Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits
Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize...
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| description | Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize that transgenic long-QT type 1 (LQT1) rabbits lacking repolarizing IKs current may help to sensitively detect HERG/IKr-blocking properties of drugs.
Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed.
At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p |
| doi_str_mv | 10.1371/journal.pone.0107210 |
| format | Article |
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Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed.
At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p<0.05) and E-4031-induced %APD prolongation was more pronounced in LQT1 at LV base-lateral (0.01 µM, LQT1, +29.6 ± 10.6% vs. LMC, +19.1 ± 3.8%, p<0.05) and LV base-septal positions. Moreover, erythromycin significantly increased spatial APD dispersion only in LQT1 and increased triangulation only in LQT1 in LV base-septal and RV mid positions. Similarly, E-4031 increased triangulation only in LQT1 in LV apex and base-septal positions.
E-4031 and erythromycin prolonged APD and increased triangulation more pronouncedly in LQT1 than in LMC rabbits. Moreover, erythromycin increased APD dispersion only in LQT1, indicating that transgenic LQT1 rabbits could serve as sensitive model to detect HERG/IKr-blocking properties of drugs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0107210</identifier><identifier>PMID: 25244401</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Action potential ; Action Potentials - drug effects ; Action Potentials - physiology ; Analysis ; Animals ; Animals, Genetically Modified ; Antibiotics ; Arrhythmia ; Biology and Life Sciences ; Cardiac arrhythmia ; Dispersion ; Drugs ; Electrocardiography ; Erythromycin ; Erythromycin - pharmacology ; Erythromycin - therapeutic use ; Female ; Genetic engineering ; Heart - drug effects ; Heart - physiopathology ; Long QT Syndrome - drug therapy ; Long QT Syndrome - physiopathology ; Medicine and Health Sciences ; Mutation ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Potassium ; Prolongation ; Pyridines - pharmacology ; Pyridines - therapeutic use ; Rabbits ; Research and Analysis Methods ; Transgenic ; Triangulation ; Ventricle</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e107210-e107210</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Ziupa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Ziupa et al 2014 Ziupa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4f19c242a25a74ecab695929e7dce978cf34b8c84242d088ce7fde4adaf800743</citedby><cites>FETCH-LOGICAL-c692t-4f19c242a25a74ecab695929e7dce978cf34b8c84242d088ce7fde4adaf800743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170956/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170956/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25244401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cavalli, Andrea</contributor><creatorcontrib>Ziupa, David</creatorcontrib><creatorcontrib>Beck, Julia</creatorcontrib><creatorcontrib>Franke, Gerlind</creatorcontrib><creatorcontrib>Perez Feliz, Stefanie</creatorcontrib><creatorcontrib>Hartmann, Maximilian</creatorcontrib><creatorcontrib>Koren, Gideon</creatorcontrib><creatorcontrib>Zehender, Manfred</creatorcontrib><creatorcontrib>Bode, Christoph</creatorcontrib><creatorcontrib>Brunner, Michael</creatorcontrib><creatorcontrib>Odening, Katja E</creatorcontrib><title>Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize that transgenic long-QT type 1 (LQT1) rabbits lacking repolarizing IKs current may help to sensitively detect HERG/IKr-blocking properties of drugs.
Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed.
At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p<0.05) and E-4031-induced %APD prolongation was more pronounced in LQT1 at LV base-lateral (0.01 µM, LQT1, +29.6 ± 10.6% vs. LMC, +19.1 ± 3.8%, p<0.05) and LV base-septal positions. Moreover, erythromycin significantly increased spatial APD dispersion only in LQT1 and increased triangulation only in LQT1 in LV base-septal and RV mid positions. Similarly, E-4031 increased triangulation only in LQT1 in LV apex and base-septal positions.
