{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:06:54Z","timestamp":1791198414252,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2007,11,9]]},"abstract":"<jats:p>\n            Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, polymorphic VT, and ventricular fibrillation. Catecholaminergic polymorphic VT is caused by enhanced Ca\n            <jats:sup>2+<\/jats:sup>\n            release through defective ryanodine receptor (RyR2) channels. We used epicardial and endocardial optical mapping, chemical subendocardial ablation with Lugol\u2019s solution, and patch clamping in a knockin (RyR2\/RyR2\n            <jats:sup>R4496C<\/jats:sup>\n            ) mouse model to investigate the arrhythmogenic mechanisms in catecholaminergic polymorphic VT. In isolated hearts, spontaneous ventricular arrhythmias occurred in 54% of 13 RyR2\/RyR2\n            <jats:sup>R4496C<\/jats:sup>\n            and in 9% of 11 wild-type (\n            <jats:italic>P<\/jats:italic>\n            =0.03) littermates perfused with Ca\n            <jats:sup>2+<\/jats:sup>\n            and isoproterenol; 66% of 12 RyR2\/RyR2\n            <jats:sup>R4496C<\/jats:sup>\n            and 20% of 10 wild-type hearts perfused with caffeine and epinephrine showed arrhythmias (\n            <jats:italic>P<\/jats:italic>\n            =0.04). Epicardial mapping showed that monomorphic VT, bidirectional VT, and polymorphic VT manifested as concentric epicardial breakthrough patterns, suggesting a focal origin in the His\u2013Purkinje networks of either or both ventricles. Monomorphic VT was clearly unifocal, whereas bidirectional VT was bifocal. Polymorphic VT was initially multifocal but eventually became reentrant and degenerated into ventricular fibrillation. Endocardial mapping confirmed the Purkinje fiber origin of the focal arrhythmias. Chemical ablation of the right ventricular endocardial cavity with Lugol\u2019s solution induced complete right bundle branch block and converted the bidirectional VT into monomorphic VT in 4 anesthetized RyR2\/RyR2\n            <jats:sup>R4496C<\/jats:sup>\n            mice. Under current clamp, single Purkinje cells from RyR2\/RyR2\n            <jats:sup>R4496C<\/jats:sup>\n            mouse hearts generated delayed afterdepolarization\u2013induced triggered activity at lower frequencies and level of adrenergic stimulation than wild-type. Overall, the data demonstrate that the His\u2013Purkinje system is an important source of focal arrhythmias in catecholaminergic polymorphic VT.\n          <\/jats:p>","DOI":"10.1161\/circresaha.107.148064","type":"journal-article","created":{"date-parts":[[2007,9,14]],"date-time":"2007-09-14T01:49:05Z","timestamp":1189734545000},"page":"1039-1048","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":257,"title":["Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia"],"prefix":"10.1161","volume":"101","author":[{"given":"Marina","family":"Cerrone","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami F.","family":"Noujaim","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena G.","family":"Tolkacheva","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadzi","family":"Talkachou","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer","family":"Berenfeld","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Anumonwo","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep V.","family":"Pandit","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Vikstrom","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Napolitano","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia G.","family":"Priori","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301","family":"Jalife","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Institute for Cardiovascular Research (M.C., S.F.N., E.G.T., A.T., R.O\u2019C., O.B., J.A., S.V.P., K.V., J.J.), State University of New York, Upstate Medical University, Syracuse; and Molecular Cardiology (C.N., S.G.P.), Istituti di Ricovero e Cura a Carattere Scientifico Fondazione Maugeri, Pavia, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.5.1512"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.2.196"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000020013.73106.d8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000169067.51055.72"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000235869.50747.e1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.87.10.929"},{"key":"e_1_3_3_7_2","first-page":"990","volume":"280","year":"2004","unstructured":"Chuck ET, Meyers K, France D, Creazzo TL, Morley GE. Transitions in ventricular activation revealed by two-dimensional optical mapping. Anat Rec A Discov Mol Cell Evol Biol. 2004; 280: 990\u20131000.","journal-title":"Anat Rec A Discov Mol Cell Evol Biol"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.104.527325"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8167.1999.tb00192.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.89.12.1216"},{"key":"e_1_3_3_11_2","first-page":"S303","volume":"3","year":"2006","unstructured":"Tolkacheva EG, Vaidyanathan R, Munoz V, Noujaim S, Anumonwo J. Inward rectifier current properties of isolated murine Purkinje cells. Heart Rhythm. 2006; 3: S303 Abstract.","journal-title":"Heart Rhythm"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.41.6.899"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.7.5.753"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.166295"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.87.1.8419011"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1995.269.6.H1998"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.74.3.3742762"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000028455.36940.5e"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402388101"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02256119"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1302.012"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1540-8159.1989.tb01905.x"},{"key":"e_1_3_3_23_2","first-page":"199","volume":"9","year":"1922","unstructured":"Schwensen C. Ventricular Tachycardia as the result of the administration of digitalis. Heart. 1922; 9: 199\u2013204.","journal-title":"Heart"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.48.1.32"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.104.479295"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.107.148064","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:22:49Z","timestamp":1715570569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.107.148064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,9]]},"references-count":25,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,11,9]]}},"alternative-id":["10.1161\/CIRCRESAHA.107.148064"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.107.148064","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11,9]]},"assertion":[{"value":"2007-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}