Loading…
Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males
The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The pres...
Saved in:
| Published in: | Circulation (New York, N.Y.) N.Y.), 2002-10, Vol.106 (15), p.2004-2011 |
|---|---|
| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3 |
| container_end_page | 2011 |
| container_issue | 15 |
| container_start_page | 2004 |
| container_title | Circulation (New York, N.Y.) |
| container_volume | 106 |
| creator | DI DIEGO, José M CORDEIRO, Jonathan M GOODROW, Robert J FISH, Jeffrey M ZYGMUNT, Andrew C PEREZ, Guillermo J SCORNIK, Fabiana S ANTZELEVITCH, Charles |
| description | The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females.
We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8+/-2.0% of that of phase 2 in males compared with 73.8+/-4.4% in females (P |
| doi_str_mv | 10.1161/01.cir.0000032002.22105.7a |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72157952</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>72157952</sourcerecordid><originalsourceid>FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3</originalsourceid><addsrcrecordid>eNpdkFuL1DAUgIMo7rj6FyQs6FtrcpI0jW_r4GVgQRAF38Jpmrhd2mRMpg_z783sDgyYl5CT79w-Qm44aznv-AfGWzfllp2OAMagBeBMtRqfkQ1XIBuphHlONvXfNFoAXJFXpTzUZye0ekmuOAjNAPSG_N6lODmKcaTOz_M6Y6YDlqnQkDI93Hu6z35MyxQxOk9TeIx9yusfHJGWYxxzWip072M6HPeeTpEuOPvymrwIOBf_5nxfk19fPv_cfmvuvn_dbW_vGqcMOzQgB9MHdM5ACHqQ0HXDMAgphO6gC1Io7dToe2eMkiIMARG4MAi94aiCE9fk_VPdfU5_V18OdpnKaRWMPq3FauBKGwUVvPkPfEhrjnU2Cxy05H1_gj4-QS6nUrIPdp-nBfPRcmZP8i3jdrv7YS_y7aN8q29r8ttzh3VY_HhJPduuwLszgMXhHHJ1OpULJ4yWtZj4B-LrjQ4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>212741882</pqid></control><display><type>article</type><title>Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males</title><source>EZB Electronic Journals Library</source><creator>DI DIEGO, José M ; CORDEIRO, Jonathan M ; GOODROW, Robert J ; FISH, Jeffrey M ; ZYGMUNT, Andrew C ; PEREZ, Guillermo J ; SCORNIK, Fabiana S ; ANTZELEVITCH, Charles</creator><creatorcontrib>DI DIEGO, José M ; CORDEIRO, Jonathan M ; GOODROW, Robert J ; FISH, Jeffrey M ; ZYGMUNT, Andrew C ; PEREZ, Guillermo J ; SCORNIK, Fabiana S ; ANTZELEVITCH, Charles</creatorcontrib><description>The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females.
We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8+/-2.0% of that of phase 2 in males compared with 73.8+/-4.4% in females (P<0.05) at a cycle length of 2000 ms. I(to) density was 26% smaller and time constant for inactivation 17% smaller at +40 mV in female versus male RV epicardial cells (P<0.05). The other functional characteristics of I(to), including the voltage dependence of inactivation and time course of reactivation, were no different between the sexes. Pinacidil caused loss of action potential dome in male, but not female, RV epicardial tissue slices. Terfenadine (5 micromol/L) induced phase 2 reentry in 6 of 7 male but only 2 of 7 female arterially perfused wedge preparations. Two of 6 male and 1 of 2 female preparations developed polymorphic ventricular tachycardia/ventricular fibrillation.
Our results suggest that the predominance of the Brugada phenotype in males is a result of the presence of a more prominent I(to) in males versus females.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.0000032002.22105.7a</identifier><identifier>PMID: 12370227</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Action Potentials - drug effects ; Animals ; Arrhythmias, Cardiac - diagnosis ; Arrhythmias, Cardiac - etiology ; Arrhythmias, Cardiac - physiopathology ; Biological and medical sciences ; Cardiac dysrhythmias ; Cardiology. Vascular system ; Cells, Cultured ; Culture Techniques ; Dogs ; Female ; Heart ; Heart - physiology ; Kinetics ; Male ; Medical sciences ; Pericardium - drug effects ; Pericardium - physiology ; Phenotype ; Pinacidil - pharmacology ; Sex Factors ; Syndrome ; Terfenadine - pharmacology</subject><ispartof>Circulation (New York, N.Y.), 2002-10, Vol.106 (15), p.2004-2011</ispartof><rights>2002 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Oct 8, 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3</citedby><cites>FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13974210$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12370227$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DI DIEGO, José M</creatorcontrib><creatorcontrib>CORDEIRO, Jonathan M</creatorcontrib><creatorcontrib>GOODROW, Robert J</creatorcontrib><creatorcontrib>FISH, Jeffrey M</creatorcontrib><creatorcontrib>ZYGMUNT, Andrew C</creatorcontrib><creatorcontrib>PEREZ, Guillermo J</creatorcontrib><creatorcontrib>SCORNIK, Fabiana S</creatorcontrib><creatorcontrib>ANTZELEVITCH, Charles</creatorcontrib><title>Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females.
