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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2012
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| In: |
Basic research in cardiology
Year: 2012, Jahrgang: 107, Heft: 3, Pages: 265 |
| ISSN: | 1435-1803 |
| DOI: | 10.1007/s00395-012-0265-5 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1007/s00395-012-0265-5 Verlag, Volltext: https://link.springer.com/article/10.1007/s00395-012-0265-5 
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| Verfasserangaben: | Patrick Lugenbiel, Dierk Thomas, Kamilla Kelemen, Kerstin Trappe, Olympia Bikou, Patrick A. Schweizer, Frederik Voss, Rüdiger Becker, Hugo A. Katus, Alexander Bauer |
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| 245 | 1 | 0 | |a Genetic suppression of Gαs protein provides rate control in atrial fibrillation |c Patrick Lugenbiel, Dierk Thomas, Kamilla Kelemen, Kerstin Trappe, Olympia Bikou, Patrick A. Schweizer, Frederik Voss, Rüdiger Becker, Hugo A. Katus, Alexander Bauer |
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| 520 | |a 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-Gαs gene therapy to inactivate Gαs protein or Ad-β-gal as control. Gαs protein inactivation resulted in a 20 % heart rate reduction (P < 0.01). AH and HV intervals were prolonged by 37 ms (P < 0.001) and 28 ms (P < 0.001), respectively, demonstrating atrioventricular conduction delay. Impairment of left ventricular ejection fraction (LVEF) during AF was attenuated by Gαs suppression (LVEF 49 %) compared with controls (LVEF 34 %; P = 0.03). Isoproterenol application accelerated ventricular heart rate from 233 to 281 bpm (P < 0.001) in control animals but did not significantly affect pigs treated with Ad-siRNA-Gαs (192 vs. 216 bpm; P = 0.19). In conclusion, genetic inhibition of Gαs protein in the AV node reduced heart rate and prevented AF-associated reduction of cardiac function in a porcine model. Rate control by gene therapy may provide an alternative to current pharmacological treatment of AF. | ||
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