Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern
Abstract Aims Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintena...
Gespeichert in:
| Veröffentlicht in: | Cardiovascular research 2021-03, Vol.117 (4), p.1078-1090 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1090 |
|---|---|
| container_issue | 4 |
| container_start_page | 1078 |
| container_title | Cardiovascular research |
| container_volume | 117 |
| creator | Handa, Balvinder S Li, Xinyang Baxan, Nicoleta Roney, Caroline H Shchendrygina, Anastasia Mansfield, Catherine A Jabbour, Richard J Pitcher, David S Chowdhury, Rasheda A Peters, Nicholas S Ng, Fu Siong |
| description | Abstract
Aims
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.
Methods and results
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P |
| doi_str_mv | 10.1093/cvr/cvaa141 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7983010</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/cvr/cvaa141</oup_id><sourcerecordid>2403029496</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-81387cf69481336fb451f2aa87e00a2138ddbca73659ec447f4aeabab9e4765c3</originalsourceid><addsrcrecordid>eNp9kUFP3DAQhS3Uit0CJ-6VTwipSmvHjp1ckCpESyWkXgpXa-I4wavETu0EaXvmh-MlC7SXHizbep_feOYhdErJZ0oq9kU_hLQAKKcHaE1lUWQs58U7tCaElJlggq3Qhxg36VoUkh-iVdJJToRco8c746Zg9dxDwK2tg-17mKx3eDD6HpyNAwbX4K73NfRvhA9b7EOXgD8LDsHgxkwmDNaZBtdb3MGIN7PTz7L289hb1z2b7Vx8tBGPMKUX7hi9b6GP5mS_H6Hbb1e_Lq-zm5_ff1x-vck0l-WUlZSVUrei4unERFvzgrY5QCkNIZAntWlqDZKJojKac9lyMFBDXRkuRaHZEbpYfMe5Hkyjd61Dr8ZgBwhb5cGqfxVn71XnH5SsSkYoSQbne4Pgf88mTmqwUZs0EGf8HFUaKyN5xSuR0E8LqlOrMZj2tQwlapebSrmpfW6J_vj3z17Zl6AScLYAaY7_dXoCGZinLg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2403029496</pqid></control><display><type>article</type><title>Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Handa, Balvinder S ; Li, Xinyang ; Baxan, Nicoleta ; Roney, Caroline H ; Shchendrygina, Anastasia ; Mansfield, Catherine A ; Jabbour, Richard J ; Pitcher, David S ; Chowdhury, Rasheda A ; Peters, Nicholas S ; Ng, Fu Siong</creator><creatorcontrib>Handa, Balvinder S ; Li, Xinyang ; Baxan, Nicoleta ; Roney, Caroline H ; Shchendrygina, Anastasia ; Mansfield, Catherine A ; Jabbour, Richard J ; Pitcher, David S ; Chowdhury, Rasheda A ; Peters, Nicholas S ; Ng, Fu Siong</creatorcontrib><description><![CDATA[Abstract
Aims
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.
Methods and results
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.
Conclusion
The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.
Graphical Abstract]]></description><identifier>ISSN: 0008-6363</identifier><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvaa141</identifier><identifier>PMID: 32402067</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Action Potentials ; Animals ; Disease Models, Animal ; Electrocardiography ; Fibrosis ; Gap Junctions - pathology ; Heart Rate ; Heart Ventricles - pathology ; Heart Ventricles - physiopathology ; Isolated Heart Preparation ; Models, Cardiovascular ; Original ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Ventricular Fibrillation - pathology ; Ventricular Fibrillation - physiopathology ; Voltage-Sensitive Dye Imaging</subject><ispartof>Cardiovascular research, 2021-03, Vol.117 (4), p.1078-1090</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-81387cf69481336fb451f2aa87e00a2138ddbca73659ec447f4aeabab9e4765c3</citedby><cites>FETCH-LOGICAL-c478t-81387cf69481336fb451f2aa87e00a2138ddbca73659ec447f4aeabab9e4765c3</cites><orcidid>0000-0002-8681-4368 ; 0000-0003-4204-1014 ; 0000-0001-6539-6542 ; 0000-0001-6809-0928 ; 0000-0002-7028-2942</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32402067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Handa, Balvinder S</creatorcontrib><creatorcontrib>Li, Xinyang</creatorcontrib><creatorcontrib>Baxan, Nicoleta</creatorcontrib><creatorcontrib>Roney, Caroline H</creatorcontrib><creatorcontrib>Shchendrygina, Anastasia</creatorcontrib><creatorcontrib>Mansfield, Catherine A</creatorcontrib><creatorcontrib>Jabbour, Richard J</creatorcontrib><creatorcontrib>Pitcher, David S</creatorcontrib><creatorcontrib>Chowdhury, Rasheda A</creatorcontrib><creatorcontrib>Peters, Nicholas S</creatorcontrib><creatorcontrib>Ng, Fu Siong</creatorcontrib><title>Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description><![CDATA[Abstract
Aims
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.
