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
2021
Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias
Haghighi K, Gardner G, Vafiadaki E, Kumar M, Green LC, Ma J, Crocker JS, Koch S, Arvanitis DA, Bidwell P, Rubinstein J, van de Leur R, Doevendans PA, Akar FG, Tranter M, Wang HS, Sadayappan S, DeMazumder D, Sanoudou D, Hajjar RJ, Stillitano F, Kranias EG. Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias. Journal Of Personalized Medicine 2021, 11: 502. PMID: 34204946, PMCID: PMC8226909, DOI: 10.3390/jpm11060502.Peer-Reviewed Original ResearchRight ventricleMalignant ventricular arrhythmiasEarly risk factorsAction potential durationCaMKII inhibitor KN93Stress-induced impairmentCellular pathogenic mechanismsProarrhythmic parametersSR Ca loadPrognostic factorsRisk stratificationVentricular arrhythmiasHumanized micePoor prognosisVentricular tachyarrhythmiasFatal arrhythmiasAsymptomatic carriersElectrocardiographic featuresRisk factorsAtrioventricular conductionContractile parametersPotential durationCardiomyopathy onsetPathogenic mechanismsHuman wild type
2009
Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy
Aiba T, Hesketh GG, Barth AS, Liu T, Daya S, Chakir K, Dimaano VL, Abraham TP, O'Rourke B, Akar FG, Kass DA, Tomaselli GF. Electrophysiological Consequences of Dyssynchronous Heart Failure and Its Restoration by Resynchronization Therapy. Circulation 2009, 119: 1220-1230. PMID: 19237662, PMCID: PMC2703676, DOI: 10.1161/circulationaha.108.794834.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsBundle-Branch BlockCalciumCalcium ChannelsCoronary CirculationDogsEchocardiographyElectrocardiographyHeart FailureHomeostasisKv Channel-Interacting ProteinsMaleMyocytes, CardiacPacemaker, ArtificialPatch-Clamp TechniquesPotassium Channels, Inwardly RectifyingRNA, MessengerSarcoplasmic Reticulum Calcium-Transporting ATPasesShal Potassium ChannelsConceptsCardiac resynchronization therapyAction potential durationRight atrial pacingCalcium transient amplitudeHeart failurePotential durationResynchronization therapyAtrial pacingElectrophysiological consequencesLeft bundle-branch ablationTransient amplitudeSarcoplasmic reticulumWhole-cell patch clampDyssynchronous heart failureProtein levelsIon channel remodelingSame pacing rateLeft ventricular anteriorQuantitative polymerase chain reactionSurvival benefitBiventricular pacingVentricular arrhythmiasDyssynchronous contractionPolymerase chain reactionElectrophysiological changes
2008
A ligand to the mitochondrial benzodiazepine receptor prevents ventricular arrhythmias and LV dysfunction after ischemia or glutathione depletion
Brown D, Aon M, Akar F, O’Rourke B. A ligand to the mitochondrial benzodiazepine receptor prevents ventricular arrhythmias and LV dysfunction after ischemia or glutathione depletion. The FASEB Journal 2008, 22: 747.7-747.7. DOI: 10.1096/fasebj.22.1_supplement.747.7.Peer-Reviewed Original ResearchContractile dysfunctionBenzodiazepine receptorsGlobal ischemia/reperfusionOxidative stressMitochondrial benzodiazepine receptorIschemia/reperfusionGuinea pig heartsSignificant clinical implicationsAnti-oxidant defensesReduced arrhythmiasLV dysfunctionVentricular dysfunctionR injuryVentricular arrhythmiasInduced arrhythmiasNormoxic perfusionIsolated myocytesDysfunctionClinical implicationsArrhythmiasIntact heartMetabolic challengesPig heartsGlutathione depletionMitochondrial membrane potential
2007
Regulation of ion channels and arrhythmias in the ischemic heart
Akar JG, Akar FG. Regulation of ion channels and arrhythmias in the ischemic heart. Journal Of Electrocardiology 2007, 40: s37-s41. PMID: 17993326, DOI: 10.1016/j.jelectrocard.2007.05.020.Peer-Reviewed Original ResearchConceptsIschemic injuryElectrophysiological changesIschemic heart diseaseBest treatment strategyCoronary eventsReperfusion phaseVentricular arrhythmiasIschemic episodesHeart diseaseLeading causeElectrical dysfunctionTreatment strategiesIschemic heartMetabolic substratesPatientsArrhythmiasKey cellularTime courseInjuryIon channelsHeartDysfunctionMortalityDisease
2006
Mapping arrhythmias in the failing heart: from Langendorff to patient
Akar JG, Akar FG. Mapping arrhythmias in the failing heart: from Langendorff to patient. Journal Of Electrocardiology 2006, 39: s19-s23. PMID: 16920143, DOI: 10.1016/j.jelectrocard.2006.03.011.Peer-Reviewed Educational MaterialsConceptsHeart failureVentricular arrhythmiasOptical action potential mappingSudden cardiac deathCardiac deathIntact tissue preparationsCardiac remodelingMost arrhythmiasArrhythmic substrateArrhythmiasElectrophysiological propertiesMapping arrhythmiasTissue levelsIndividual myocytesMajor causeReentrant excitationOrgan system levelPatientsMultiple mechanismsTissue preparationsHeartRecent findingsHost of changesCellular studiesLangendorff
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