کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2923355 1175871 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Genetic suppression of atrial fibrillation using a dominant-negative ether-a-go-go–related gene mutant
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Genetic suppression of atrial fibrillation using a dominant-negative ether-a-go-go–related gene mutant
چکیده انگلیسی

BackgroundAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Gene therapy–dependent modulation of atrial electrophysiology may provide a more specific alternative to pharmacological and ablative treatment strategies.ObjectiveWe hypothesized that genetic inactivation of atrial repolarizing ether-a-go-go–related gene (ERG) K+ currents using a dominant-negative mutant would provide rhythm control in AF.MethodsTen domestic swine underwent pacemaker implantation and were subjected to atrial burst pacing to induce persistent AF. Animals were then randomized to receive either AdCERG-G627S to suppress ERG/IKr currents or green fluorescent protein (AdGFP) as control. Adenoviruses were applied using a novel hybrid technique combining atrial virus injection and epicardial electroporation to increase transgene expression.ResultsIn pigs treated with AdCERG-G627S, the onset of persistent AF was prevented (n = 2) or significantly delayed compared with AdGFP controls (12 ± 2.1 vs. 6.2 ± 1.3 days; P < .001) during 14-day follow-up. Effective refractory periods were prolonged in the AdCERG-G627S group compared with AdGFP animals (221.5 ± 4.7 ms vs. 197.0 ± 4.7 ms; P < .006). Impairment of left ventricular ejection fraction (LVEF) during AF was prevented by AdCERG-G627S application (LVEFCERG-G627S = 62.1% ± 4.0% vs. LVEFGFP = 30.3% ± 9.1%; P < .001).ConclusionInhibition of ERG function using atrial AdCERG-G627S gene transfer suppresses or delays the onset of persistent AF by prolongation of atrial refractoriness in a porcine model. Targeted gene therapy represents an alternative to pharmacological or ablative treatment of AF.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Heart Rhythm - Volume 9, Issue 2, February 2012, Pages 265–272
نویسندگان
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