{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T03:49:34Z","timestamp":1770608974225,"version":"3.49.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,9,18]]},"abstract":"\n Background<\/jats:title>\n \n SERCA<\/jats:styled-content>\n 2a gene transfer (\n GT<\/jats:styled-content>\n ) improves mechano\u2010electrical function in animal models of nonischemic heart failure Whether\n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n reverses pre\u2010established remodeling at an advanced stage of ischemic heart failure is unclear. We sought to uncover the electrophysiological effects of adeno\u2010associated virus serotype 1.\n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n following myocardial infarction (\n MI<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Pigs developed mechanical dysfunction 1 month after anterior\n MI<\/jats:styled-content>\n , at which point they received intracoronary adeno\u2010associated virus serotype 1.\n SERCA<\/jats:styled-content>\n 2a (\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a) or saline (\n MI<\/jats:styled-content>\n ) and were maintained for 2 months. Age\u2010matched naive pigs served as controls (Control). In vivo\n ECG<\/jats:styled-content>\n \u2010and\u2010hemodynamic properties were assessed before and after dobutamine stress. The electrophysiological substrate was measured using optical action potential (\n AP<\/jats:styled-content>\n ) mapping in controls,\n MI<\/jats:styled-content>\n , and\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a preparations. In vivo\n ECG<\/jats:styled-content>\n measurements revealed comparable\n QT<\/jats:styled-content>\n durations between groups. In contrast, prolonged\n QRS<\/jats:styled-content>\n duration and increased frequency of R\u2032 waves were present in\n MI<\/jats:styled-content>\n but not\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a pigs relative to controls.\n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n reduced in in\u00a0vivo arrhythmias in response to dobutamine. Ex vivo preparations from\n MI<\/jats:styled-content>\n but not\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a or control pigs were prone to pacing\u2010induced ventricular tachycardia and fibrillation. Underlying these arrhythmias was pronounced conduction velocity slowing in\n MI<\/jats:styled-content>\n versus\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a at elevated rates leading to ventricular tachycardia and fibrillation. Reduced susceptibility to ventricular tachycardia and fibrillation in\n MI<\/jats:styled-content>\n +\n SERCA<\/jats:styled-content>\n 2a pigs was not related to hemodynamic function, contractile reserve, fibrosis, or the expression of Cx43 and Nav1.5. Rather,\n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n decreased phosphoactive\n CAMKII<\/jats:styled-content>\n \u2010delta levels by >50%, leading to improved excitability at fast rates.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n increases conduction velocity reserve, likely by preventing\n CAMKII<\/jats:styled-content>\n overactivation. Our findings suggest a primary effect of\n SERCA<\/jats:styled-content>\n 2a\n GT<\/jats:styled-content>\n on myocardial excitability, independent of altered mechanical function.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.118.009598","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T01:26:33Z","timestamp":1537147593000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction"],"prefix":"10.1161","volume":"7","author":[{"given":"Lukas J.","family":"Motloch","sequence":"first","affiliation":[{"name":"Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NY"},{"name":"Department of Internal Medicine II Paracelsus Medical University Salzburg 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NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaume","family":"Aguero","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth M.","family":"Fish","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger J.","family":"Hajjar","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York NY"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fadi G.","family":"Akar","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center Icahn School of Medicine at Mount Sinai New York 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