{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:26:12Z","timestamp":1740137172760,"version":"3.37.3"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T00:00:00Z","timestamp":1391040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"AstraZeneca"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["6957","44365"],"award-info":[{"award-number":["6957","44365"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Effects of T\u2010Type Calcium Channel Blockade on AF<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The T\u2010type Ca<jats:sup>2+<\/jats:sup> channel (I<jats:sub>CaT<\/jats:sub>) blocker mibefradil prevents AF\u2010promoting remodeling occurring with atrial tachycardia, an action that has been attributed to I<jats:sub>CaT<\/jats:sub> inhibition. However, mibefradil has other effects, including ability to inhibit L\u2010type Ca<jats:sup>2+<\/jats:sup> channels, Na<jats:sup>+<\/jats:sup> channels and cytochromes. Thus, the relationship between I<jats:sub>CaT<\/jats:sub> inhibition and remodeling protection in AF is still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the effects of a novel highly selective Cav3 (I<jats:sub>CaT<\/jats:sub>) blocker, AZ9112, on atrial remodeling induced by 1\u2010week atrial tachypacing (AT\u2010P) in dogs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mongrel dogs were subjected to AT\u2010P at 400 bpm for 7\u00a0days, with atrioventricular\u2010node ablation and right\u2010ventricular demand pacing (80 bpm) to control ventricular rate. Four groups of dogs were studied in investigator\u2010blinded fashion: (1) a sham group, instrumented but without tachypacing or drug therapy (n\u00a0= 5); (2) a placebo group, tachypaced but receiving placebo (n\u00a0= 6); (3) a positive control tachypacing group receiving mibefradil (n\u00a0= 6); and (4) a test drug group, subjected to tachypacing during oral treatment with AZ9112 (n\u00a0= 8).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>One\u2010week AT\u2010P decreased atrial effective refractory period (ERP) at 6 of 8 sites and diminished rate\u2010dependent atrial ERP abbreviation. Mibefradil eliminated AT\u2010P\u2010induced ERP\u2010abbreviation at 4 of these 6 sites, while AZ9112 failed to affect ERP at any. Neither drug significantly affected AF vulnerability or AF duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>I<jats:sub>CaT<\/jats:sub> blockade with the highly selective compound AZ9112 failed to prevent rate\u2010related atrial remodeling. Thus, prevention of atrial electrophysiological remodeling by mibefradil cannot be attributed exclusively to I<jats:sub>CaT<\/jats:sub> blockade. These results indicate that I<jats:sub>CaT<\/jats:sub> inhibition is not likely to be a useful approach for AF therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.12346","type":"journal-article","created":{"date-parts":[[2013,12,13]],"date-time":"2013-12-13T22:04:40Z","timestamp":1386972280000},"page":"531-536","source":"Crossref","is-referenced-by-count":3,"title":["Inefficacy of a Highly Selective T\u2010Type Calcium Channel Blocker in Preventing Atrial Fibrillation Related Remodeling"],"prefix":"10.1111","volume":"25","author":[{"given":"TAKESHI","family":"KATO","sequence":"first","affiliation":[{"name":"Department of Medicine and Research Center Montreal Heart Institute University of Montreal  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YU\u2010KI","family":"IWASAKI","sequence":"additional","affiliation":[{"name":"Department of Medicine and Research Center Montreal Heart Institute University of Montreal  Montreal Quebec 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