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
2009
Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy
Jin H, Chemaly ER, Lee A, Kho C, Hadri L, Hajjar RJ, Akar FG. Mechanoelectrical remodeling and arrhythmias during progression of hypertrophy. The FASEB Journal 2009, 24: 451-463. PMID: 19825979, PMCID: PMC2812033, DOI: 10.1096/fj.09-136622.Peer-Reviewed Original ResearchConceptsConduction delayLeft ventricular mechanical dysfunctionEnd-stage heart failureTissue levelsVentricular mechanical dysfunctionIncidence of arrhythmiasSudden cardiac deathZO-1Pressure overload hypertrophyAction potential prolongationProgression of hypertrophyDisease developmentLV dysfunctionCardiac deathDephosphorylation of Cx43Heart failureAortic bandingElectrical remodelingVentricular tachycardiaMechanical dysfunctionOverload hypertrophyElectrophysiological changesRat modelPotential prolongationProtein ZO-1