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
2010
Use‐Dependent Modulation of Myocardial Conduction by a New Class of HERG Agonists: Deal Breaker or Cherry on Top?
AKAR FG. Use‐Dependent Modulation of Myocardial Conduction by a New Class of HERG Agonists: Deal Breaker or Cherry on Top? Journal Of Cardiovascular Electrophysiology 2010, 21: 930-932. PMID: 20367661, DOI: 10.1111/j.1540-8167.2010.01747.x.Commentaries, Editorials and Letters
2009
Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes†
Aiba T, Hesketh GG, Liu T, Carlisle R, Villa-Abrille MC, O'Rourke B, Akar FG, Tomaselli GF. Na+ channel regulation by Ca2+/calmodulin and Ca2+/calmodulin-dependent protein kinase II in guinea-pig ventricular myocytes†. Cardiovascular Research 2009, 85: 454-463. PMID: 19797425, PMCID: PMC2802203, DOI: 10.1093/cvr/cvp324.Peer-Reviewed Original ResearchConceptsAutocamtide-2-related inhibitory peptideDependent protein kinase IIProtein kinase IIKinase IIChannel gatingGlutathione S-transferase fusion peptidesCAMP-dependent proteinIQ-like motifSpecific CaMKII inhibitorC-terminusChannel regulationPresence of CaMInactivation phenotypeCaMKIICaMKII inhibitorFusion peptideInactivationSlow inactivationFraction of channelsDistinct effectsInhibitorsPeptidesInhibitory peptidesGatingCalmodulin
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 surface
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
1999
Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation
Pastore J, Girouard S, Laurita K, Akar F, Rosenbaum D. Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation. Circulation 1999, 99: 1385-1394. PMID: 10077525, DOI: 10.1161/01.cir.99.10.1385.Peer-Reviewed Original Research
1998
Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart
Laurita K, Girouard S, Akar F, Rosenbaum D. Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart. Circulation 1998, 98: 2774-2780. PMID: 9851966, DOI: 10.1161/01.cir.98.24.2774.Peer-Reviewed Original ResearchConceptsVentricular fibrillation thresholdSingle premature stimulusPremature stimuliArrhythmia vulnerabilityBaseline levelsPremature stimulationS1S2 intervalRepolarization gradientsGuinea pig heartsBaseline pacingFibrillation thresholdArrhythmogenic substrateVentricular fibrillationVentricular sitesStimulus-induced changesVentricular repolarizationCoupling intervalCardiac arrhythmiasS2 beatElectrophysiological propertiesAction potentialsOptical action potentialsHeterogeneous electrophysiological propertiesPig heartsRepolarization