2021
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation
Raad N, Bittihn P, Cacheux M, Jeong D, Ilkan Z, Ceholski D, Kohlbrenner E, Zhang L, Cai CL, Kranias EG, Hajjar RJ, Stillitano F, Akar FG. Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation. Circulation 2021, 144: 441-454. PMID: 34024116, PMCID: PMC8456417, DOI: 10.1161/circulationaha.119.043502.Peer-Reviewed Original ResearchConceptsHuman PLNRapid pacingInterventricular activation delayHumanized mouse modelAction potential prolongationLocal conduction blockSteep repolarization gradientsArrhythmogenic featuresMacroreentrant circuitHemodynamic changesElectric remodelingElectrophysiological remodelingRight ventricleVentricular tachycardiaPotential prolongationSudden deathConduction blockMouse modelAdult knockArrhythmia susceptibilityAdrenergic stimulationStructural remodelingArrhythmogenic phenotypeArrhythmia mechanismsRegulatory protein phospholamban
2019
Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans
Cacheux M, Strauss B, Raad N, Ilkan Z, Hu J, Benard L, Feske S, Hulot JS, Akar FG. Cardiomyocyte-Specific STIM1 (Stromal Interaction Molecule 1) Depletion in the Adult Heart Promotes the Development of Arrhythmogenic Discordant Alternans. Circulation Arrhythmia And Electrophysiology 2019, 12: e007382-e007382. PMID: 31726860, PMCID: PMC6867678, DOI: 10.1161/circep.119.007382.Peer-Reviewed Original ResearchConceptsVT/VFAPD alternansStore-operated CaVentricular tachycardia/ventricular fibrillationOptical action potential mappingAdult heartVT/Adult murine modelDiscordant alternansConduction velocity slowingSarcoplasmic reticulum CaArrhythmogenic discordant alternansInitial beatsEarly mortalityFlox/Poor survivalVentricular fibrillationDiscordant APD alternansMurine modelCardiac hypertrophyConduction velocityLittermate controlsAdult miceRapid pacingElectrophysiological substrate