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
Primary 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 substrateOptical Action Potential Mapping in Acute Models of Ischemia–Reperfusion Injury: Probing the Arrhythmogenic Role of the Mitochondrial Translocator Protein
Ilkan Z, Strauss B, Campana C, Akar FG. Optical Action Potential Mapping in Acute Models of Ischemia–Reperfusion Injury: Probing the Arrhythmogenic Role of the Mitochondrial Translocator Protein. Methods In Molecular Biology 2018, 1816: 133-143. PMID: 29987816, DOI: 10.1007/978-1-4939-8597-5_10.Peer-Reviewed Original ResearchConceptsOptical action potential mappingIschemia-reperfusion injuryTranslocator proteinPost-ischemic arrhythmiasIonotropic propertiesPostischemic arrhythmiasR injuryHypertensive ratsAcute modelArrhythmogenic roleElectrophysiological substrateElectrophysiological propertiesArrhythmia mechanismsPharmacological inhibitionIntact heartInjuryTSPO ligandsMitochondrial translocator proteinArrhythmiasTSPO geneHeartPatientsRatsQuantitative assessmentIncidence
2017
Increased Afterload Following Myocardial Infarction Promotes Conduction-Dependent Arrhythmias That Are Unmasked by Hypokalemia
Motloch LJ, Ishikawa K, Xie C, Hu J, Aguero J, Fish KM, Hajjar RJ, Akar FG. Increased Afterload Following Myocardial Infarction Promotes Conduction-Dependent Arrhythmias That Are Unmasked by Hypokalemia. JACC Basic To Translational Science 2017, 2: 258-269. PMID: 28798965, PMCID: PMC5547890, DOI: 10.1016/j.jacbts.2017.02.002.Peer-Reviewed Original ResearchAdvanced ischemic heart diseasePost-myocardial infarction patientsIschemic heart diseaseSudden cardiac deathNew large animal modelLarge animal modelMechanisms of arrhythmiasIncreased afterloadResistant hypertensionCardiac deathWorsen outcomesAnterior MIInfarction patientsHeart diseasePathophysiological significanceAnimal modelsElectrophysiological substrateAfterloadHypokalemiaDisease phenotypePatientsArrhythmiasRelevant modelHypertensionMI
2010
Left ventricular repolarization heterogeneity as an arrhythmic substrate in heart failure.
Akar FG. Left ventricular repolarization heterogeneity as an arrhythmic substrate in heart failure. Minerva Cardioangiologica 2010, 58: 205-12. PMID: 20440250.ChaptersConceptsHeart failureElectrophysiological substrateSudden cardiac deathCalcium handling proteinsRepolarization gradientsVentricular repolarization heterogeneityHeterogeneous remodelingCardiac deathCardiac functionArrhythmic substrateLeft ventriculeHandling proteinsMuscle layerPathophysiological remodelingRepolarization heterogeneityTissue levelsOrgan system levelArrhythmiasGap junctionsIon channelsOverview of mechanismsSub-cellular changesRemodelingFailureVentricule
2008
Arrhythmia Mechanisms in the Failing Heart
JIN H, LYON AR, AKAR FG. Arrhythmia Mechanisms in the Failing Heart. Pacing And Clinical Electrophysiology 2008, 31: 1048-1056. PMID: 18684263, DOI: 10.1111/j.1540-8159.2008.01134.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHeart failureArrhythmia mechanismsFundamental arrhythmia mechanismsSudden cardiac deathLethal ventricular tachyarrhythmiasCalcium handling proteinsEffective treatment strategiesCardiac deathMalignant arrhythmiasVentricular tachyarrhythmiasElectrical remodelingConduction abnormalitiesFailing HeartTreatment strategiesLethal arrhythmiasElectrophysiological substrateHandling proteinsAction potentialsPatientsArrhythmiasIon channelsDeathHeartTachyarrhythmiasAbnormalities
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
2002
The Electrophysiological Substrate for Reentry: Unique Insights from High-Resolution Optical Mapping with Voltage-Sensitive Dyes
Rosenbaum D, Akar F. The Electrophysiological Substrate for Reentry: Unique Insights from High-Resolution Optical Mapping with Voltage-Sensitive Dyes. 2002, 568-595. DOI: 10.1201/b14064-18.Peer-Reviewed Original ResearchMajor public health problemReentrant arrhythmiasSudden cardiac deathPublic health problemNormal cardiac rhythmHemodynamic deteriorationCardiac deathVentricular arrhythmiasConduction disturbancesLethal arrhythmiasVoltage-sensitive dyeCardiac rhythmElectrophysiological substrateReentrant circuitMaintenance of reentryArrhythmiasElectrical defibrillationHealth problemsArrhythmia mechanismsMyocardial excitabilityFocal arrhythmiasIntact heartCardiac impulseResolution optical mappingReentrant excitation