{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:22:55Z","timestamp":1789903375439,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["148401"],"award-info":[{"award-number":["148401"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","award":["G-16-00012708"],"award-info":[{"award-number":["G-16-00012708"]}],"id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7\u2009days): (i) Shams, instrumented but without tachypacing (n\u2009=\u20095); (ii) a placebo group, tachypaced while receiving placebo (n\u2009=\u20096); (iii) a control tachypacing group receiving nifedipine (10\u2009mg orally twice-daily; n\u2009=\u20095), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10\u2009mg orally twice-daily; n\u2009=\u20097), an N-\/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21\u2009days): (i) Shams, instrumented without tachypacing or drug therapy (n\u2009=\u20098); (ii) a placebo group, tachypaced while receiving placebo (n\u2009=\u20098); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10\u2009mg twice-daily; n\u2009=\u20098). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz136","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T15:16:54Z","timestamp":1558019814000},"page":"1975-1985","source":"Crossref","is-referenced-by-count":22,"title":["An N-\/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation"],"prefix":"10.1093","volume":"115","author":[{"given":"Kazuko","family":"Tajiri","sequence":"first","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"},{"name":"Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1\u20131\u20131 Tennodai, Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4696-7722","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Guichard","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"},{"name":"Department of Cardiology, University Hospital of Saint-\u00c9tienne, University Jean Monnet, Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Naud","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Tardif","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center, Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Belanger St E, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine Da","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Saint-\u00c9tienne, University Jean Monnet, Saint-\u00c9tienne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Aonuma","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1\u20131\u20131 Tennodai, Tsukuba, Ibaraki, 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