Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis
Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and developmen...
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| creator | Adeyemi, Oladipupo Alvarez-Laviada, Anita Schultz, Francisca Ibrahim, Effendi Trauner, Michael Williamson, Catherine Glukhov, Alexey V Gorelik, Julia |
| description | Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.
High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
TC significantly prolonged the PR interval by 11.0±3.5% (P |
| doi_str_mv | 10.1371/journal.pone.0183167 |
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High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.
Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0183167</identifier><identifier>PMID: 28934223</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Analysis ; Animals ; Antiarrhythmia agents ; Arrhythmia ; Bile ; Biology and Life Sciences ; Calcium ; Calcium - pharmacology ; Calcium channels (L-type) ; Calcium channels (T-type) ; Calcium Channels, T-Type - metabolism ; Calcium currents ; Cardiac arrhythmia ; Cardiac muscle ; Cardiomyocytes ; Cholestasis ; Cholestasis - metabolism ; Cholestasis - physiopathology ; Cholestasis - prevention & control ; Complications and side effects ; Conduction ; Deoxycholic acid ; Developmental biology ; Dosage and administration ; EKG ; Electrophysiological Phenomena - drug effects ; Female ; Fetal Heart - drug effects ; Fetal Heart - metabolism ; Fetal Heart - physiopathology ; Fetuses ; Fluorescence ; Gallbladder diseases ; Heart ; Heart diseases ; Heart rate ; Heart Ventricles - drug effects ; Heart Ventricles - physiopathology ; Humans ; Lidocaine ; Medicine ; Medicine and Health Sciences ; Myocytes ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Neonates ; Nifedipine ; Perfusion ; Physical Sciences ; Pregnancy ; Prevention ; Prognosis ; Propagation ; Rats ; Risk factors ; Rodents ; Sodium ; Studies ; Taurocholic acid ; Taurocholic Acid - pharmacology ; Ursodeoxycholic acid ; Ursodeoxycholic Acid - pharmacology ; Velocity ; Ventricle ; Womens health</subject><ispartof>PloS one, 2017-09, Vol.12 (9), p.e0183167-e0183167</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c718t-cb39ce9ebf59eaabbfd5d472f7bd1f80ac7e129e2f76df908c1030b7c3f9bba83</citedby><cites>FETCH-LOGICAL-c718t-cb39ce9ebf59eaabbfd5d472f7bd1f80ac7e129e2f76df908c1030b7c3f9bba83</cites><orcidid>0000-0003-1148-9158</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608194/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608194/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28934223$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rodriguez-Ortigosa, Carlos M</contributor><creatorcontrib>Adeyemi, Oladipupo</creatorcontrib><creatorcontrib>Alvarez-Laviada, Anita</creatorcontrib><creatorcontrib>Schultz, Francisca</creatorcontrib><creatorcontrib>Ibrahim, Effendi</creatorcontrib><creatorcontrib>Trauner, Michael</creatorcontrib><creatorcontrib>Williamson, Catherine</creatorcontrib><creatorcontrib>Glukhov, Alexey V</creatorcontrib><creatorcontrib>Gorelik, Julia</creatorcontrib><title>Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description><![CDATA[Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.
High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.
Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.]]></description><subject>Acids</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antiarrhythmia agents</subject><subject>Arrhythmia</subject><subject>Bile</subject><subject>Biology and Life Sciences</subject><subject>Calcium</subject><subject>Calcium - pharmacology</subject><subject>Calcium channels (L-type)</subject><subject>Calcium channels (T-type)</subject><subject>Calcium Channels, T-Type - metabolism</subject><subject>Calcium currents</subject><subject>Cardiac arrhythmia</subject><subject>Cardiac muscle</subject><subject>Cardiomyocytes</subject><subject>Cholestasis</subject><subject>Cholestasis - metabolism</subject><subject>Cholestasis - physiopathology</subject><subject>Cholestasis - prevention & control</subject><subject>Complications and side effects</subject><subject>Conduction</subject><subject>Deoxycholic acid</subject><subject>Developmental biology</subject><subject>Dosage and administration</subject><subject>EKG</subject><subject>Electrophysiological Phenomena - drug effects</subject><subject>Female</subject><subject>Fetal Heart - drug effects</subject><subject>Fetal Heart - metabolism</subject><subject>Fetal Heart - physiopathology</subject><subject>Fetuses</subject><subject>Fluorescence</subject><subject>Gallbladder diseases</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart rate</subject><subject>Heart Ventricles - drug effects</subject><subject>Heart Ventricles - physiopathology</subject><subject>Humans</subject><subject>Lidocaine</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Myocytes</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Neonates</subject><subject>Nifedipine</subject><subject>Perfusion</subject><subject>Physical Sciences</subject><subject>Pregnancy</subject><subject>Prevention</subject><subject>Prognosis</subject><subject>Propagation</subject><subject>Rats</subject><subject>Risk factors</subject><subject>Rodents</subject><subject>Sodium</subject><subject>Studies</subject><subject>Taurocholic acid</subject><subject>Taurocholic Acid - pharmacology</subject><subject>Ursodeoxycholic acid</subject><subject>Ursodeoxycholic Acid - pharmacology</subject><subject>Velocity</subject><subject>Ventricle</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9tq3DAQhk1padK0b1BaQaG0F7uVLNuybgoh9LAQCLRJb4VOXivI1kay0uxD9J0r7zphXXJRDLIYffOP9EuTZa8RXCJM0KdrF33P7XLjer2EqMaoIk-yY0RxvqhyiJ8ezI-yFyFcQ1jiuqqeZ0d5TXGR5_g4-3Plg1Pa3W1l66yRgEujwMbrW90PAYyjNzJa7oF0vYpyMK4Hwbrfpl8D3ivAvW-3Q9sZDsQWeB0G58e1y8Ww3WgguZUmdkBG75MYMD1o9BCDDkDFHTgWTlk8mPAye9ZwG_Sr6X-SXX39cnn2fXF-8W11dnq-kATVw0IKTKWmWjQl1ZwL0ahSFSRviFCoqSGXRKOc6hSoVENhLRHEUBCJGyoEr_FJ9navu7EusMnJwBAtEM7LuigTsdoTyvFrtvGm437LHDdsF3B-zbgfjLSaEVoLSpAqqqIsCCwoF1UFaZrgVFKIpPV5qhZFp5UcPeV2Jjpf6U3L1u6WlRWs056SwIdJwLubmLxinQlSW8t77eJu33lVY4JxQt_9gz5-uola83QA0zcu1ZWjKDstYUnKEhOaqOUjVPqU7kx6DboxKT5L-DhLSMyg74Y1jyGw1c8f_89e_Jqz7w_YVnM7tMHZOL7FMAeLPSi9C8Hr5sFkBNnYNfdusLFr2NQ1Ke3N4QU9JN23Cf4LBTAW6g</recordid><startdate>20170921</startdate><enddate>20170921</enddate><creator>Adeyemi, Oladipupo</creator><creator>Alvarez-Laviada, Anita</creator><creator>Schultz, Francisca</creator><creator>Ibrahim, Effendi</creator><creator>Trauner, Michael</creator><creator>Williamson, Catherine</creator><creator>Glukhov, Alexey V</creator><creator>Gorelik, Julia</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1148-9158</orcidid></search><sort><creationdate>20170921</creationdate><title>Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis</title><author>Adeyemi, Oladipupo ; Alvarez-Laviada, Anita ; Schultz, Francisca ; Ibrahim, Effendi ; Trauner, Michael ; Williamson, Catherine ; Glukhov, Alexey V ; Gorelik, Julia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c718t-cb39ce9ebf59eaabbfd5d472f7bd1f80ac7e129e2f76df908c1030b7c3f9bba83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acids</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antiarrhythmia agents</topic><topic>Arrhythmia</topic><topic>Bile</topic><topic>Biology and Life Sciences</topic><topic>Calcium</topic><topic>Calcium - pharmacology</topic><topic>Calcium channels (L-type)</topic><topic>Calcium channels (T-type)</topic><topic>Calcium Channels, T-Type - metabolism</topic><topic>Calcium currents</topic><topic>Cardiac arrhythmia</topic><topic>Cardiac muscle</topic><topic>Cardiomyocytes</topic><topic>Cholestasis</topic><topic>Cholestasis - metabolism</topic><topic>Cholestasis - physiopathology</topic><topic>Cholestasis - prevention & control</topic><topic>Complications and side effects</topic><topic>Conduction</topic><topic>Deoxycholic acid</topic><topic>Developmental biology</topic><topic>Dosage and administration</topic><topic>EKG</topic><topic>Electrophysiological Phenomena - drug effects</topic><topic>Female</topic><topic>Fetal Heart - drug effects</topic><topic>Fetal Heart - metabolism</topic><topic>Fetal Heart - physiopathology</topic><topic>Fetuses</topic><topic>Fluorescence</topic><topic>Gallbladder diseases</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart rate</topic><topic>Heart Ventricles - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Adeyemi, Oladipupo</au><au>Alvarez-Laviada, Anita</au><au>Schultz, Francisca</au><au>Ibrahim, Effendi</au><au>Trauner, Michael</au><au>Williamson, Catherine</au><au>Glukhov, Alexey V</au><au>Gorelik, Julia</au><au>Rodriguez-Ortigosa, Carlos M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-09-21</date><risdate>2017</risdate><volume>12</volume><issue>9</issue><spage>e0183167</spage><epage>e0183167</epage><pages>e0183167-e0183167</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[Increased maternal serum bile acid concentrations in intrahepatic cholestasis of pregnancy (ICP) are associated with fetal cardiac arrhythmias. Ursodeoxycholic acid (UDCA) has been shown to demonstrate anti-arrhythmic properties via preventing ICP-associated cardiac conduction slowing and development of reentrant arrhythmias, although the cellular mechanism is still being elucidated.
