Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy
Abstract Aims TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action...
Gespeichert in:
| Veröffentlicht in: | Cardiovascular research 2022-06, Vol.118 (7), p.1728-1741 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1741 |
|---|---|
| container_issue | 7 |
| container_start_page | 1728 |
| container_title | Cardiovascular research |
| container_volume | 118 |
| creator | Wiedmann, Felix Beyersdorf, Christoph Zhou, Xiao Bo Kraft, Manuel Paasche, Amelie Jávorszky, Natasa Rinné, Susanne Sutanto, Henry Büscher, Antonius Foerster, Kathrin I Blank, Antje El-Battrawy, Ibrahim Li, Xin Lang, Siegfried Tochtermann, Ursula Kremer, Jamila Arif, Rawa Karck, Matthias Decher, Niels van Loon, Gunther Akin, Ibrahim Borggrefe, Martin Kallenberger, Stefan Heijman, Jordi Haefeli, Walter E Katus, Hugo A Schmidt, Constanze |
| description | Abstract
Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.
Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.
Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Graphical Abstract
Graphical Abstract
Translational perspective
Pharmacological suppression of atrial TASK-1 potassium currents prolongs atrial refractoriness with no effects on ventricular repolarization, resulting in atrial-specific class-III antiarrhythmic effects. In our preclinical pilot study, the respiratory stimulant doxapram was successfully administered for cardioversion of acute AF as well as rhythm control of persistent AF in a clinically relevant porcine animal model. |
| doi_str_mv | 10.1093/cvr/cvab177 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2531533606</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/cvr/cvab177</oup_id><sourcerecordid>2531533606</sourcerecordid><originalsourceid>FETCH-LOGICAL-c357t-ed6238d60b53435ac6c938bf49bfdf58ac098672b5dc479a816c6b6b3bab2daf3</originalsourceid><addsrcrecordid>eNp9kD1PwzAQhi0EouVjYkeeEBIKOHHsJGxVxZeoxECZo7PjtEZJHGynpf8eQwsjw-l0p-de6R6EzmJyHZOC3siVDQUizrI9NI4zxiKapGwfjQkhecQppyN05Nx7GBnL0kM0oilJckbpGK3nVoFvVeexqTF4q6HBtRZWNw14bTq81n6JK_MJvYX2Fs8nr89RjHvjwTk9tFguoetUg3W31EL_nIDDgDuzCtt-CbYFaRqz0DJEO2_Bq8XmBB3U0Dh1uuvH6O3-bj59jGYvD0_TySySlGU-UhVPaF5xIhhNKQPJZUFzUaeFqKua5SBJkfMsEaySaVZAHnPJBRdUgEgqqOkxutzm9tZ8DMr5stVOqvBcp8zgyoTROIjghAf0aotKa5yzqi57q1uwmzIm5bfpMpgud6YDfb4LHkSrqj_2V20ALraAGfp_k74AMmaKUg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2531533606</pqid></control><display><type>article</type><title>Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Wiedmann, Felix ; Beyersdorf, Christoph ; Zhou, Xiao Bo ; Kraft, Manuel ; Paasche, Amelie ; Jávorszky, Natasa ; Rinné, Susanne ; Sutanto, Henry ; Büscher, Antonius ; Foerster, Kathrin I ; Blank, Antje ; El-Battrawy, Ibrahim ; Li, Xin ; Lang, Siegfried ; Tochtermann, Ursula ; Kremer, Jamila ; Arif, Rawa ; Karck, Matthias ; Decher, Niels ; van Loon, Gunther ; Akin, Ibrahim ; Borggrefe, Martin ; Kallenberger, Stefan ; Heijman, Jordi ; Haefeli, Walter E ; Katus, Hugo A ; Schmidt, Constanze</creator><creatorcontrib>Wiedmann, Felix ; Beyersdorf, Christoph ; Zhou, Xiao Bo ; Kraft, Manuel ; Paasche, Amelie ; Jávorszky, Natasa ; Rinné, Susanne ; Sutanto, Henry ; Büscher, Antonius ; Foerster, Kathrin I ; Blank, Antje ; El-Battrawy, Ibrahim ; Li, Xin ; Lang, Siegfried ; Tochtermann, Ursula ; Kremer, Jamila ; Arif, Rawa ; Karck, Matthias ; Decher, Niels ; van Loon, Gunther ; Akin, Ibrahim ; Borggrefe, Martin ; Kallenberger, Stefan ; Heijman, Jordi ; Haefeli, Walter E ; Katus, Hugo A ; Schmidt, Constanze</creatorcontrib><description>Abstract
Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.
Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.
Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Graphical Abstract
Graphical Abstract
Translational perspective
Pharmacological suppression of atrial TASK-1 potassium currents prolongs atrial refractoriness with no effects on ventricular repolarization, resulting in atrial-specific class-III antiarrhythmic effects. In our preclinical pilot study, the respiratory stimulant doxapram was successfully administered for cardioversion of acute AF as well as rhythm control of persistent AF in a clinically relevant porcine animal model.</description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvab177</identifier><identifier>PMID: 34028533</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><ispartof>Cardiovascular research, 2022-06, Vol.118 (7), p.1728-1741</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-ed6238d60b53435ac6c938bf49bfdf58ac098672b5dc479a816c6b6b3bab2daf3</citedby><cites>FETCH-LOGICAL-c357t-ed6238d60b53435ac6c938bf49bfdf58ac098672b5dc479a816c6b6b3bab2daf3</cites><orcidid>0000-0003-3783-0246 ; 0000-0001-5897-237X ; 0000-0002-1418-108X ; 0000-0001-8583-7181 ; 0000-0001-8168-0025 ; 0000-0001-8743-5194 ; 0000-0003-0672-6876 ; 0000-0002-5730-2013</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34028533$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wiedmann, Felix</creatorcontrib><creatorcontrib>Beyersdorf, Christoph</creatorcontrib><creatorcontrib>Zhou, Xiao Bo</creatorcontrib><creatorcontrib>Kraft, Manuel</creatorcontrib><creatorcontrib>Paasche, Amelie</creatorcontrib><creatorcontrib>Jávorszky, Natasa</creatorcontrib><creatorcontrib>Rinné, Susanne</creatorcontrib><creatorcontrib>Sutanto, Henry</creatorcontrib><creatorcontrib>Büscher, Antonius</creatorcontrib><creatorcontrib>Foerster, Kathrin I</creatorcontrib><creatorcontrib>Blank, Antje</creatorcontrib><creatorcontrib>El-Battrawy, Ibrahim</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Lang, Siegfried</creatorcontrib><creatorcontrib>Tochtermann, Ursula</creatorcontrib><creatorcontrib>Kremer, Jamila</creatorcontrib><creatorcontrib>Arif, Rawa</creatorcontrib><creatorcontrib>Karck, Matthias</creatorcontrib><creatorcontrib>Decher, Niels</creatorcontrib><creatorcontrib>van Loon, Gunther</creatorcontrib><creatorcontrib>Akin, Ibrahim</creatorcontrib><creatorcontrib>Borggrefe, Martin</creatorcontrib><creatorcontrib>Kallenberger, Stefan</creatorcontrib><creatorcontrib>Heijman, Jordi</creatorcontrib><creatorcontrib>Haefeli, Walter E</creatorcontrib><creatorcontrib>Katus, Hugo A</creatorcontrib><creatorcontrib>Schmidt, Constanze</creatorcontrib><title>Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>Abstract
Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.
Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.
Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Graphical Abstract
Graphical Abstract
Translational perspective
Pharmacological suppression of atrial TASK-1 potassium currents prolongs atrial refractoriness with no effects on ventricular repolarization, resulting in atrial-specific class-III antiarrhythmic effects. In our preclinical pilot study, the respiratory stimulant doxapram was successfully administered for cardioversion of acute AF as well as rhythm control of persistent AF in a clinically relevant porcine animal model.</description><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kD1PwzAQhi0EouVjYkeeEBIKOHHsJGxVxZeoxECZo7PjtEZJHGynpf8eQwsjw-l0p-de6R6EzmJyHZOC3siVDQUizrI9NI4zxiKapGwfjQkhecQppyN05Nx7GBnL0kM0oilJckbpGK3nVoFvVeexqTF4q6HBtRZWNw14bTq81n6JK_MJvYX2Fs8nr89RjHvjwTk9tFguoetUg3W31EL_nIDDgDuzCtt-CbYFaRqz0DJEO2_Bq8XmBB3U0Dh1uuvH6O3-bj59jGYvD0_TySySlGU-UhVPaF5xIhhNKQPJZUFzUaeFqKua5SBJkfMsEaySaVZAHnPJBRdUgEgqqOkxutzm9tZ8DMr5stVOqvBcp8zgyoTROIjghAf0aotKa5yzqi57q1uwmzIm5bfpMpgud6YDfb4LHkSrqj_2V20ALraAGfp_k74AMmaKUg</recordid><startdate>20220622</startdate><enddate>20220622</enddate><creator>Wiedmann, Felix</creator><creator>Beyersdorf, Christoph</creator><creator>Zhou, Xiao Bo</creator><creator>Kraft, Manuel</creator><creator>Paasche, Amelie</creator><creator>Jávorszky, Natasa</creator><creator>Rinné, Susanne</creator><creator>Sutanto, Henry</creator><creator>Büscher, Antonius</creator><creator>Foerster, Kathrin I</creator><creator>Blank, Antje</creator><creator>El-Battrawy, Ibrahim</creator><creator>Li, Xin</creator><creator>Lang, Siegfried</creator><creator>Tochtermann, Ursula</creator><creator>Kremer, Jamila</creator><creator>Arif, Rawa</creator><creator>Karck, Matthias</creator><creator>Decher, Niels</creator><creator>van Loon, Gunther</creator><creator>Akin, Ibrahim</creator><creator>Borggrefe, Martin</creator><creator>Kallenberger, Stefan</creator><creator>Heijman, Jordi</creator><creator>Haefeli, Walter E</creator><creator>Katus, Hugo A</creator><creator>Schmidt, Constanze</creator><general>Oxford University Press</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3783-0246</orcidid><orcidid>https://orcid.org/0000-0001-5897-237X</orcidid><orcidid>https://orcid.org/0000-0002-1418-108X</orcidid><orcidid>https://orcid.org/0000-0001-8583-7181</orcidid><orcidid>https://orcid.org/0000-0001-8168-0025</orcidid><orcidid>https://orcid.org/0000-0001-8743-5194</orcidid><orcidid>https://orcid.org/0000-0003-0672-6876</orcidid><orcidid>https://orcid.org/0000-0002-5730-2013</orcidid></search><sort><creationdate>20220622</creationdate><title>Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy</title><author>Wiedmann, Felix ; Beyersdorf, Christoph ; Zhou, Xiao Bo ; Kraft, Manuel ; Paasche, Amelie ; Jávorszky, Natasa ; Rinné, Susanne ; Sutanto, Henry ; Büscher, Antonius ; Foerster, Kathrin I ; Blank, Antje ; El-Battrawy, Ibrahim ; Li, Xin ; Lang, Siegfried ; Tochtermann, Ursula ; Kremer, Jamila ; Arif, Rawa ; Karck, Matthias ; Decher, Niels ; van Loon, Gunther ; Akin, Ibrahim ; Borggrefe, Martin ; Kallenberger, Stefan ; Heijman, Jordi ; Haefeli, Walter E ; Katus, Hugo A ; Schmidt, Constanze</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-ed6238d60b53435ac6c938bf49bfdf58ac098672b5dc479a816c6b6b3bab2daf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wiedmann, Felix</creatorcontrib><creatorcontrib>Beyersdorf, Christoph</creatorcontrib><creatorcontrib>Zhou, Xiao Bo</creatorcontrib><creatorcontrib>Kraft, Manuel</creatorcontrib><creatorcontrib>Paasche, Amelie</creatorcontrib><creatorcontrib>Jávorszky, Natasa</creatorcontrib><creatorcontrib>Rinné, Susanne</creatorcontrib><creatorcontrib>Sutanto, Henry</creatorcontrib><creatorcontrib>Büscher, Antonius</creatorcontrib><creatorcontrib>Foerster, Kathrin