Author: ["Dieter Nuyens","Milan Stengl","Saran Dugarmaa","Tom Rossenbacker","Veerle Compernolle","Yoram Rudy","Jos F. Smits","Willem Flameng","Colleen E. Clancy","Lieve Moons","Marc A. Vos","Mieke Dewerchin","Klaus Benndorf","Désiré Collen","Edward Carmeliet","Peter Carmeliet"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
Deletion of amino-acid residues 1505–1507 (KPQ) in the cardiac SCN5A Na+ channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5AΔ/+) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5aΔ/+ mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5aΔ/+ mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.Cite this article
Nuyens, D., Stengl, M., Dugarmaa, S. et al. Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome. Nat Med 7, 1021–1027 (2001). https://doi.org/10.1038/nm0901-1021 