Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch
PurposeMyocardial stretch is a proarrhythmic factor. Eleclazine (GS6615) is a late sodium current (INaL) inhibitor that has shown protective effects against arrhythmias in various experimental models. Data on its effects during myocardial stretch are lacking. The aim of this study was to investigate...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2025.1525836/full |
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| author | Francisco J. Chorro Francisco J. Chorro Francisco J. Chorro Luis Such-Miquel Luis Such-Miquel Samuel Cuñat Oscar Arias-Mutis Oscar Arias-Mutis Patricia Genovés Patricia Genovés Manuel Zarzoso Manuel Zarzoso Antonio Alberola Antonio Alberola Luis Such-Belenguer Luis Such-Belenguer Irene Del Canto Irene Del Canto |
| author_facet | Francisco J. Chorro Francisco J. Chorro Francisco J. Chorro Luis Such-Miquel Luis Such-Miquel Samuel Cuñat Oscar Arias-Mutis Oscar Arias-Mutis Patricia Genovés Patricia Genovés Manuel Zarzoso Manuel Zarzoso Antonio Alberola Antonio Alberola Luis Such-Belenguer Luis Such-Belenguer Irene Del Canto Irene Del Canto |
| author_sort | Francisco J. Chorro |
| collection | DOAJ |
| description | PurposeMyocardial stretch is a proarrhythmic factor. Eleclazine (GS6615) is a late sodium current (INaL) inhibitor that has shown protective effects against arrhythmias in various experimental models. Data on its effects during myocardial stretch are lacking. The aim of this study was to investigate the electrophysiological modifications induced by eleclazine basally and during acute ventricular stretch.MethodsLeft ventricular stretch was induced at baseline and during perfusion with eleclazine in 26 Langendorff rabbit heart preparations. Programmed stimulation and high-resolution mapping techniques were applied using multiple epicardial electrodes.ResultsAt baseline, both the ventricular refractory period measured at a fixed cycle length (250 m) and its surrogate obtained during ventricular fibrillation (VF) decreased significantly during stretch (baseline 128 ± 15 vs. stretch 110 ± 14 m; n = 15; p < 0.001, and baseline 52 ± 13 vs. stretch 44 ± 9 m; n = 11; p < 0.05), while the VF dominant frequency (DF) increased significantly (DF baseline 13 ± 3 vs. stretch 17 ± 5Hz; n = 11; p < 0.01). Eleclazine 1.4 μM prolonged refractoriness, diminished both DF and conduction velocity during the arrhythmia, and avoided the stretch induced variations in refractoriness (baseline 148 ± 19 vs. stretch 150 ± 23 m; n = 15; ns, and baseline 73 ± 15 vs. stretch 77 ± 15 m; n = 11; ns) and in DF (baseline 12 ± 5 vs. stretch 12 ± 3 Hz; ns). The VF complexity index was inversely related to refractoriness (r = −0.64; p < 0.001). Under eleclazine perfusion, the VF activation patterns were less complex, and the arrhythmia stopped in 6 out of 11 experiments (55%; p < 0.05 vs. baseline).ConclusionEleclazine (GS6615) reduced the proarrhythmic electrophysiological changes induced by myocardial stretch and slowed and simplified activation patterns during VF in the experimental model used. |
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| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-a90b117a73bb445bafa21e76d2e8b8a32025-01-31T06:39:50ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2025-01-011610.3389/fphys.2025.15258361525836Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretchFrancisco J. Chorro0Francisco J. Chorro1Francisco J. Chorro2Luis Such-Miquel3Luis Such-Miquel4Samuel Cuñat5Oscar Arias-Mutis6Oscar Arias-Mutis7Patricia Genovés8Patricia Genovés9Manuel Zarzoso10Manuel Zarzoso11Antonio Alberola12Antonio Alberola13Luis Such-Belenguer14Luis Such-Belenguer15Irene Del Canto16Irene Del Canto17Department of Medicine, University of Valencia, Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainResearch Institute, Valencia Clinic Hospital (INCLIVA), Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainDepartment of Physiotherapy, University of Valencia, Valencia, SpainDepartment