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
2018
Kir2.1 & Nav1.5 in Sickness and in Health
Strauss B, Akar FG. Kir2.1 & Nav1.5 in Sickness and in Health. Circulation Research 2018, 122: 1482-1484. PMID: 29798894, PMCID: PMC6181135, DOI: 10.1161/circresaha.118.313029.Commentaries, Editorials and Letters
2016
Starve a fever to heal a heart? Interleukin-18 gives new meaning to an old adage
Akar FG. Starve a fever to heal a heart? Interleukin-18 gives new meaning to an old adage. AJP Heart And Circulatory Physiology 2016, 311: h311-h312. PMID: 27342879, DOI: 10.1152/ajpheart.00445.2016.Commentaries, Editorials and Letters
2013
Glutathione 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
2007
Mitochondrial Ion Channels in Cardiac Function and Dysfunction
O'Rourke B, Cortassa S, Akar F, Aon M. Mitochondrial Ion Channels in Cardiac Function and Dysfunction. Novartis Foundation Symposia 2007, 287: 140-156. PMID: 18074636, PMCID: PMC2692520, DOI: 10.1002/9780470725207.ch10.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMitochondrial ion channelsIon channelsReactive oxygen species (ROS) signalsNumerous signaling pathwaysBurst of ROSMitochondrial networkMitochondrial physiologyPlasma membraneSpecies signalSignaling pathwaysCellular activitiesCellular targetsMitochondrial functionEnergy transductionMitochondriaVast modificationsPhysiological conditionsOrgan levelDisease developmentPotential therapeutic interventionsWidespread effectsImportant targetSurprising insightsKey roleCenter of organizations
2005
The mitochondrial origin of postischemic arrhythmias
Akar FG, Aon MA, Tomaselli GF, O'Rourke B. The mitochondrial origin of postischemic arrhythmias. Journal Of Clinical Investigation 2005, 115: 3527-3535. PMID: 16284648, PMCID: PMC1280968, DOI: 10.1172/jci25371.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAnionsArrhythmias, CardiacDose-Response Relationship, DrugElectrophysiologyGuinea PigsHeartIntracellular MembranesIon ChannelsIschemiaMembrane PotentialsMicroscopy, ConfocalMitochondria, HeartMyocardial IschemiaMyocardial ReperfusionMyocardial Reperfusion InjuryMyocardiumMyocytes, CardiacOscillometryReactive Oxygen SpeciesReceptors, GABA-AReperfusion InjuryTemperatureTime FactorsConceptsAction potentialsVentricular fibrillationPostischemic functional recoveryIschemic heart diseaseGuinea pig heartsNew therapeutic targetsAbnormal electrical activationPostischemic arrhythmiasReperfusion arrhythmiasFunctional recoveryGlobal ischemiaHeart diseaseBolus infusionArrhythmia preventionElectrophysiological changesAP shorteningControl heartsPostischemic heartsBenzodiazepine receptorsElectrophysiological substrateTherapeutic targetArrhythmiasReperfusionPig heartsMitochondrial benzodiazepine receptorMolecular Basis of Arrhythmias
Shah M, Akar FG, Tomaselli GF. Molecular Basis of Arrhythmias. Circulation 2005, 112: 2517-2529. PMID: 16230503, DOI: 10.1161/circulationaha.104.494476.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIon channel subunit genesChannel subunit genesSubunit geneMolecular basisBasic biologySingle gene disordersNew molecular targetsCardiac arrhythmiasCellular basisGene disordersMolecular targetsMolecular pathogenesisPathophysiological conditionsCritical roleCatecholaminergic polymorphic ventricular tachycardiaPrimary electrical diseasePathological remodelingFundamental mechanismsPolymorphic ventricular tachycardiaImportant insightsLong QT syndromeElectrical diseaseVentricular tachycardiaBrugada syndromeGenesAbnormal 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
Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes
Xue T, Cho HC, Akar FG, Tsang SY, Jones SP, Marbán E, Tomaselli GF, Li RA. Functional Integration of Electrically Active Cardiac Derivatives From Genetically Engineered Human Embryonic Stem Cells With Quiescent Recipient Ventricular Cardiomyocytes. Circulation 2004, 111: 11-20. PMID: 15611367, DOI: 10.1161/01.cir.0000151313.18547.a2.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAdrenergic beta-AgonistsAnimalsCell DifferentiationCell FusionCells, CulturedDefective VirusesElectrophysiologyFemaleGenes, ReporterGenetic VectorsGiant CellsGreen Fluorescent ProteinsGuinea PigsHeartHeart Conduction SystemHeart VentriclesHIV-1HumansIsoproterenolLidocaineMiceMyocardial ContractionMyocytes, CardiacOrgan Culture TechniquesPericardiumPluripotent Stem CellsPyrimidinesRatsTransduction, GeneticConceptsVentricular cardiomyocytesCardiac impulse generationBeta-adrenergic agonist isoproterenolGuinea pig heartsSite of injectionStem cellsHuman embryonic stem cellsCell-based therapiesContractile activityAgonist isoproterenolPharmacological agentsVentricular myocardiumLeft ventricleEx vivoDonor cardiomyocytesPig heartsHuman cardiomyocytesRecombinant lentivirusMembrane depolarizationCardiomyocytesFunctional syncytiumImpulse generationEmbryonic stem cellsMyocardiumEpicardial surface
2003
Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure
Akar FG, Rosenbaum DS. Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure. Circulation Research 2003, 93: 638-645. PMID: 12933704, DOI: 10.1161/01.res.0000092248.59479.ae.Peer-Reviewed Original ResearchConceptsPolymorphic ventricular tachycardiaHeart failureQT interval prolongationQT intervalM cellsConduction blockAPD prolongationTransmural wallAction potential duration prolongationRapid ventricular pacingTransmural heterogeneityFunctional conduction blockVentricular tachyarrhythmiasPremature impulsesSubepicardial zoneVentricular pacingVentricular tachycardiaHF phenotypesDuration prolongationCanine wedge preparationSelective prolongationDecremental conductionAction potentialsOptical action potentialsVentricular wall
2001
Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation
Akar F, Roth B, Rosenbaum D. Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation. AJP Heart And Circulatory Physiology 2001, 281: h533-h542. PMID: 11454554, DOI: 10.1152/ajpheart.2001.281.2.h533.Peer-Reviewed Original Research
2000
Cellular basis for dispersion of repolarization underlying reentrant arrhythmias
Akar F, Laurita K, Rosenbaum D. Cellular basis for dispersion of repolarization underlying reentrant arrhythmias. Journal Of Electrocardiology 2000, 33: 23-31. PMID: 11265727, DOI: 10.1054/jelc.2000.20313.Peer-Reviewed Original Research