High-resolution fluorescent optical mapping of electrical activity and electrocardiogram measurements were used to characterize effects of UDCA on one-day-old neonatal and adult female Langendorff-perfused rat hearts. ICP was modelled by perfusion of taurocholic acid (TC, 400μM). Whole-cell calcium currents were recorded from neonatal rat and human fetal cardiomyocytes.
TC significantly prolonged the PR interval by 11.0±3.5% (P<0.05) and slowed ventricular conduction velocity (CV) by 38.9±5.1% (P<0.05) exclusively in neonatal and not in maternal hearts. A similar CV decline was observed with the selective T-type calcium current (ICa,T) blocker mibefradil 1μM (23.0±6.2%, P<0.05), but not with the L-type calcium current (ICa,L) blocker nifedipine 1μM (6.9±6.6%, NS). The sodium channel blocker lidocaine (30μM) reduced CV by 60.4±4.5% (P<0.05). UDCA co-treatment was protective against CV slowing induced by TC and mibefradil, but not against lidocaine. UDCA prevented the TC-induced reduction in the ICa,T density in both isolated human fetal (-10.2±1.5 versus -5.5±0.9 pA/pF, P<0.05) and neonatal rat ventricular myocytes (-22.3±1.1 versus -9.6±0.8 pA/pF, P<0.0001), whereas UDCA had limited efficacy on the ICa,L.
Our findings demonstrate that ICa,T plays a significant role in ICP-associated fetal cardiac conduction slowing and arrhythmogenesis, and is an important component of the fetus-specific anti-arrhythmic activity of UDCA.]]></abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28934223</pmid><doi>10.1371/journal.pone.0183167</doi><tpages>e0183167</tpages><orcidid>https://orcid.org/0000-0003-1148-9158</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-09, Vol.12 (9), p.e0183167-e0183167 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1941325845 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Analysis Animals Antiarrhythmia agents Arrhythmia Bile Biology and Life Sciences Calcium Calcium - pharmacology Calcium channels (L-type) Calcium channels (T-type) Calcium Channels, T-Type - metabolism Calcium currents Cardiac arrhythmia Cardiac muscle Cardiomyocytes Cholestasis Cholestasis - metabolism Cholestasis - physiopathology Cholestasis - prevention & control Complications and side effects Conduction Deoxycholic acid Developmental biology Dosage and administration EKG Electrophysiological Phenomena - drug effects Female Fetal Heart - drug effects Fetal Heart - metabolism Fetal Heart - physiopathology Fetuses Fluorescence Gallbladder diseases Heart Heart diseases Heart rate Heart Ventricles - drug effects Heart Ventricles - physiopathology Humans Lidocaine Medicine Medicine and Health Sciences Myocytes Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Neonates Nifedipine Perfusion Physical Sciences Pregnancy Prevention Prognosis Propagation Rats Risk factors Rodents Sodium Studies Taurocholic acid Taurocholic Acid - pharmacology Ursodeoxycholic acid Ursodeoxycholic Acid - pharmacology Velocity Ventricle Womens health |
| title | Ursodeoxycholic acid prevents ventricular conduction slowing and arrhythmia by restoring T-type calcium current in fetuses during cholestasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T13%3A26%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ursodeoxycholic%20acid%20prevents%20ventricular%20conduction%20slowing%20and%20arrhythmia%20by%20restoring%20T-type%20calcium%20current%20in%20fetuses%20during%20cholestasis&rft.jtitle=PloS%20one&rft.au=Adeyemi,%20Oladipupo&rft.date=2017-09-21&rft.volume=12&rft.issue=9&rft.spage=e0183167&rft.epage=e0183167&rft.pages=e0183167-e0183167&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0183167&rft_dat=%3Cgale_plos_%3EA505755379%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1941325845&rft_id=info:pmid/28934223&rft_galeid=A505755379&rft_doaj_id=oai_doaj_org_article_798b971d464547049ab66090493b7cbb&rfr_iscdi=true |