2022
Humanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes
Stevens TL, Manring HR, Wallace MJ, Argall A, Dew T, Papaioannou P, Antwi-Boasiako S, Xu X, Campbell SG, Akar FG, Borzok MA, Hund TJ, Mohler PJ, Koenig SN, El Refaey M. Humanized Dsp ACM Mouse Model Displays Stress-Induced Cardiac Electrical and Structural Phenotypes. Cells 2022, 11: 3049. PMID: 36231013, PMCID: PMC9562631, DOI: 10.3390/cells11193049.Peer-Reviewed Original ResearchConceptsArrhythmogenic cardiomyopathyMouse modelStructural phenotypesFibro-fatty infiltrationFirst mouse modelHeart failureChamber dilationVentricular arrhythmiasPressure overloadArrhythmic eventsCardiac performanceCardiac stressSudden deathCardiovascular stressInherited disorderG variantConnexin 43MiceDesmosomal genesReduced expressionExternal stressorsACM familyDisease developmentMurine equivalentIncomplete penetrance
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
2013
Electrophysiological Remodeling in Heart Failure
Akar F, Tomaselli G. Electrophysiological Remodeling in Heart Failure. 2013, 369-386. DOI: 10.1007/978-1-4471-4881-4_22.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHeart failureTreatment of arrhythmiasCellular electrophysiological propertiesIon channelsSafe therapyConduction abnormalitiesElectrophysiological remodelingSudden deathNovel pharmacologicalArrhythmogenic triggersElectrophysiological propertiesAction potentialsArrhythmiasFunctional consequencesIonic mechanismsMolecular mechanismsOrgan levelFailureTherapyAbnormalitiesPharmacologicalRepolarizationGlutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs
Xie C, Biary N, Tocchetti CG, Aon MA, Paolocci N, Kauffman J, Akar FG. Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs. AJP Heart And Circulatory Physiology 2013, 304: h916-h926. PMID: 23376824, PMCID: PMC3625895, DOI: 10.1152/ajpheart.00026.2012.Peer-Reviewed Original ResearchConceptsSham-operated heartsChronic hyperglycemiaOxidative stressAPD heterogeneityGuinea pigsOptical action potential mappingType 1 diabetes mellitusVT/VFGuinea pig modelAction potential durationDaily insulinDiabetes mellitusArrhythmia suppressionProarrhythmic propertiesGlycemic levelsVentricular tachycardiaSaline injectionVentricular fibrillationSudden deathGlucose levelsStreptozotocinArrhythmic triggersNormal heartsTreatment groupsPotential duration
2005
Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences
Akar FG, Tomaselli GF. Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences. Trends In Cardiovascular Medicine 2005, 15: 259-264. PMID: 16226681, DOI: 10.1016/j.tcm.2005.08.002.Peer-Reviewed Original ResearchConceptsConduction abnormalitiesVentricular dysfunctionHeart failureMolecular mechanismsLeft ventricular dysfunctionNonischemic heart failureIschemic heart diseaseExtracellular matrixGenesis of arrhythmiasMyocyte excitabilityMechanistic differencesOrgan levelMembrane excitabilityVentricular tachyarrhythmiasDisease etiologyMyocardial infarctionHeart diseaseArrhythmogenic substrateSudden deathArrhythmic consequencesCell couplingAbnormalitiesBasic mechanismsDysfunctionExcitability