{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:33:54Z","timestamp":1780385634365,"version":"3.54.1"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,11,11]]},"abstract":"<jats:sec><jats:title><jats:underline>Rationale:<\/jats:underline><\/jats:title><jats:p>Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Objective:<\/jats:underline><\/jats:title><jats:p>We addressed the hypotheses that there is regional disease-related expression of K<jats:sub>ATP<\/jats:sub>channels in human cardiomyopathic hearts and that K<jats:sub>ATP<\/jats:sub>channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness.<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Methods and Results:<\/jats:underline><\/jats:title><jats:p>In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 \u03bcmol\/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K<jats:sub>ATP<\/jats:sub>subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (<jats:italic>P<\/jats:italic>=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (<jats:italic>P<\/jats:italic>=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K<jats:sub>ATP<\/jats:sub>subunit on the endocardium compared with the epicardium (<jats:italic>P<\/jats:italic>&lt;0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (\u0394ERP<jats:sub>Transmural<\/jats:sub>=ERP<jats:sub>Epicardium<\/jats:sub>\u2212ERP<jats:sub>Endocardium<\/jats:sub>) was verified with pacing protocols. \u0394ERP<jats:sub>Transmural<\/jats:sub>in control was 5\u00b12 ms and increased to 36\u00b15 ms with ischemia. This effect was greatly attenuated by glibenclamide (\u0394ERP<jats:sub>Transmural<\/jats:sub>for glibenclamide+ischemia=4.9\u00b14 ms,<jats:italic>P<\/jats:italic>=0.019 versus control ischemia).<\/jats:p><\/jats:sec><jats:sec><jats:title><jats:underline>Conclusions:<\/jats:underline><\/jats:title><jats:p>K<jats:sub>ATP<\/jats:sub>channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K<jats:sub>ATP<\/jats:sub>channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.<\/jats:p><\/jats:sec>","DOI":"10.1161\/circresaha.110.232918","type":"journal-article","created":{"date-parts":[[2011,10,7]],"date-time":"2011-10-07T06:23:58Z","timestamp":1317968638000},"page":"1309-1318","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Role of K<sub>ATP<\/sub>Channels in the Maintenance of Ventricular Fibrillation in Cardiomyopathic Human Hearts"],"prefix":"10.1161","volume":"109","author":[{"given":"Talha A.","family":"Farid","sequence":"first","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnakumar","family":"Nair","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steph\u00e9ne","family":"Mass\u00e9","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Ali","family":"Azam","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ange","family":"Maguy","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick F. 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Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay","family":"Chauhan","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Varr\u00f3","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Al-Hesayen","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menashe","family":"Waxman","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Nattel","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); Ryerson University, Toronto, Ontario, Canada (K.U.); St Michael's Hospital, Toronto, Ontario, Canada (P.D., A.A.-H.); Faculty of Medicine, University of Szeged, Hungary (A.V.); Montreal Heart Institute and Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada (A.M., S.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumaraswamy","family":"Nanthakumar","sequence":"additional","affiliation":[{"name":"From the University Health Network, Toronto, Ontario, Canada (T.A.F., K.N., S.M., M.A.A., F.H.L., K.U., V.C., M.W., K.N.); 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