Cell Therapy for Rate Control in Atrial Fibrillation

Autologous Dermal Fibroblast Injections Slow Atrioventricular Conduction and Ventricular Rate in Atrial Fibrillation in Swine

“…[23][24][25][26][27] Although previous studies have reported the effects of ADF on myocardial conduction, including the AVN and focusing principally on conduction velocity, [20][21][22][23][24][25][26][27] no previous studies have addressed the critical safety concern of high-grade AV block excluded by the extended and continuous rhythm monitoring in the present study. The putative mechanisms for the effect of the transplanted ADFs in retarding AV conduction include collagenous interruption of the myocardial syncytium and cell separation, and myocyte-fibroblast gapjunctional coupling providing an alternative sink for charge transfer between cardiac myocytes.…”

“…Fibroblasts were grown to 80% confluence then passaged. 22 Passage 2 to 4 was used for cell injections. Before injection, fibroblasts were labeled with CM-DiI 2μl/mL (Invitrogen, Carlsbad, CA).…”

“…19,20 Cellular therapies have the potential to either enhance or block electric conduction of the heart, 21,22 and although dermal fibroblasts injected in the AVN area have been shown to modify conduction velocity, 21 the clinical therapeutic goal in AF is not that of slowing AV nodal conduction, but of controlling ventricular response rate. The aim of this study was to address the hypothesis that injections of adult autologous dermal fibroblasts (ADF) in the AVN area would inhibit AVN conduction, resulting in control of ventricular response during AF without inducing complete AV block or evidence of fibrotic changes in the lung.…”

The Use of Gene Therapy for Ablation of Atrial Fibrillation

“…Rate controlling drugs are largely successful mainstays of therapy, but their use is limited in some patients by inadequate efficacy or intolerable side effects. 78,79 Patients with AV node ablation are permanently dependent on pacemaker, and they have loss of synchronous left ventricular contraction that can be partially relieved by biventricular pacing, again requiring more implanted hardware. As a proof-of-concept, the inhibitory G-protein α-subunit (Gαi2) was incorporated into Ad and transferred to porcine AV node.…”