We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8+/-2.0% of that of phase 2 in males compared with 73.8+/-4.4% in females (P<0.05) at a cycle length of 2000 ms. I(to) density was 26% smaller and time constant for inactivation 17% smaller at +40 mV in female versus male RV epicardial cells (P<0.05). The other functional characteristics of I(to), including the voltage dependence of inactivation and time course of reactivation, were no different between the sexes. Pinacidil caused loss of action potential dome in male, but not female, RV epicardial tissue slices. Terfenadine (5 micromol/L) induced phase 2 reentry in 6 of 7 male but only 2 of 7 female arterially perfused wedge preparations. Two of 6 male and 1 of 2 female preparations developed polymorphic ventricular tachycardia/ventricular fibrillation.
Our results suggest that the predominance of the Brugada phenotype in males is a result of the presence of a more prominent I(to) in males versus females.</description><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>Arrhythmias, Cardiac - diagnosis</subject><subject>Arrhythmias, Cardiac - etiology</subject><subject>Arrhythmias, Cardiac - physiopathology</subject><subject>Biological and medical sciences</subject><subject>Cardiac dysrhythmias</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Culture Techniques</subject><subject>Dogs</subject><subject>Female</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pericardium - drug effects</subject><subject>Pericardium - physiology</subject><subject>Phenotype</subject><subject>Pinacidil - pharmacology</subject><subject>Sex Factors</subject><subject>Syndrome</subject><subject>Terfenadine - pharmacology</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNpdkFuL1DAUgIMo7rj6FyQs6FtrcpI0jW_r4GVgQRAF38Jpmrhd2mRMpg_z783sDgyYl5CT79w-Qm44aznv-AfGWzfllp2OAMagBeBMtRqfkQ1XIBuphHlONvXfNFoAXJFXpTzUZye0ekmuOAjNAPSG_N6lODmKcaTOz_M6Y6YDlqnQkDI93Hu6z35MyxQxOk9TeIx9yusfHJGWYxxzWip072M6HPeeTpEuOPvymrwIOBf_5nxfk19fPv_cfmvuvn_dbW_vGqcMOzQgB9MHdM5ACHqQ0HXDMAgphO6gC1Io7dToe2eMkiIMARG4MAi94aiCE9fk_VPdfU5_V18OdpnKaRWMPq3FauBKGwUVvPkPfEhrjnU2Cxy05H1_gj4-QS6nUrIPdp-nBfPRcmZP8i3jdrv7YS_y7aN8q29r8ttzh3VY_HhJPduuwLszgMXhHHJ1OpULJ4yWtZj4B-LrjQ4</recordid><startdate>20021008</startdate><enddate>20021008</enddate><creator>DI DIEGO, José M</creator><creator>CORDEIRO, Jonathan M</creator><creator>GOODROW, Robert J</creator><creator>FISH, Jeffrey M</creator><creator>ZYGMUNT, Andrew C</creator><creator>PEREZ, Guillermo J</creator><creator>SCORNIK, Fabiana S</creator><creator>ANTZELEVITCH, Charles</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20021008</creationdate><title>Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males</title><author>DI DIEGO, José M ; CORDEIRO, Jonathan M ; GOODROW, Robert J ; FISH, Jeffrey M ; ZYGMUNT, Andrew C ; PEREZ, Guillermo J ; SCORNIK, Fabiana S ; ANTZELEVITCH, Charles</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>Arrhythmias, Cardiac - diagnosis</topic><topic>Arrhythmias, Cardiac - etiology</topic><topic>Arrhythmias, Cardiac - physiopathology</topic><topic>Biological and medical sciences</topic><topic>Cardiac dysrhythmias</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Culture Techniques</topic><topic>Dogs</topic><topic>Female</topic><topic>Heart</topic><topic>Heart - physiology</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pericardium - drug effects</topic><topic>Pericardium - physiology</topic><topic>Phenotype</topic><topic>Pinacidil - pharmacology</topic><topic>Sex Factors</topic><topic>Syndrome</topic><topic>Terfenadine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>DI DIEGO, José M</creatorcontrib><creatorcontrib>CORDEIRO, Jonathan M</creatorcontrib><creatorcontrib>GOODROW, Robert J</creatorcontrib><creatorcontrib>FISH, Jeffrey M</creatorcontrib><creatorcontrib>ZYGMUNT, Andrew C</creatorcontrib><creatorcontrib>PEREZ, Guillermo