of Physiology, University of Valencia, Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainResearch Institute, Valencia Clinic Hospital (INCLIVA), Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainResearch Institute, Valencia Clinic Hospital (INCLIVA), Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainDepartment of Physiotherapy, University of Valencia, Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainDepartment of Physiology, University of Valencia, Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainDepartment of Physiology, University of Valencia, Valencia, SpainBiomedical Research Center Network - Cardiovascular Diseases (CIBERCV), Carlos III Health Institute, Madrid, SpainDepartment of Electronic Engineering, University of Valencia, Burjassot, SpainPurposeMyocardial stretch is a proarrhythmic factor. Eleclazine (GS6615) is a late sodium current (INaL) inhibitor that has shown protective effects against arrhythmias in various experimental models. Data on its effects during myocardial stretch are lacking. The aim of this study was to investigate the electrophysiological modifications induced by eleclazine basally and during acute ventricular stretch.MethodsLeft ventricular stretch was induced at baseline and during perfusion with eleclazine in 26 Langendorff rabbit heart preparations. Programmed stimulation and high-resolution mapping techniques were applied using multiple epicardial electrodes.ResultsAt baseline, both the ventricular refractory period measured at a fixed cycle length (250 m) and its surrogate obtained during ventricular fibrillation (VF) decreased significantly during stretch (baseline 128 ± 15 vs. stretch 110 ± 14 m; n = 15; p < 0.001, and baseline 52 ± 13 vs. stretch 44 ± 9 m; n = 11; p < 0.05), while the VF dominant frequency (DF) increased significantly (DF baseline 13 ± 3 vs. stretch 17 ± 5Hz; n = 11; p < 0.01). Eleclazine 1.4 μM prolonged refractoriness, diminished both DF and conduction velocity during the arrhythmia, and avoided the stretch induced variations in refractoriness (baseline 148 ± 19 vs. stretch 150 ± 23 m; n = 15; ns, and baseline 73 ± 15 vs. stretch 77 ± 15 m; n = 11; ns) and in DF (baseline 12 ± 5 vs. stretch 12 ± 3 Hz; ns). The VF complexity index was inversely related to refractoriness (r = −0.64; p < 0.001). Under eleclazine perfusion, the VF activation patterns were less complex, and the arrhythmia stopped in 6 out of 11 experiments (55%; p < 0.05 vs. baseline).ConclusionEleclazine (GS6615) reduced the proarrhythmic electrophysiological changes induced by myocardial stretch and slowed and simplified activation patterns during VF in the experimental model used.https://www.frontiersin.org/articles/10.3389/fphys.2025.1525836/fullarrhythmiasmyocardial stretchEleclazine (GS6615)ventricular fibrillationcardiac mapping |
| spellingShingle | Francisco J. Chorro Francisco J. Chorro Francisco J. Chorro Luis Such-Miquel Luis Such-Miquel Samuel Cuñat Oscar Arias-Mutis Oscar Arias-Mutis Patricia Genovés Patricia Genovés Manuel Zarzoso Manuel Zarzoso Antonio Alberola Antonio Alberola Luis Such-Belenguer Luis Such-Belenguer Irene Del Canto Irene Del Canto Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch Frontiers in Physiology arrhythmias myocardial stretch Eleclazine (GS6615) ventricular fibrillation cardiac mapping |
| title | Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| title_full | Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| title_fullStr | Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| title_full_unstemmed | Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| title_short | Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| title_sort | effects of eleclazine gs6615 on the proarrhythmic electrophysiological changes induced by myocardial stretch |
| topic | arrhythmias myocardial stretch Eleclazine (GS6615) ventricular fibrillation cardiac mapping |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2025.1525836/full |
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