J Donahue

..Gene transfer continues to be a promising technology, but patience is required as these problems are solved and the therapies make their way through the preclinical and clinical testing process...

..In this review, we present a model of postinfarct ventricular tachycardia, a method for gene delivery to this area, and results of KCNH2-G628S gene transfer to manipulate cellular refractory properties in the arrhythmia model...

..In this review, I discuss the basic mechanisms of ventricular arrhythmias and summarize the literature on the use of gene therapy for ventricular tachyarrhythmias...

..Fibrosis, cellular dysfunction, and gap junction protein alterations occur in AF and cause conduction delay. We performed this study to test the hypothesis that gap junction protein overexpression would improve conduction and prevent AF...

..In this work, we characterize the animal model and review the gene transfer results...

..No proarrhythmia or other negative effects were discernable. Our results demonstrate the potential viability of gene therapy for ablation of ventricular arrhythmias...

..This method was well tolerated by the animals. We demonstrate targeted, homogeneous, high efficiency gene transfer using a method that should be transferable for eventual human usage...

..Safety and efficacy limit currently available atrial fibrillation (AF) therapies. We hypothesized that atrial gene transfer would allow focal manipulation of atrial electrophysiology and, by eliminating reentry, would prevent AF...

..Arrhythmia gene therapy is a field in its infancy, and future human applications are dependent on solutions to the problems discussed in this review...

..A variety of animal models exist, including models of lone atrial fibrillation and models of atrial fibrillation in the setting of heart failure, aging, or pericardial inflammation. This article reviews these various models...

..This review will discuss novel biological strategies that are currently under development and may eventually have impact on the management of atrial fibrillation...

..This model can be used for further investigation into the pathophysiology and treatment of atrial fibrillation and advanced heart failure...

..However, in the acquired LQTs1 and 2 beneficial effects of fastpac diminished and in a combination thereof fastpac-induced PVTs are likely...

..Arrhythmia gene therapy is a field in its infancy, and future human applications are dependent on solutions to the problems discussed in this review...

..Magnetic resonance-based visualization of scar morphology would potentially contribute to preprocedural planning for catheter ablation of scar-related, unmappable VT...

..These data advance the development of gene therapy as a potential treatment for common cardiac arrhythmias...

..Arrhythmia gene therapy is a field in its infancy, and future human applications are dependent on solutions to the problems discussed here...

..Historically attributed to blood stasis, little is known about the adverse effects of elevated chamber filling pressure on endocardial function, which could predispose to intracardiac thrombus formation...

..Thus, these results indicate that gene transfer of Gem functions as a genetic calcium channel blocker, the local application of which can effectively modulate cardiac electrical and contractile function...

..A measurable arrhythmic risk even after prolonged shock-free intervals indicates the need for continued ICD therapy in all patients with appropriate ICD indications...

..Challenges facing the field of gene therapy are also reviewed. If these problems can be solved, gene therapy will become a viable alternative for clinical use...

..Adaptation of the method could allow application to other tissue targets. Use with functional proteins in the atria could cure or even prevent diseases such as atrial fibrillation or sinus node dysfunction...

..We have preliminary data showing that gene therapies can eliminate AF. In this proposal, we will further develop our understanding of these therapies and their potential use with AF. ..

..We have preliminary data showing that gene therapies can eliminate AF. In this proposal, we will further develop our understanding of these therapies and their potential use with AF. ..

..Successful completion of these aims will bring gene therapy one-step closer to realizing its potential as a cardiovascular therapeutic. ..

..Successful completion of these aims will provide proof of principle that gene therapy strategies are viable options for the future treatment of common cardiac arrhythmias. ..

..Successful completion of these aims will further our understanding of the mechanism responsible for infarct-related VT and possibly allow translation of these findings into novel therapies. ..