Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study
Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to...
Gespeichert in:
| Veröffentlicht in: | Heart rhythm 2016-12, Vol.13 (12), p.2358-2365 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2365 |
|---|---|
| container_issue | 12 |
| container_start_page | 2358 |
| container_title | Heart rhythm |
| container_volume | 13 |
| creator | Liberos, Alejandro, PhD Bueno-Orovio, Alfonso, PhD Rodrigo, Miguel, MS Ravens, Ursula, MD Hernandez-Romero, Ismael, MS Fernandez-Aviles, Francisco, MD, PhD Guillem, Maria S., PhD Rodriguez, Blanca, PhD Climent, Andreu M., PhD |
| description | Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. Methods A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. Results Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL ( P |
| doi_str_mv | 10.1016/j.hrthm.2016.08.028 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5221730</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S1547527116306713</els_id><sourcerecordid>1_s2_0_S1547527116306713</sourcerecordid><originalsourceid>FETCH-LOGICAL-c514t-d0efdd7507060a0c48f327fda46a24f4f4e167bd7bf2f806c511de0d678a943d3</originalsourceid><addsrcrecordid>eNqFUtGK1TAQDaK46-oXCJIfaHeStEmv4MK6uCos-KA-hzRJ96am6ZKkV_oN_rTpXl3UF8lDzjBzzjBzBqGXBGoChJ-P9T7m_VTTEtTQ1UC7R-iUtC2vWCfI4w03omqpICfoWUojAN1xYE_RCRUt3zUNO0U_3iqvgra4t_m7tQGn2bhlwioYrJXXG9ZLjDbkhJdgbPSrC7dY7-McnMYqR6c8HlwfnfcquzngbOPkwj1-jS8DdkXVeafngkouLf1odcYHVah9SeQVp7yY9Tl6Miif7Itf_xn6ev3uy9WH6ubT-49XlzeVbkmTKwN2MEa0IICDAt10A6NiMKrhijZDeZZw0RvRD3TogBcWMRYMF53aNcywM3Rx1L1b-skaXWaLysu76CYVVzkrJ__OBLeXt_NBtpQSwaAIsKOAjnNK0Q4PXAJy80aO8t4buXkjoZPFm8J69WfbB85vM0rBm2OBLcMfnI0yaWeLOcbFsjBpZvefBhf_8LV3xSTlv9nVpnFeYih7lUQmKkF-3s5juw7CGXBBGPsJn6e8Og</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Liberos, Alejandro, PhD ; Bueno-Orovio, Alfonso, PhD ; Rodrigo, Miguel, MS ; Ravens, Ursula, MD ; Hernandez-Romero, Ismael, MS ; Fernandez-Aviles, Francisco, MD, PhD ; Guillem, Maria S., PhD ; Rodriguez, Blanca, PhD ; Climent, Andreu M., PhD</creator><creatorcontrib>Liberos, Alejandro, PhD ; Bueno-Orovio, Alfonso, PhD ; Rodrigo, Miguel, MS ; Ravens, Ursula, MD ; Hernandez-Romero, Ismael, MS ; Fernandez-Aviles, Francisco, MD, PhD ; Guillem, Maria S., PhD ; Rodriguez, Blanca, PhD ; Climent, Andreu M., PhD</creatorcontrib><description>Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. Methods A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. Results Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL ( P <.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2 ) and presented an increased efficacy in models with a depressed INa ( P <.01). Conclusion Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.</description><identifier>ISSN: 1547-5271</identifier><identifier>EISSN: 1556-3871</identifier><identifier>DOI: 10.1016/j.hrthm.2016.08.028</identifier><identifier>PMID: 27569443</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Action Potentials - physiology ; Anti-Arrhythmia Agents - pharmacology ; Atrial fibrillation ; Atrial Fibrillation - diagnosis ; Atrial Fibrillation - drug therapy ; Atrial Fibrillation - metabolism ; Atrial Fibrillation - physiopathology ; Atrial Remodeling ; Calcium Channels - metabolism ; Calcium current ; Cardiovascular ; Computer Simulation ; Humans ; Ionic currents ; Mathematical modeling ; Models, Cardiovascular ; Rotor dynamics ; Sodium Channels - metabolism</subject><ispartof>Heart rhythm, 2016-12, Vol.13 (12), p.2358-2365</ispartof><rights>The Authors</rights><rights>2016 The Authors</rights><rights>Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2016 The Authors 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-d0efdd7507060a0c48f327fda46a24f4f4e167bd7bf2f806c511de0d678a943d3</citedby><cites>FETCH-LOGICAL-c514t-d0efdd7507060a0c48f327fda46a24f4f4e167bd7bf2f806c511de0d678a943d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.hrthm.2016.08.028$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27569443$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liberos, Alejandro, PhD</creatorcontrib><creatorcontrib>Bueno-Orovio, Alfonso, PhD</creatorcontrib><creatorcontrib>Rodrigo, Miguel, MS</creatorcontrib><creatorcontrib>Ravens, Ursula, MD</creatorcontrib><creatorcontrib>Hernandez-Romero, Ismael, MS</creatorcontrib><creatorcontrib>Fernandez-Aviles, Francisco, MD, PhD</creatorcontrib><creatorcontrib>Guillem, Maria S., PhD</creatorcontrib><creatorcontrib>Rodriguez, Blanca, PhD</creatorcontrib><creatorcontrib>Climent, Andreu M., PhD</creatorcontrib><title>Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study</title><title>Heart rhythm</title><addtitle>Heart Rhythm</addtitle><description>Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. Methods A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. Results Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL ( P <.