{"doi":"10.1093/cvr/cvab177","title":"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 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.","journal":"Cardiovascular Research","year":2021,"id":156950,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":662950,"name":"Christoph Beyersdorf","orcid":"0000-0003-3975-6764","position":1,"is_corresponding":false},{"id":663970,"name":"Xiao Bo Zhou","orcid":null,"position":2,"is_corresponding":false},{"id":662951,"name":"Manuel Kraft","orcid":"0000-0001-6764-2970","position":3,"is_corresponding":false},{"id":662952,"name":"A Paasche","orcid":"0000-0001-6882-1428","position":4,"is_corresponding":false},{"id":663971,"name":"Natasa Jávorszky","orcid":null,"position":5,"is_corresponding":false},{"id":662953,"name":"Susanne Rinné","orcid":"0000-0003-2326-7069","position":6,"is_corresponding":false},{"id":270325,"name":"Henry Sutanto","orcid":"0000-0002-5730-2013","position":7,"is_corresponding":false},{"id":662954,"name":"Antonius Büscher","orcid":"0000-0003-1774-4252","position":8,"is_corresponding":false},{"id":662955,"name":"Kathrin I. Foerster","orcid":"0000-0001-8583-7181","position":9,"is_corresponding":false},{"id":662956,"name":"Antje Blank","orcid":"0000-0001-8743-5194","position":10,"is_corresponding":false},{"id":662957,"name":"Ibrahim El‐Battrawy","orcid":"0000-0002-0139-1045","position":11,"is_corresponding":false},{"id":662958,"name":"Xin Li","orcid":"0000-0002-4018-6220","position":12,"is_corresponding":false},{"id":663972,"name":"Siegfried Lang","orcid":null,"position":13,"is_corresponding":false},{"id":663973,"name":"U. Tochtermann","orcid":null,"position":14,"is_corresponding":false},{"id":662959,"name":"Jamila Kremer","orcid":"0000-0002-4660-6660","position":15,"is_corresponding":false},{"id":662960,"name":"Rawa Arif","orcid":"0009-0002-0158-2789","position":16,"is_corresponding":false},{"id":663974,"name":"Matthias Karck","orcid":null,"position":17,"is_corresponding":false},{"id":662961,"name":"Niels Decher","orcid":"0000-0002-9433-687X","position":18,"is_corresponding":false},{"id":662962,"name":"Gunther van Loon","orcid":"0000-0001-5191-5241","position":19,"is_corresponding":false},{"id":662963,"name":"İbrahim Akın","orcid":"0000-0003-1974-6147","position":20,"is_corresponding":false},{"id":662964,"name":"Martin Borggrefe","orcid":"0000-0002-3206-934X","position":21,"is_corresponding":false},{"id":251301,"name":"Stefan M. Kallenberger","orcid":"0000-0003-3783-0246","position":22,"is_corresponding":false},{"id":270328,"name":"Jordi Heijman","orcid":"0000-0002-1418-108X","position":23,"is_corresponding":false},{"id":612933,"name":"Walter E. Haefeli","orcid":"0000-0003-0672-6876","position":24,"is_corresponding":false},{"id":50056,"name":"Hugo A. Katus","orcid":"0000-0002-2293-2314","position":25,"is_corresponding":false},{"id":75480,"name":"Constanze Schmidt","orcid":"0000-0001-5897-237X","position":26,"is_corresponding":false},{"id":75472,"name":"Felix Wiedmann","orcid":"0000-0001-8168-0025","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:44:17.471040Z","pmid":"34028533","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}