2013
Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium
Turnbull IC, Karakikes I, Serrao GW, Backeris P, Lee J, Xie C, Senyei G, Gordon RE, Li RA, Akar FG, Hajjar RJ, Hulot J, Costa KD. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. The FASEB Journal 2013, 28: 644-654. PMID: 24174427, PMCID: PMC3898643, DOI: 10.1096/fj.13-228007.Peer-Reviewed Original ResearchConceptsHuman myocardiumPreclinical modelsCardiac tissueAlternative preclinical modelsAction potential durationFrank-Starling mechanismCycle length dependenceHuman embryonic stem cell-derived cardiomyocytesDose-response curveEmbryonic stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHuman heart musclePositive chronotropicInotropic responseCardiac refractorinessCell-derived cardiomyocytesTrabecular musclesPotential durationPharmacodynamic modelMRNA expressionMyocardiumHeart muscleCardiac-specific genesTranslational researchCardiac electrophysiology
2006
Bioartificial Sinus Node Constructed via In Vivo Gene Transfer of an Engineered Pacemaker HCN Channel Reduces the Dependence on Electronic Pacemaker in a Sick-Sinus Syndrome Model
Tse HF, Xue T, Lau CP, Siu CW, Wang K, Zhang QY, Tomaselli GF, Akar FG, Li RA. Bioartificial Sinus Node Constructed via In Vivo Gene Transfer of an Engineered Pacemaker HCN Channel Reduces the Dependence on Electronic Pacemaker in a Sick-Sinus Syndrome Model. Circulation 2006, 114: 1000-1011. PMID: 16923751, DOI: 10.1161/circulationaha.106.615385.Peer-Reviewed Original ResearchAnimalsArrhythmias, CardiacBioartificial OrgansCyclic Nucleotide-Gated Cation ChannelsDisease Models, AnimalElectrophysiologyGene Transfer TechniquesGuinea PigsHeart RateHyperpolarization-Activated Cyclic Nucleotide-Gated ChannelsIon ChannelsMicePacemaker, ArtificialPotassium ChannelsSick Sinus SyndromeSinoatrial NodeSwineSwine, Miniature
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 receptor
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 surfaceHeterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall
Poelzing S, Akar FG, Baron E, Rosenbaum DS. Heterogeneous connexin43 expression produces electrophysiological heterogeneities across ventricular wall. AJP Heart And Circulatory Physiology 2004, 286: h2001-h2009. PMID: 14704225, DOI: 10.1152/ajpheart.00987.2003.Peer-Reviewed Original Research
2003
Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito
Akar FG, Wu RC, Deschenes I, Armoundas AA, Piacentino V, Houser SR, Tomaselli GF. Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito. AJP Heart And Circulatory Physiology 2003, 286: h602-h609. PMID: 14527940, DOI: 10.1152/ajpheart.00673.2003.Peer-Reviewed Original ResearchConceptsTransient outwardPhenotypic differencesKv channel-interacting proteinsIndependent transient outwardChannel-interacting proteinsProtein chemical techniquesSteady-state inactivationCanine ventricular myocytesWestern blot analysisElectrical remodelingChannel subunit genesMonoexponential time coursePharmacological sensitivityVentricular repolarizationCardiac diseaseElectrophysiological roleCanine ventricularHuman cardiac diseasePosttranslational modificationsVentricular myocytesSubunit genePharmacological propertiesDiseased heartPhenotypic propertiesOxidative stressTransmural 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 ResearchMeSH KeywordsAction PotentialsAnimalsArrhythmias, CardiacDogsElectrophysiologyHeartHeart FailureIn Vitro TechniquesMaleConceptsPolymorphic 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
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