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We investigated omecamtiv mecarbil in a Langendorff-perfused rabbit heart model. Forty-eight rabbit hearts were retrogradely perfused; twenty-four in a ventricular and twenty-four in an atrial setup. In the ventricular setup, action potential duration at 90% repolarization (APD\n                    <jats:sub>90<\/jats:sub>\n                    ), QT interval, and dispersion of repolarization were assessed during pacing at seven cycle lengths. After baseline recordings, Group 1 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) received 1, 5 and 10 \u00b5M omecamtiv mecarbil sequentially, while Group 2 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) received 100 \u00b5M sotalol followed by 5 \u00b5M omecamtiv mecarbil. In the atrial setup, Group 3 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) received 5 and 10 \u00b5M omecamtiv mecarbil, and Group 4 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) received isoproterenol\/acetylcholine (IsoACh) to increase atrial fibrillation (AF) susceptibility, followed by 5 \u00b5M omecamtiv mecarbil. Omecamtiv mecarbil alone shortened ventricular APD\n                    <jats:sub>90<\/jats:sub>\n                    and QT interval, increased dispersion of repolarization, and raised ventricular arrhythmia incidence. Sotalol prolonged APD\n                    <jats:sub>90<\/jats:sub>\n                    , QT interval, and dispersion, with a marked rise in VT episodes; additional omecamtiv mecarbil did not further prolong repolarization but increased arrhythmia susceptibility further. In the atrial setup, omecamtiv mecarbil alone prolonged conduction time and increased AF inducibility. Under IsoACh, which shortened atrial APD and refractoriness and increased AF episodes, additional omecamtiv mecarbil slowed atrial conduction and markedly suppressed AF. In summary, omecamtiv mecarbil was proarrhythmic at the ventricular level, particularly under reduced repolarization reserve, but showed antiarrhythmic effects in an IsoACh-induced AF model and proarrhythmic properties in the healthy atrium, indicating a substrate-dependent electrophysiological profile.\n                  <\/jats:p>","DOI":"10.1007\/s12012-026-10200-0","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:42:19Z","timestamp":1790610139000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Substrate-Dependent Pro- and Antiarrhythmic Action of Omecamtiv Mecarbil at the Ventricular and Atrial Level: Insights from a Langendorff-Perfused Rabbit Heart Model"],"prefix":"10.1007","volume":"26","author":[{"given":"Julian","family":"Wolfes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Wegner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Rath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Doldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerrit","family":"Frommeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Ellermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"36","key":"10200_CR1","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","volume":"42","author":"TA McDonagh","year":"2021","unstructured":"McDonagh, T. 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