Methods and results
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.
Conclusion
The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.
Graphical Abstract]]></description><subject>Action Potentials</subject><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Electrocardiography</subject><subject>Fibrosis</subject><subject>Gap Junctions - pathology</subject><subject>Heart Rate</subject><subject>Heart Ventricles - pathology</subject><subject>Heart Ventricles - physiopathology</subject><subject>Isolated Heart Preparation</subject><subject>Models, Cardiovascular</subject><subject>Original</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Time Factors</subject><subject>Ventricular Fibrillation - pathology</subject><subject>Ventricular Fibrillation - physiopathology</subject><subject>Voltage-Sensitive Dye Imaging</subject><issn>0008-6363</issn><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUFP3DAQhS3Uit0CJ-6VTwipSmvHjp1ckCpESyWkXgpXa-I4wavETu0EaXvmh-MlC7SXHizbep_feOYhdErJZ0oq9kU_hLQAKKcHaE1lUWQs58U7tCaElJlggq3Qhxg36VoUkh-iVdJJToRco8c746Zg9dxDwK2tg-17mKx3eDD6HpyNAwbX4K73NfRvhA9b7EOXgD8LDsHgxkwmDNaZBtdb3MGIN7PTz7L289hb1z2b7Vx8tBGPMKUX7hi9b6GP5mS_H6Hbb1e_Lq-zm5_ff1x-vck0l-WUlZSVUrei4unERFvzgrY5QCkNIZAntWlqDZKJojKac9lyMFBDXRkuRaHZEbpYfMe5Hkyjd61Dr8ZgBwhb5cGqfxVn71XnH5SsSkYoSQbne4Pgf88mTmqwUZs0EGf8HFUaKyN5xSuR0E8LqlOrMZj2tQwlapebSrmpfW6J_vj3z17Zl6AScLYAaY7_dXoCGZinLg</recordid><startdate>20210321</startdate><enddate>20210321</enddate><creator>Handa, Balvinder S</creator><creator>Li, Xinyang</creator><creator>Baxan, Nicoleta</creator><creator>Roney, Caroline H</creator><creator>Shchendrygina, Anastasia</creator><creator>Mansfield, Catherine A</creator><creator>Jabbour, Richard J</creator><creator>Pitcher, David S</creator><creator>Chowdhury, Rasheda A</creator><creator>Peters, Nicholas S</creator><creator>Ng, Fu Siong</creator><general>Oxford University Press</general><scope>TOX</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8681-4368</orcidid><orcidid>https://orcid.org/0000-0003-4204-1014</orcidid><orcidid>https://orcid.org/0000-0001-6539-6542</orcidid><orcidid>https://orcid.org/0000-0001-6809-0928</orcidid><orcidid>https://orcid.org/0000-0002-7028-2942</orcidid></search><sort><creationdate>20210321</creationdate><title>Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern</title><author>Handa, Balvinder S ; Li, Xinyang ; Baxan, Nicoleta ; Roney, Caroline H ; Shchendrygina, Anastasia ; Mansfield, Catherine A ; Jabbour, Richard J ; Pitcher, David S ; Chowdhury, Rasheda A ; Peters, Nicholas S ; Ng, Fu Siong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-81387cf69481336fb451f2aa87e00a2138ddbca73659ec447f4aeabab9e4765c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Action Potentials</topic><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>Electrocardiography</topic><topic>Fibrosis</topic><topic>Gap Junctions - pathology</topic><topic>Heart Rate</topic><topic>Heart Ventricles - pathology</topic><topic>Heart Ventricles - physiopathology</topic><topic>Isolated Heart Preparation</topic><topic>Models, Cardiovascular</topic><topic>Original</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Time Factors</topic><topic>Ventricular Fibrillation - pathology</topic><topic>Ventricular Fibrillation - physiopathology</topic><topic>Voltage-Sensitive Dye Imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Handa, Balvinder S</creatorcontrib><creatorcontrib>Li, Xinyang</creatorcontrib><creatorcontrib>Baxan, Nicoleta</creatorcontrib><creatorcontrib>Roney, Caroline H</creatorcontrib><creatorcontrib>Shchendrygina, Anastasia</creatorcontrib><creatorcontrib>Mansfield, Catherine A</creatorcontrib><creatorcontrib>Jabbour, Richard J</creatorcontrib><creatorcontrib>Pitcher, David S</creatorcontrib><creatorcontrib>Chowdhury, Rasheda A</creatorcontrib><creatorcontrib>Peters, Nicholas S</creatorcontrib><creatorcontrib>Ng, Fu Siong</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Handa, Balvinder S</au><au>Li, Xinyang</au><au>Baxan, Nicoleta</au><au>Roney, Caroline H</au><au>Shchendrygina, Anastasia</au><au>Mansfield, Catherine A</au><au>Jabbour, Richard J</au><au>Pitcher, David S</au><au>Chowdhury, Rasheda A</au><au>Peters, Nicholas S</au><au>Ng, Fu Siong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2021-03-21</date><risdate>2021</risdate><volume>117</volume><issue>4</issue><spage>1078</spage><epage>1090</epage><pages>1078-1090</pages><issn>0008-6363</issn><eissn>1755-3245</eissn><abstract><![CDATA[Abstract
Aims
Conflicting data exist supporting differing mechanisms for sustaining ventricular fibrillation (VF), ranging from disorganized multiple-wavelet activation to organized rotational activities (RAs). Abnormal gap junction (GJ) coupling and fibrosis are important in initiation and maintenance of VF. We investigated whether differing ventricular fibrosis patterns and the degree of GJ coupling affected the underlying VF mechanism.
