Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension
Strauss B, Sassi Y, Bueno-Beti C, Ilkan Z, Raad N, Cacheux M, Bisserier M, Turnbull IC, Kohlbrenner E, Hajjar RJ, Hadri L, Akar FG. Intra-tracheal gene delivery of aerosolized SERCA2a to the lung suppresses ventricular arrhythmias in a model of pulmonary arterial hypertension. Journal Of Molecular And Cellular Cardiology 2018, 127: 20-30. PMID: 30502350, PMCID: PMC6561115, DOI: 10.1016/j.yjmcc.2018.11.017.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAerosolsAnimalsArrhythmias, CardiacConnexin 43Disease Models, AnimalGene Transfer TechniquesGenetic TherapyHeart Conduction SystemHumansMalePotassium ChannelsPulmonary Arterial HypertensionRats, Sprague-DawleyRNA, MessengerSarcoplasmic Reticulum Calcium-Transporting ATPasesTracheaConceptsPulmonary arterial hypertensionSudden cardiac deathVentricular tachyarrhythmiasCTRL heartsExpression of Cx43Conduction velocityArterial hypertensionHeart rateAP durationAdvanced pulmonary arterial hypertensionIncidence of VTOptical action potential mappingPacing-induced ventricular tachyarrhythmiasRisk of VTAEP substrateElectro-mechanical dysfunctionImpaired chronotropic responseMinimal conduction velocitiesRight ventricular failureSustained ventricular tachyarrhythmiasAPD heterogeneityPulmonary vascular remodelingRapid heart rateAge-matched ratsIntra-tracheal deliveryPrimary 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 substrate