I</creatorcontrib><creatorcontrib>Blank, Antje</creatorcontrib><creatorcontrib>El-Battrawy, Ibrahim</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Lang, Siegfried</creatorcontrib><creatorcontrib>Tochtermann, Ursula</creatorcontrib><creatorcontrib>Kremer, Jamila</creatorcontrib><creatorcontrib>Arif, Rawa</creatorcontrib><creatorcontrib>Karck, Matthias</creatorcontrib><creatorcontrib>Decher, Niels</creatorcontrib><creatorcontrib>van Loon, Gunther</creatorcontrib><creatorcontrib>Akin, Ibrahim</creatorcontrib><creatorcontrib>Borggrefe, Martin</creatorcontrib><creatorcontrib>Kallenberger, Stefan</creatorcontrib><creatorcontrib>Heijman, Jordi</creatorcontrib><creatorcontrib>Haefeli, Walter E</creatorcontrib><creatorcontrib>Katus, Hugo A</creatorcontrib><creatorcontrib>Schmidt, Constanze</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wiedmann, Felix</au><au>Beyersdorf, Christoph</au><au>Zhou, Xiao Bo</au><au>Kraft, Manuel</au><au>Paasche, Amelie</au><au>Jávorszky, Natasa</au><au>Rinné, Susanne</au><au>Sutanto, Henry</au><au>Büscher, Antonius</au><au>Foerster, Kathrin I</au><au>Blank, Antje</au><au>El-Battrawy, Ibrahim</au><au>Li, Xin</au><au>Lang, Siegfried</au><au>Tochtermann, Ursula</au><au>Kremer, Jamila</au><au>Arif, Rawa</au><au>Karck, Matthias</au><au>Decher, Niels</au><au>van Loon, Gunther</au><au>Akin, Ibrahim</au><au>Borggrefe, Martin</au><au>Kallenberger, Stefan</au><au>Heijman, Jordi</au><au>Haefeli, Walter E</au><au>Katus, Hugo A</au><au>Schmidt, Constanze</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2022-06-22</date><risdate>2022</risdate><volume>118</volume><issue>7</issue><spage>1728</spage><epage>1741</epage><pages>1728-1741</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><abstract>Abstract
Aims
TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF.
Methods and results
Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram.
Conclusion
Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients.
Graphical Abstract
Graphical Abstract
Translational perspective
Pharmacological suppression of atrial TASK-1 potassium currents prolongs atrial refractoriness with no effects on ventricular repolarization, resulting in atrial-specific class-III antiarrhythmic effects. In our preclinical pilot study, the respiratory stimulant doxapram was successfully administered for cardioversion of acute AF as well as rhythm control of persistent AF in a clinically relevant porcine animal model.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34028533</pmid><doi>10.1093/cvr/cvab177</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-3783-0246</orcidid><orcidid>https://orcid.org/0000-0001-5897-237X</orcidid><orcidid>https://orcid.org/0000-0002-1418-108X</orcidid><orcidid>https://orcid.org/0000-0001-8583-7181</orcidid><orcidid>https://orcid.org/0000-0001-8168-0025</orcidid><orcidid>https://orcid.org/0000-0001-8743-5194</orcidid><orcidid>https://orcid.org/0000-0003-0672-6876</orcidid><orcidid>https://orcid.org/0000-0002-5730-2013</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-6363 |
| ispartof | Cardiovascular research, 2022-06, Vol.118 (7), p.1728-1741 |
| issn | 0008-6363 1755-3245 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2531533606 |
| source | Oxford University Press Journals All Titles (1996-Current); Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| title | Treatment of atrial fibrillation with doxapram: TASK-1 potassium channel inhibition as a novel pharmacological strategy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T23%3A42%3A45IST&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=Treatment%20of%20atrial%20fibrillation%20with%20doxapram:%20TASK-1%20potassium%20channel%20inhibition%20as%20a%20novel%20pharmacological%20strategy&rft.jtitle=Cardiovascular%20research&rft.au=Wiedmann,%20Felix&rft.date=2022-06-22&rft.volume=118&rft.issue=7&rft.spage=1728&rft.epage=1741&rft.pages=1728-1741&rft.issn=0008-6363&rft.eissn=1755-3245&rft_id=info:doi/10.1093/cvr/cvab177&rft_dat=%3Cproquest_cross%3E2531533606%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2531533606&rft_id=info:pmid/34028533&rft_oup_id=10.1093/cvr/cvab177&rfr_iscdi=true |