Methods and results
Optical mapping of 65 Langendorff-perfused rat hearts was performed to study VF mechanisms in control hearts with acute GJ modulation, and separately in three differing chronic ventricular fibrosis models; compact fibrosis (CF), diffuse fibrosis (DiF), and patchy fibrosis (PF). VF dynamics were quantified with phase mapping and frequency dominance index (FDI) analysis, a power ratio of the highest amplitude dominant frequency in the cardiac frequency spectrum. Enhanced GJ coupling with rotigaptide (n = 10) progressively organized fibrillation in a concentration-dependent manner; increasing FDI (0 nM: 0.53 ± 0.04, 80 nM: 0.78 ± 0.03, P < 0.001), increasing RA-sustained VF time (0 nM: 44 ± 6%, 80 nM: 94 ± 2%, P < 0.001), and stabilized RAs (maximum rotations for an RA; 0 nM: 5.4 ± 0.5, 80 nM: 48.2 ± 12.3, P < 0.001). GJ uncoupling with carbenoxolone progressively disorganized VF; the FDI decreased (0 µM: 0.60 ± 0.05, 50 µM: 0.17 ± 0.03, P < 0.001) and RA-sustained VF time decreased (0 µM: 61 ± 9%, 50 µM: 3 ± 2%, P < 0.001). In CF, VF activity was disorganized and the RA-sustained VF time was the lowest (CF: 27 ± 7% vs. PF: 75 ± 5%, P < 0.001). Global fibrillatory organization measured by FDI was highest in PF (PF: 0.67 ± 0.05 vs. CF: 0.33 ± 0.03, P < 0.001). PF harboured the longest duration and most spatially stable RAs (patchy: 1411 ± 266 ms vs. compact: 354 ± 38 ms, P < 0.001). DiF (n = 11) exhibited an intermediately organized VF pattern, sustained by a combination of multiple-wavelets and short-lived RAs.
Conclusion
The degree of GJ coupling and pattern of fibrosis influences the mechanism sustaining VF. There is a continuous spectrum of organization in VF, ranging between globally organized fibrillation sustained by stable RAs and disorganized, possibly multiple-wavelet driven fibrillation with no RAs.
Graphical Abstract]]></abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>32402067</pmid><doi>10.1093/cvr/cvaa141</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8681-4368</orcidid><orcidid>https://orcid.org/0000-0003-4204-1014</orcidid><orcidid>https://orcid.org/0000-0001-6539-6542</orcidid><orcidid>https://orcid.org/0000-0001-6809-0928</orcidid><orcidid>https://orcid.org/0000-0002-7028-2942</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0008-6363 |
| ispartof | Cardiovascular research, 2021-03, Vol.117 (4), p.1078-1090 |
| issn | 0008-6363 1755-3245 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7983010 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Action Potentials Animals Disease Models, Animal Electrocardiography Fibrosis Gap Junctions - pathology Heart Rate Heart Ventricles - pathology Heart Ventricles - physiopathology Isolated Heart Preparation Models, Cardiovascular Original Rats Rats, Sprague-Dawley Time Factors Ventricular Fibrillation - pathology Ventricular Fibrillation - physiopathology Voltage-Sensitive Dye Imaging |
| title | Ventricular fibrillation mechanism and global fibrillatory organization are determined by gap junction coupling and fibrosis pattern |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T19%3A28%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ventricular%20fibrillation%20mechanism%20and%20global%20fibrillatory%20organization%20are%20determined%20by%20gap%20junction%20coupling%20and%20fibrosis%20pattern&rft.jtitle=Cardiovascular%20research&rft.au=Handa,%20Balvinder%20S&rft.date=2021-03-21&rft.volume=117&rft.issue=4&rft.spage=1078&rft.epage=1090&rft.pages=1078-1090&rft.issn=0008-6363&rft.eissn=1755-3245&rft_id=info:doi/10.1093/cvr/cvaa141&rft_dat=%3Cproquest_pubme%3E2403029496%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2403029496&rft_id=info:pmid/32402067&rft_oup_id=10.1093/cvr/cvaa141&rfr_iscdi=true |