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(Circulation. 2009;119:1-4.)
© 2009 American Heart Association, Inc.

Clinical Summaries

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Epicardial Border Zone Overexpression of Skeletal Muscle Sodium Channel SkM1 Normalizes Activation, Preserves Conduction, and Suppresses Ventricular Arrhythmia: An In Silico, In Vivo, In Vitro Study

 
Reentry accounts for 85% of serious tachyarrhythmias complicating ischemic heart disease. Current antiarrhythmic therapies attempt to prevent or treat these arrhythmias by creating bidirectional conduction block, prolonging refractoriness, or both in combination. Implantable defibrillators have had great success in terminating sustained ventricular tachyarrhythmias. However, these therapies possess drawbacks ranging from incomplete arrhythmia suppression to overt toxicity, including proarrhythmia, and the psychological consequence of painful and sometimes inappropriate defibrillation. A key contributor to many reentrant arrhythmias is slow conduction within part of the reentrant circuit such as a myocardial infarct epicardial border zone. We tested the hypothesis that preserving or speeding conduction through the depolarized surviving myocytes within the border zone would be antiarrhythmic. We focally introduced an adenovirus expressing a skeletal muscle sodium channel (SkM1) that mathematical modeling indicated would operate more efficiently at depolarized membrane potentials than the native cardiac sodium channel (SCN5A). SkM1 preserved conduction in the infarct border zone by increasing the maximum upstroke velocity of action potentials, reflected in situ by narrowing of wide or fragmented electrograms. Electrophysiological testing demonstrated that SkM1 administration significantly decreased the incidence of inducible ventricular tachyarrhythmias. This proof-of-concept study provides evidence that preserving or increasing conduction velocity in the infarct border zone by focal delivery of a gene-based therapy such as overexpression of SkM1 is antiarrhythmic. Unlike traditional drugs, gene therapy interventions are not limited to targeting the native channels expressed by cardiomyocytes but allow delivery of foreign channels with more favorable biophysical properties. See p 19.

	Activated Endocannabinoid System in Coronary Artery Disease and Antiinflammatory Effects of Cannabinoid 1 Receptor Blockade on Macrophages

 
Obesity is associated . . . [Full Text of this Article]

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