010perfused, isolated guinea pig hearts, six monophasic action potential recording electrodes were attached to<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>epicardium. Local activation time and action potential duration (<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>) were determined during spontaneous beating, regular pacing and extrasystolic excitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In regularly beating hearts, the<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>epicardial sites had longer<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>, but exhibited earlier activation times, as compared to<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>sites, which minimized the interventricular difference in repolarization time. Upon extrasystolic stimulation, the<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>was reduced to a greater extent in<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>compared with<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>, which translated to a reversed slope of<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>\u2010to\u2010activation time relationship, and increased spatial repolarization gradients. Hypokalaemia and dofetilide prolonged<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>, with the effect being greater in<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>compared with<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>. In hypokalaemic hearts,<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>activation was delayed. These changes contributed to increased asynchrony in repolarization times in the<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>in both regular and extrasystolic beats, and enhanced susceptibility to tachyarrhythmia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Impaired<jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\u2010to\u2010<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>activation\u2013repolarization coupling is an important determinant of electrical instability in the setting of non\u2010uniformly prolonged epicardial<jats:styled-content style=\"fixed-case\">APD<\/jats:styled-content><jats:sub>90<\/jats:sub>or slowed interventricular conduction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12259","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T18:45:28Z","timestamp":1392662728000},"page":"48-60","source":"Crossref","is-referenced-by-count":12,"title":["Impaired epicardial activation\u2013repolarization coupling contributes to the proarrhythmic effects of hypokalaemia and dofetilide in guinea pig ventricles"],"prefix":"10.1111","volume":"211","author":[{"given":"O. 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