{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:21:30Z","timestamp":1792466490429,"version":"4.5.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["716509 to D.A.P."],"award-info":[{"award-number":["716509 to D.A.P."]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Organization for Scientific Research","award":["91714336 to D.A.P."],"award-info":[{"award-number":["91714336 to D.A.P."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8\u201310 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvab294","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T12:12:09Z","timestamp":1631189529000},"page":"2293-2303","source":"Crossref","is-referenced-by-count":24,"title":["Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model"],"prefix":"10.1093","volume":"118","author":[{"given":"Emile C A","family":"Nyns","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC) , Albinusdreef 2, 2300 RC, Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1477-5432","authenticated-orcid":false,"given":"Tianyi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J","family":"Schalij","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC) , Albinusdreef 2, 2300 RC, Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-1797","authenticated-orcid":false,"given":"Thomas J","family":"van Brakel","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery , LUMC, Albinusdreef 2, 2300 RC, Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arti A","family":"Ramkisoensing","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC) , Albinusdreef 2, 2300 RC, Leiden , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microelectronics, Delft University of Technology , Mekelweg 4, 2628 CD, Delft , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4180-7033","authenticated-orcid":false,"given":"Ren\u00e9 H","family":"Poelma","sequence":"additional","affiliation":[{"name":"Department of Microelectronics, Delft University of Technology , Mekelweg 4, 2628 CD, Delft , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balazs","family":"\u00d6rd\u00f6g","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Cardiology, Department of Cardiology, Leiden University Medical Center (LUMC) , Albinusdreef 2, 2300 RC, Leiden , The 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