2018
Optical 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
2015
The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease
Motloch LJ, Hu J, Akar FG. The Mitochondrial Translocator Protein and Arrhythmogenesis in Ischemic Heart Disease. Oxidative Medicine And Cellular Longevity 2015, 2015: 234104. PMID: 25918579, PMCID: PMC4397036, DOI: 10.1155/2015/234104.Peer-Reviewed Original ResearchConceptsIschemic heart diseaseHeart diseaseTranslocator proteinAcute ischemia-reperfusion injuryReactive oxygen speciesIschemia-reperfusion injuryMultiple organ systemsExcitation-contraction couplingMultiple cardiovascular disordersPermeability transition poreRole of TSPOMyocardial infarctionInflammatory processDiverse pathophysiological processesImmune responseCardiovascular disordersTherapeutic targetPathophysiological processesOrgan systemsDiagnostic markerMitochondrial dysfunctionDiseaseAbundant expressionMitochondrial translocator proteinROS release
2014
Eacpt-0032 TAT-HKII Induced Reduction in Mitochondrial Bound Hexokinase II Increases Ischemia Reperfusion Injury by Increased Respiration and Increased Ros Levels
Nederlof R, Gürel E, Xie C, Eerbeek O, Koeman A, Hollmann M, Southworth R, Akar F, Mik E, Zuurbier C. Eacpt-0032 TAT-HKII Induced Reduction in Mitochondrial Bound Hexokinase II Increases Ischemia Reperfusion Injury by Increased Respiration and Increased Ros Levels. Clinical Therapeutics 2014, 36: e13. DOI: 10.1016/j.clinthera.2014.05.051.Peer-Reviewed Original Research
2013
TAT-HKII induced reduction in mitochondrial bound hexokinase II increases ischemia reperfusion injury by increased respiration and increased ROS levels
Nederlof R, Guerel E, Xie C, Eerbeek O, Koeman A, Hollmann M, Southworth R, Akar F, Mik E, Zuurbier C. TAT-HKII induced reduction in mitochondrial bound hexokinase II increases ischemia reperfusion injury by increased respiration and increased ROS levels. European Heart Journal 2013, 34: 3694. DOI: 10.1093/eurheartj/eht309.3694.Peer-Reviewed Original ResearchMitochondrial oxygen tensionPeptide treatmentReperfusion injuryCardiac functionLDH activityROS productionControl groupHexokinase IIIschemia/reperfusion injuryOxygen consumptionIschemia-reperfusion injuryReactive oxygen speciesOxygen tensionCardiac oxygen consumptionCell deathBorderline ischemiaReperfusion necrosisR damageMin reperfusionReversible ischemiaIrreversible ischemiaMin ischemiaIschemiaTreatment groupsReperfusionMitochondrial 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
Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis
Smeele KM, Southworth R, Wu R, Xie C, Nederlof R, Warley A, Nelson JK, van Horssen P, van den Wijngaard JP, Heikkinen S, Laakso M, Koeman A, Siebes M, Eerbeek O, Akar FG, Ardehali H, Hollmann MW, Zuurbier CJ. Disruption of Hexokinase II–Mitochondrial Binding Blocks Ischemic Preconditioning and Causes Rapid Cardiac Necrosis. Circulation Research 2011, 108: 1165-1169. PMID: 21527739, DOI: 10.1161/circresaha.111.244962.Peer-Reviewed Original ResearchConceptsIschemic preconditioningWild-type heartsCardiac functionProtective effectHKII levelsBaseline cardiac functionIschemia-reperfusion injuryNormal cardiac functionMitochondrial permeability transition openingContractile impairmentReperfusion injuryAcute reductionCardiac necrosisMyocardial functionGlycolytic enzymes hexokinaseCardiac contractionMild mitochondrial uncouplingMembrane depolarizationMitochondrial membrane depolarizationHKIIMitochondrial hexokinaseControl peptideHeartPreconditioningTissue disruptionDeciphering Arrhythmia Mechanisms: Tools of the Trade
Salama G, Akar FG. Deciphering Arrhythmia Mechanisms: Tools of the Trade. Cardiac Electrophysiology Clinics 2011, 3: 11-21. PMID: 21572551, PMCID: PMC3093299, DOI: 10.1016/j.ccep.2010.10.013.Peer-Reviewed Original ResearchArrhythmia mechanismsIschemia-reperfusion injuryCalcium handling propertiesLong QT syndromeMultiple cardiovascular disordersHeart failureCardiac functionCardiovascular disordersQT syndromeComplex arrhythmiasAction potentialsOptical action potentialsPathophysiological remodelingTissue levelsOrgan system levelRepolarization gradientsArrhythmiasSub-cellular changesSyndromeInjuryLevels