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2 ) and presented an increased efficacy in models with a depressed INa ( P <.01). Conclusion Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.</description><subject>Action Potentials - physiology</subject><subject>Anti-Arrhythmia Agents - pharmacology</subject><subject>Atrial fibrillation</subject><subject>Atrial Fibrillation - diagnosis</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrial Fibrillation - metabolism</subject><subject>Atrial Fibrillation - physiopathology</subject><subject>Atrial Remodeling</subject><subject>Calcium Channels - metabolism</subject><subject>Calcium current</subject><subject>Cardiovascular</subject><subject>Computer Simulation</subject><subject>Humans</subject><subject>Ionic currents</subject><subject>Mathematical modeling</subject><subject>Models, Cardiovascular</subject><subject>Rotor dynamics</subject><subject>Sodium Channels - metabolism</subject><issn>1547-5271</issn><issn>1556-3871</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUtGK1TAQDaK46-oXCJIfaHeStEmv4MK6uCos-KA-hzRJ96am6ZKkV_oN_rTpXl3UF8lDzjBzzjBzBqGXBGoChJ-P9T7m_VTTEtTQ1UC7R-iUtC2vWCfI4w03omqpICfoWUojAN1xYE_RCRUt3zUNO0U_3iqvgra4t_m7tQGn2bhlwioYrJXXG9ZLjDbkhJdgbPSrC7dY7-McnMYqR6c8HlwfnfcquzngbOPkwj1-jS8DdkXVeafngkouLf1odcYHVah9SeQVp7yY9Tl6Miif7Itf_xn6ev3uy9WH6ubT-49XlzeVbkmTKwN2MEa0IICDAt10A6NiMKrhijZDeZZw0RvRD3TogBcWMRYMF53aNcywM3Rx1L1b-skaXWaLysu76CYVVzkrJ__OBLeXt_NBtpQSwaAIsKOAjnNK0Q4PXAJy80aO8t4buXkjoZPFm8J69WfbB85vM0rBm2OBLcMfnI0yaWeLOcbFsjBpZvefBhf_8LV3xSTlv9nVpnFeYih7lUQmKkF-3s5juw7CGXBBGPsJn6e8Og</recordid><startdate>20161201</startdate><enddate>20161201</enddate><creator>Liberos, Alejandro, PhD</creator><creator>Bueno-Orovio, Alfonso, PhD</creator><creator>Rodrigo, Miguel, MS</creator><creator>Ravens, Ursula, MD</creator><creator>Hernandez-Romero, Ismael, MS</creator><creator>Fernandez-Aviles, Francisco, MD, PhD</creator><creator>Guillem, Maria S., PhD</creator><creator>Rodriguez, Blanca, PhD</creator><creator>Climent, Andreu M., PhD</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>5PM</scope></search><sort><creationdate>20161201</creationdate><title>Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study</title><author>Liberos, Alejandro, PhD ; Bueno-Orovio, Alfonso, PhD ; Rodrigo, Miguel, MS ; Ravens, Ursula, MD ; Hernandez-Romero, Ismael, MS ; Fernandez-Aviles, Francisco, MD, PhD ; Guillem, Maria S., PhD ; Rodriguez, Blanca, PhD ; Climent, Andreu M., PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-d0efdd7507060a0c48f327fda46a24f4f4e167bd7bf2f806c511de0d678a943d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Action Potentials - physiology</topic><topic>Anti-Arrhythmia Agents - pharmacology</topic><topic>Atrial fibrillation</topic><topic>Atrial Fibrillation - diagnosis</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrial Fibrillation - metabolism</topic><topic>Atrial Fibrillation - physiopathology</topic><topic>Atrial Remodeling</topic><topic>Calcium Channels - metabolism</topic><topic>Calcium current</topic><topic>Cardiovascular</topic><topic>Computer Simulation</topic><topic>Humans</topic><topic>Ionic currents</topic><topic>Mathematical modeling</topic><topic>Models, Cardiovascular</topic><topic>Rotor dynamics</topic><topic>Sodium Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liberos, Alejandro, PhD</creatorcontrib><creatorcontrib>Bueno-Orovio, Alfonso, PhD</creatorcontrib><creatorcontrib>Rodrigo, Miguel, MS</creatorcontrib><creatorcontrib>Ravens, Ursula, MD</creatorcontrib><creatorcontrib>Hernandez-Romero, Ismael, MS</creatorcontrib><creatorcontrib>Fernandez-Aviles, Francisco, MD, PhD</creatorcontrib><creatorcontrib>Guillem, Maria