E-4031 and erythromycin prolonged APD and increased triangulation more pronouncedly in LQT1 than in LMC rabbits. Moreover, erythromycin increased APD dispersion only in LQT1, indicating that transgenic LQT1 rabbits could serve as sensitive model to detect HERG/IKr-blocking properties of drugs.</description><subject>Action potential</subject><subject>Action Potentials - drug effects</subject><subject>Action Potentials - physiology</subject><subject>Analysis</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Antibiotics</subject><subject>Arrhythmia</subject><subject>Biology and Life Sciences</subject><subject>Cardiac arrhythmia</subject><subject>Dispersion</subject><subject>Drugs</subject><subject>Electrocardiography</subject><subject>Erythromycin</subject><subject>Erythromycin - pharmacology</subject><subject>Erythromycin - therapeutic use</subject><subject>Female</subject><subject>Genetic engineering</subject><subject>Heart - drug effects</subject><subject>Heart - physiopathology</subject><subject>Long QT Syndrome - drug therapy</subject><subject>Long QT Syndrome - physiopathology</subject><subject>Medicine and Health Sciences</subject><subject>Mutation</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Potassium</subject><subject>Prolongation</subject><subject>Pyridines - pharmacology</subject><subject>Pyridines - therapeutic use</subject><subject>Rabbits</subject><subject>Research and Analysis Methods</subject><subject>Transgenic</subject><subject>Triangulation</subject><subject>Ventricle</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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>eNqNk11vFCEUhidGY2v1HxglaWI0cVa-5uvGZFPXdpMmrbV6SxgGZqksrMAY92f4j2W622bX9MJwARye9wUOnCx7ieAEkQp9uHGDt9xMVs7KCUSwwgg-yg5RQ3BeYkge74wPsmch3EBYkLosn2YHuMCUUogOsz-X3lk3WCE7IJWSIgbgFDibXZ3mrXHih_QBzHIKCQLcJsav48K75VpoC5wF08tP70FY8ai5GSeg02GVNDqtjXz0mtt-MAlIkaSJntvQS6sFMM72-ZdrENcrCRDwvG11DM-zJ4qbIF9s-6Ps2-fZ9clZfn5xOj-ZnueibHDMqUKNwBRzXPCKSsHbsika3MiqE7KpaqEIbWtR08R0sK6FrFQnKe-4qiGsKDnKXm98V8YFts1mYKgoKSogqUdiviE6x2_Yyusl92vmuGa3Aed7xn3UwkjWqqpsSMFVW3W0k02NZEvbssCkLQWv2uT1cbvb0C5lOqJNiTB7pvsrVi9Y734xiirYFGUyeLs18O7nIENkSx2ENIZb6Ybbc5c1RpSShB7_gz58uy3V83QBbZVL-4rRlE0pqhEuSV0lavIAlVonl1qkr6d0iu8J3u0JEhPl79jzIQQ2_3r1_-zF9332zQ67kNzERXBmGP9V2AfpBhTeheCluk8ygmysnLtssLFy2LZykuzV7gPdi-5KhfwFh-QTgQ</recordid><startdate>20140922</startdate><enddate>20140922</enddate><creator>Ziupa, David</creator><creator>Beck, Julia</creator><creator>Franke, Gerlind</creator><creator>Perez Feliz, Stefanie</creator><creator>Hartmann, Maximilian</creator><creator>Koren, Gideon</creator><creator>Zehender, Manfred</creator><creator>Bode, Christoph</creator><creator>Brunner, Michael</creator><creator>Odening, Katja E</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>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></search><sort><creationdate>20140922</creationdate><title>Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits</title><author>Ziupa, David ; Beck, Julia ; Franke, Gerlind ; Perez Feliz, Stefanie ; Hartmann, Maximilian ; Koren, Gideon ; Zehender, Manfred ; Bode, Christoph ; Brunner, Michael ; Odening, Katja E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4f19c242a25a74ecab695929e7dce978cf34b8c84242d088ce7fde4adaf800743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Action potential</topic><topic>Action Potentials - drug effects</topic><topic>Action Potentials - physiology</topic><topic>Analysis</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Antibiotics</topic><topic>Arrhythmia</topic><topic>Biology and Life Sciences</topic><topic>Cardiac arrhythmia</topic><topic>Dispersion</topic><topic>Drugs</topic><topic>Electrocardiography</topic><topic>Erythromycin</topic><topic>Erythromycin - pharmacology</topic><topic>Erythromycin - therapeutic use</topic><topic>Female</topic><topic>Genetic engineering</topic><topic>Heart - drug effects</topic><topic>Heart - physiopathology</topic><topic>Long QT Syndrome - drug therapy</topic><topic>Long QT Syndrome - physiopathology</topic><topic>Medicine and Health Sciences</topic><topic>Mutation</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Potassium</topic><topic>Prolongation</topic><topic>Pyridines - pharmacology</topic><topic>Pyridines - therapeutic use</topic><topic>Rabbits</topic><topic>Research and Analysis Methods</topic><topic>Transgenic</topic><topic>Triangulation</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ziupa, David</creatorcontrib><creatorcontrib>Beck, Julia</creatorcontrib><creatorcontrib>Franke, Gerlind</creatorcontrib><creatorcontrib>Perez Feliz, Stefanie</creatorcontrib><creatorcontrib>Hartmann, Maximilian</creatorcontrib><creatorcontrib>Koren, Gideon</creatorcontrib><creatorcontrib>Zehender, Manfred</creatorcontrib><creatorcontrib>Bode, Christoph</creatorcontrib><creatorcontrib>Brunner, Michael</creatorcontrib><creatorcontrib>Odening, Katja E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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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>Ziupa, David</au><au>Beck, Julia</au><au>Franke, Gerlind</au><au>Perez Feliz, Stefanie</au><au>Hartmann, Maximilian</au><au>Koren, Gideon</au><au>Zehender, Manfred</au><au>Bode, Christoph</au><au>Brunner, Michael</au><au>Odening, Katja E</au><au>Cavalli, Andrea</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-22</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e107210</spage><epage>e107210</epage><pages>e107210-e107210</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize that transgenic long-QT type 1 (LQT1) rabbits lacking repolarizing IKs current may help to sensitively detect HERG/IKr-blocking properties of drugs.
Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed.
At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p<0.05) and E-4031-induced %APD prolongation was more pronounced in LQT1 at LV base-lateral (0.01 µM, LQT1, +29.6 ± 10.6% vs. LMC, +19.1 ± 3.8%, p<0.05) and LV base-septal positions. Moreover, erythromycin significantly increased spatial APD dispersion only in LQT1 and increased triangulation only in LQT1 in LV base-septal and RV mid positions. Similarly, E-4031 increased triangulation only in LQT1 in LV apex and base-septal positions.
E-4031 and erythromycin prolonged APD and increased triangulation more pronouncedly in LQT1 than in LMC rabbits. Moreover, erythromycin increased APD dispersion only in LQT1, indicating that transgenic LQT1 rabbits could serve as sensitive model to detect HERG/IKr-blocking properties of drugs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25244401</pmid><doi>10.1371/journal.pone.0107210</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-09, Vol.9 (9), p.e107210-e107210 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1564150384 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Action potential Action Potentials - drug effects Action Potentials - physiology Analysis Animals Animals, Genetically Modified Antibiotics Arrhythmia Biology and Life Sciences Cardiac arrhythmia Dispersion Drugs Electrocardiography Erythromycin Erythromycin - pharmacology Erythromycin - therapeutic use Female Genetic engineering Heart - drug effects Heart - physiopathology Long QT Syndrome - drug therapy Long QT Syndrome - physiopathology Medicine and Health Sciences Mutation Piperidines - pharmacology Piperidines - therapeutic use Potassium Prolongation Pyridines - pharmacology Pyridines - therapeutic use Rabbits Research and Analysis Methods Transgenic Triangulation Ventricle |
| title | Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T02%3A05%3A47IST&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=Pronounced%20effects%20of%20HERG-blockers%20E-4031%20and%20erythromycin%20on%20APD,%20spatial%20APD%20dispersion%20and%20triangulation%20in%20transgenic%20long-QT%20type%201%20rabbits&rft.jtitle=PloS%20one&rft.au=Ziupa,%20David&rft.date=2014-09-22&rft.volume=9&rft.issue=9&rft.spage=e107210&rft.epage=e107210&rft.pages=e107210-e107210&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0107210&rft_dat=%3Cgale_plos_%3EA418126387%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=1564150384&rft_id=info:pmid/25244401&rft_galeid=A418126387&rft_doaj_id=oai_doaj_org_article_bf76935afb7d4de981eb4b6523b6ca7b&rfr_iscdi=true |