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
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 electrophysiologyGlutathione 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
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
2005
Abnormal 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