2023
Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy
Ng R, Gokhan I, Stankey P, Akar F, Campbell S. Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy. AJP Heart And Circulatory Physiology 2023, 325: h1373-h1385. PMID: 37830983, PMCID: PMC10977872, DOI: 10.1152/ajpheart.00709.2022.Peer-Reviewed Original ResearchArrhythmogenic cardiomyopathyDiastolic stretchConduction deficitsConduction velocityIntensity of exerciseAction potential parametersDifferent time pointsDisease progressionHigh afterloadContractile functionHemodynamic parametersProgressive disorderUnderlying pathomechanismsArrhythmia vulnerabilityConduction defectsPhysiological shorteningHeart tissueConnexin 43Time pointsERK signalingCardiomyopathyLysosome activityCardiac cycleDesmosomal proteinsExercise
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
2018
Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension
Strauss B, Sassi Y, Bueno-Beti C, Ilkan Z, Raad N, Cacheux M, Bisserier M, Turnbull IC, Kohlbrenner E, Hajjar RJ, Hadri L, Akar FG. Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension. Journal Of Molecular And Cellular Cardiology 2018, 127: 20-30. PMID: 30502350, PMCID: PMC6561115, DOI: 10.1016/j.yjmcc.2018.11.017.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAerosolsAnimalsArrhythmias, CardiacConnexin 43Disease Models, AnimalGene Transfer TechniquesGenetic TherapyHeart Conduction SystemHumansMalePotassium ChannelsPulmonary Arterial HypertensionRats, Sprague-DawleyRNA, MessengerSarcoplasmic Reticulum Calcium-Transporting ATPasesTracheaConceptsPulmonary arterial hypertensionSudden cardiac deathVentricular tachyarrhythmiasCTRL heartsExpression of Cx43Conduction velocityArterial hypertensionHeart rateAP durationAdvanced pulmonary arterial hypertensionIncidence of VTOptical action potential mappingPacing-induced ventricular tachyarrhythmiasRisk of VTAEP substrateElectro-mechanical dysfunctionImpaired chronotropic responseMinimal conduction velocitiesRight ventricular failureSustained ventricular tachyarrhythmiasAPD heterogeneityPulmonary vascular remodelingRapid heart rateAge-matched ratsIntra-tracheal deliveryPrimary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction
Motloch LJ, Cacheux M, Ishikawa K, Xie C, Hu J, Aguero J, Fish KM, Hajjar RJ, Akar FG. Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction. Journal Of The American Heart Association 2018, 7: e009598. PMID: 30371209, PMCID: PMC6222964, DOI: 10.1161/jaha.118.009598.Peer-Reviewed Original ResearchConceptsMyocardial infarctionVentricular tachycardiaSERCA 2aVirus serotype 1Heart failureOptical action potential mappingPacing-induced ventricular tachycardiaIschemic heart failureNonischemic heart failureSerotype 1SERCA2a gene transferChronic myocardial infarctionExpression of Cx43Contractile reserveVelocity reserveHemodynamic functionDobutamine stressAnterior MIElectrophysiological effectsQRS durationConduction reserveConduction velocityNaive pigsAnimal modelsElectrophysiological substrate
2007
Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure
Akar FG, Nass RD, Hahn S, Cingolani E, Shah M, Hesketh GG, DiSilvestre D, Tunin RS, Kass DA, Tomaselli GF. Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. AJP Heart And Circulatory Physiology 2007, 293: h1223-h1230. PMID: 17434978, DOI: 10.1152/ajpheart.00079.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCardiac Pacing, ArtificialConnexin 43Disease Models, AnimalDogsDown-RegulationGap JunctionsHeart Conduction SystemHeart FailureMalePhosphorylationProtein IsoformsTachycardia, VentricularTime FactorsVentricular Function, LeftVentricular PressureVentricular RemodelingConceptsEnd-stage heart failureHeart failureConduction velocityMechanical dysfunctionCV slowingPacing-induced heart failureDevelopment of HFOnset of HFMechanical functionCx43 isoformConduction abnormalitiesCx43 lateralizationAdvanced stageBaseline levelsMyocardial preparationsPhosphorylation of Cx43High-resolution optical mappingSustained downregulationMarked increaseDephosphorylated Cx43LVEDPGap junction propertiesConduction changesDysfunctionTime course
2005
Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts
Spragg DD, Akar FG, Helm RH, Tunin RS, Tomaselli GF, Kass DA. Abnormal conduction and repolarization in late-activated myocardium of dyssynchronously contracting hearts. Cardiovascular Research 2005, 67: 77-86. PMID: 15885674, DOI: 10.1016/j.cardiores.2005.03.008.Peer-Reviewed Original ResearchConceptsAction potential durationConduction velocityRefractory periodElectrophysiological remodelingArrhythmia susceptibilityIntraventricular conduction delayLeft ventricular dyssynchronyGap junction protein expressionJunction protein expressionCalcium cycling proteinsTotal expressionDyssynchronous heartsLV dysfunctionMechanical dyssynchronyUntreated dogsVentricular dyssynchronyCardiac dyssynchronyControl dogsLateral LVRadiofrequency ablationAnterior wallConduction delayDyssynchronyMyocardial segmentsPotential duration
2004
Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy
Akar FG, Spragg DD, Tunin RS, Kass DA, Tomaselli GF. Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy. Circulation Research 2004, 95: 717-725. PMID: 15345654, DOI: 10.1161/01.res.0000144125.61927.1c.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArrhythmias, CardiacBlotting, WesternCadherinsCardiac Pacing, ArtificialCardiomyopathy, DilatedCell SizeConnexin 43DogsFibrosisGap JunctionsHeart Conduction SystemMicroscopy, ConfocalMicroscopy, FluorescenceMyocardiumMyocytes, CardiacNeural ConductionPatch-Clamp TechniquesPhosphorylationProtein Processing, Post-TranslationalSubcellular Fractions