S., PhD</creatorcontrib><creatorcontrib>Rodriguez, Blanca, PhD</creatorcontrib><creatorcontrib>Climent, Andreu M., PhD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Heart rhythm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liberos, Alejandro, PhD</au><au>Bueno-Orovio, Alfonso, PhD</au><au>Rodrigo, Miguel, MS</au><au>Ravens, Ursula, MD</au><au>Hernandez-Romero, Ismael, MS</au><au>Fernandez-Aviles, Francisco, MD, PhD</au><au>Guillem, Maria S., PhD</au><au>Rodriguez, Blanca, PhD</au><au>Climent, Andreu M., PhD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study</atitle><jtitle>Heart rhythm</jtitle><addtitle>Heart Rhythm</addtitle><date>2016-12-01</date><risdate>2016</risdate><volume>13</volume><issue>12</issue><spage>2358</spage><epage>2365</epage><pages>2358-2365</pages><issn>1547-5271</issn><eissn>1556-3871</eissn><abstract>Background Atrial remodeling as a result of long-standing persistent atrial fibrillation (AF) induces substrate modifications that lead to different perpetuation mechanisms than in paroxysmal AF and a reduction in the efficacy of antiarrhythmic treatments. Objective The purpose of this study was to identify the ionic current modifications that could destabilize reentries during chronic AF and serve to personalize antiarrhythmic strategies. Methods A population of 173 mathematical models of remodeled human atrial tissue with realistic intersubject variability was developed based on action potential recordings of 149 patients diagnosed with AF. The relationship of each ionic current with AF maintenance and the dynamics of functional reentries (rotor meandering, dominant frequency) were evaluated by means of 3-dimensional simulations. Results Self-sustained reentries were maintained in 126 (73%) of the simulations. AF perpetuation was associated with higher expressions of INa and ICaL ( P <.01), with no significant differences in the remaining currents. ICaL blockade promoted AF extinction in 30% of these 126 models. The mechanism of AF termination was related with collisions between rotors because of an increase in rotor meandering (1.71 ± 2.01cm2 ) and presented an increased efficacy in models with a depressed INa ( P <.01). Conclusion Mathematical simulations based on a population of models representing intersubject variability allow the identification of ionic mechanisms underlying rotor dynamics and the definition of new personalized pharmacologic strategies. Our results suggest that the underlying mechanism of the diverging success of ICaL block as an antiarrhythmic strategy is dependent on the basal availability of sodium and calcium ion channel conductivities.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27569443</pmid><doi>10.1016/j.hrthm.2016.08.028</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1547-5271 |
| ispartof | Heart rhythm, 2016-12, Vol.13 (12), p.2358-2365 |
| issn | 1547-5271 1556-3871 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5221730 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Action Potentials - physiology Anti-Arrhythmia Agents - pharmacology Atrial fibrillation Atrial Fibrillation - diagnosis Atrial Fibrillation - drug therapy Atrial Fibrillation - metabolism Atrial Fibrillation - physiopathology Atrial Remodeling Calcium Channels - metabolism Calcium current Cardiovascular Computer Simulation Humans Ionic currents Mathematical modeling Models, Cardiovascular Rotor dynamics Sodium Channels - metabolism |
| title | Balance between sodium and calcium currents underlying chronic atrial fibrillation termination: An in silico intersubject variability study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T03%3A02%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Balance%20between%20sodium%20and%20calcium%20currents%20underlying%20chronic%20atrial%20fibrillation%20termination:%20An%20in%20silico%20intersubject%20variability%20study&rft.jtitle=Heart%20rhythm&rft.au=Liberos,%20Alejandro,%20PhD&rft.date=2016-12-01&rft.volume=13&rft.issue=12&rft.spage=2358&rft.epage=2365&rft.pages=2358-2365&rft.issn=1547-5271&rft.eissn=1556-3871&rft_id=info:doi/10.1016/j.hrthm.2016.08.028&rft_dat=%3Celsevier_pubme%3E1_s2_0_S1547527116306713%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/27569443&rft_els_id=1_s2_0_S1547527116306713&rfr_iscdi=true |