J</creatorcontrib><creatorcontrib>SCORNIK, Fabiana S</creatorcontrib><creatorcontrib>ANTZELEVITCH, Charles</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>DI DIEGO, José M</au><au>CORDEIRO, Jonathan M</au><au>GOODROW, Robert J</au><au>FISH, Jeffrey M</au><au>ZYGMUNT, Andrew C</au><au>PEREZ, Guillermo J</au><au>SCORNIK, Fabiana S</au><au>ANTZELEVITCH, Charles</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2002-10-08</date><risdate>2002</risdate><volume>106</volume><issue>15</issue><spage>2004</spage><epage>2011</epage><pages>2004-2011</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The Brugada syndrome displays an autosomal dominant mode of transmission with low penetrance. Despite equal genetic transmission of the disease, the clinical phenotype is 8 to 10 times more prevalent in males than in females. The basis for this intriguing sex-related distinction is unknown. The present study tests the hypothesis that the disparity in expression of the Brugada phenotype is a result of a more prominent I(to)-mediated action potential notch in the right ventricular (RV) epicardium of males versus females.
We studied epicardial tissue slices, arterially perfused wedge preparations, and dissociated epicardial myocytes isolated from male and female canine hearts. RV epicardium action potential phase 1 amplitude was 64.8+/-2.0% of that of phase 2 in males compared with 73.8+/-4.4% in females (P<0.05) at a cycle length of 2000 ms. I(to) density was 26% smaller and time constant for inactivation 17% smaller at +40 mV in female versus male RV epicardial cells (P<0.05). The other functional characteristics of I(to), including the voltage dependence of inactivation and time course of reactivation, were no different between the sexes. Pinacidil caused loss of action potential dome in male, but not female, RV epicardial tissue slices. Terfenadine (5 micromol/L) induced phase 2 reentry in 6 of 7 male but only 2 of 7 female arterially perfused wedge preparations. Two of 6 male and 1 of 2 female preparations developed polymorphic ventricular tachycardia/ventricular fibrillation.
Our results suggest that the predominance of the Brugada phenotype in males is a result of the presence of a more prominent I(to) in males versus females.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>12370227</pmid><doi>10.1161/01.cir.0000032002.22105.7a</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2002-10, Vol.106 (15), p.2004-2011 |
| issn | 0009-7322 1524-4539 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72157952 |
| source | EZB Electronic Journals Library |
| subjects | Action Potentials - drug effects Animals Arrhythmias, Cardiac - diagnosis Arrhythmias, Cardiac - etiology Arrhythmias, Cardiac - physiopathology Biological and medical sciences Cardiac dysrhythmias Cardiology. Vascular system Cells, Cultured Culture Techniques Dogs Female Heart Heart - physiology Kinetics Male Medical sciences Pericardium - drug effects Pericardium - physiology Phenotype Pinacidil - pharmacology Sex Factors Syndrome Terfenadine - pharmacology |
| title | Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T19%3A48%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ionic%20and%20cellular%20basis%20for%20the%20predominance%20of%20the%20Brugada%20syndrome%20phenotype%20in%20males&rft.jtitle=Circulation%20(New%20York,%20N.Y.)&rft.au=DI%20DIEGO,%20Jos%C3%A9%20M&rft.date=2002-10-08&rft.volume=106&rft.issue=15&rft.spage=2004&rft.epage=2011&rft.pages=2004-2011&rft.issn=0009-7322&rft.eissn=1524-4539&rft.coden=CIRCAZ&rft_id=info:doi/10.1161/01.cir.0000032002.22105.7a&rft_dat=%3Cproquest_cross%3E72157952%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c590t-24b98facc92ff7b4266bbb34337626f4357c5de8c99543fbfaa2139a2891a5fc3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=212741882&rft_id=info:pmid/12370227&rfr_iscdi=true |