Genetic suppression of Gαs protein provides rate control in atrial fibrillation

Gene therapy-based modulation of atrioventricular (AV) conduction by overexpression of a constitutively active inhibitory Gα i protein effectively reduced heart rates in atrial fibrillation (AF). However, catecholamine stimulation caused an excessive increase in ventricular rate. We hypothesized tha...

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Bibliographic Details
Published in:Basic research in cardiology 2012-05, Vol.107 (3), p.265-265, Article 265
Main Authors: Lugenbiel, Patrick, Thomas, Dierk, Kelemen, Kamilla, Trappe, Kerstin, Bikou, Olympia, Schweizer, Patrick A., Voss, Frederik, Becker, Rüdiger, Katus, Hugo A., Bauer, Alexander
Format: Article
Language:English
Subjects:
Adrenergic beta-Agonists - administration & dosage
Animals
Atrial Fibrillation - etiology
Atrial Fibrillation - genetics
Atrial Fibrillation - metabolism
Atrial Fibrillation - pathology
Atrial Fibrillation - physiopathology
Atrial Fibrillation - therapy
Atrioventricular Node - metabolism
Atrioventricular Node - pathology
Atrioventricular Node - physiopathology
Cardiac Pacing, Artificial
Cardiology
Disease Models, Animal
Electrocardiography
Fibrosis
Genetic Therapy - adverse effects
Genetic Therapy - methods
GTP-Binding Protein alpha Subunits, Gs - genetics
GTP-Binding Protein alpha Subunits, Gs - metabolism
Heart Rate - drug effects
Heart Rate - genetics
Isoproterenol - administration & dosage
Medicine
Medicine & Public Health
Original Contribution
Pacemaker, Artificial
RNA Interference
RNA, Small Interfering - administration & dosage
Stroke Volume
Sus scrofa
Time Factors
Ventricular Function, Left
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Summary:Gene therapy-based modulation of atrioventricular (AV) conduction by overexpression of a constitutively active inhibitory Gα i protein effectively reduced heart rates in atrial fibrillation (AF). However, catecholamine stimulation caused an excessive increase in ventricular rate. We hypothesized that modest genetic suppression of a stimulatory G protein in the AV node would allow persistent rate control in acute AF and would prevent undesired heart rate acceleration during β-adrenergic activation. Atrial fibrillation was induced in 12 pigs by atrial burst pacing via an implanted cardiac pacemaker. Study animals were then assigned to receive either Ad-siRNA-Gα s gene therapy to inactivate Gα s protein or Ad-β-gal as control. Gα s protein inactivation resulted in a 20 % heart rate reduction ( P  
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-012-0265-5