title: Ventricular tachycardia from the healed myocardial infarction scar: validation of an animal model and utility of gene therapy.
abstract: Life-threatening ventricular arrhythmias generally occur in the setting of structural heart disease. Current clinical options for patients at risk for these rhythm disturbances are limited. We developed a porcine model of inducible ventricular tachycardia originating in the border region of a healed myocardial infarction scar. After validating the model, we assessed gene transfer techniques, focusing on local modification of border zone tissues. We found that gene transfer of the dominant negative KCNH2-G628S mutation to the anteroseptal infarct border caused localized prolongation of effective refractory period in the target region and eliminated all ventricular arrhythmia inducibility. In this work, we characterize the animal model and review the gene transfer results.
authors.affiliation: Heart and Vascular Research Center, Case Western Reserve University School of Medicine, Cleveland, OH 44109, USA.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sasano
authors.forename: Kamilla
authors.initials: K
authors.lastname: Kelemen
authors.forename: Ian D
authors.initials: ID
authors.lastname: Greener
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Donahue
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology; D013552:Swine; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000628:therapy*