2013
Mitochondrial targets for arrhythmia suppression: is there a role for pharmacological intervention?
Akar FG. Mitochondrial targets for arrhythmia suppression: is there a role for pharmacological intervention? Journal Of Interventional Cardiac Electrophysiology 2013, 37: 249-258. PMID: 23824789, DOI: 10.1007/s10840-013-9809-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMitochondrial targetsMitochondrial dysfunctionCritical cellular functionsCell death pathwaysCellular redox statusIon channel functionMitochondrial networkCellular functionsDeath pathwaysMitochondrial originIschemia-reperfusion injuryCommon cardiovascular disordersMitochondrial bioenergeticsExcitation-contraction couplingChannel functionRedox statusMechanistic linkHeart failureArrhythmia suppressionPharmacological interventionsCardiovascular disordersCentral mechanismsDysfunctionArrhythmogenesisEnergy productionPathophysiological Consequences of TAT-HKII Peptide Administration Are Independent of Impaired Vascular Function and Ensuing Ischemia
Nederlof R, Xie C, Eerbeek O, Koeman A, Milstein DM, Hollmann MW, Mik EG, Warley A, Southworth R, Akar FG, Zuurbier CJ. Pathophysiological Consequences of TAT-HKII Peptide Administration Are Independent of Impaired Vascular Function and Ensuing Ischemia. Circulation Research 2013, 112: e8-e13. PMID: 23329797, PMCID: PMC3596767, DOI: 10.1161/circresaha.112.274308.Peer-Reviewed Original ResearchConceptsVascular functionIschemic preconditioningMyocardial dysfunctionCardiac functionPeptide administrationHexokinase IIOptical action potential mappingAcute myocardial dysfunctionImpaired vascular functionIschemia-reperfusion injuryDeleterious effectsIschemic injuryCardioprotective effectsProtective effectIschemiaPathophysiological consequencesIntact myocardiumDehydrogenase releaseIntact heartAdministrationLactate productionDysfunctionRole of mitochondriaInjuryCritical regulator
2011
Alterations in Mitochondrial State 4→3 Transition Underlie Stress-Induced Energetic-Redox Imbalance and Myocyte Dysfunction in Diabetic Mice
Tocchetti C, Stanley B, Shi S, Watson W, Cortassa S, Akar F, Paolocci N, Aon M. Alterations in Mitochondrial State 4→3 Transition Underlie Stress-Induced Energetic-Redox Imbalance and Myocyte Dysfunction in Diabetic Mice. Biophysical Journal 2011, 100: 292a. DOI: 10.1016/j.bpj.2010.12.1795.Peer-Reviewed Original Research
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 potentialElectrophysiological remodeling in Dilated Cardiomyopathy and Heart Failure
Akar F, Tomaselli G. Electrophysiological remodeling in Dilated Cardiomyopathy and Heart Failure. 2008, 290-304. DOI: 10.1007/978-1-84628-854-8_19.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsHeart failureCardiac remodelingComplete heart blockStructural heart diseaseAtrial fibrillationHeart blockMyocardial infarctionVentricular pacingElectrophysiological remodelingHeart diseaseMechanical dysfunctionHeart ratePersistent changesRemodelingActivation sequenceEntire organKey regulatory proteinsGene expressionExtracellular matrixInfarctionTachycardiaCardiomyopathyFailureDysfunctionFibrillation
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 channelsHeartDysfunctionMortalityDiseaseDynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure
Akar FG, Nass RD, Hahn S, Cingolani E, Shah M, Hesketh GG, DiSilvestre D, Tunin RS, Kass DA, Tomaselli GF. Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. AJP Heart And Circulatory Physiology 2007, 293: h1223-h1230. PMID: 17434978, DOI: 10.1152/ajpheart.00079.2007.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsCardiac Pacing, ArtificialConnexin 43Disease Models, AnimalDogsDown-RegulationGap JunctionsHeart Conduction SystemHeart FailureMalePhosphorylationProtein IsoformsTachycardia, VentricularTime FactorsVentricular Function, LeftVentricular PressureVentricular RemodelingConceptsEnd-stage heart failureHeart failureConduction velocityMechanical dysfunctionCV slowingPacing-induced heart failureDevelopment of HFOnset of HFMechanical functionCx43 isoformConduction abnormalitiesCx43 lateralizationAdvanced stageBaseline levelsMyocardial preparationsPhosphorylation of Cx43High-resolution optical mappingSustained downregulationMarked increaseDephosphorylated Cx43LVEDPGap junction propertiesConduction changesDysfunctionTime course
2005
Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences
Akar FG, Tomaselli GF. Conduction Abnormalities in Nonischemic Dilated Cardiomyopathy: Basic Mechanisms and Arrhythmic Consequences. Trends In Cardiovascular Medicine 2005, 15: 259-264. PMID: 16226681, DOI: 10.1016/j.tcm.2005.08.002.Peer-Reviewed Original ResearchConceptsConduction abnormalitiesVentricular dysfunctionHeart failureMolecular mechanismsLeft ventricular dysfunctionNonischemic heart failureIschemic heart diseaseExtracellular matrixGenesis of arrhythmiasMyocyte excitabilityMechanistic differencesOrgan levelMembrane excitabilityVentricular tachyarrhythmiasDisease etiologyMyocardial infarctionHeart diseaseArrhythmogenic substrateSudden deathArrhythmic consequencesCell couplingAbnormalitiesBasic mechanismsDysfunctionExcitabilityIon channels as novel therapeutic targets in heart failure
Akar FG, Tomaselli GF. Ion channels as novel therapeutic targets in heart failure. Annals Of Medicine 2005, 37: 44-54. PMID: 15902846, DOI: 10.1080/07853890510007214.Peer-Reviewed Original ResearchConceptsHeart failureIon channel functionAnti-arrhythmic therapyLethal ventricular tachyarrhythmiasCalcium handling proteinsNovel therapeutic targetPublic health epidemicIon channel dysfunctionChannel functionVentricular tachyarrhythmiasTherapeutic targetChannel dysfunctionHandling proteinsSodium currentHealth epidemicNovel targetImpulse generationElectrical phenotypeIon channelsCurrent understandingTachyarrhythmiasFailureDysfunctionTherapyAbnormalities