scholarly journals Origin of complex behaviour of spatially discordant alternans in a transgenic rabbit model of type 2 long QT syndrome

2009 ◽  
Vol 587 (19) ◽  
pp. 4661-4680 ◽  
Author(s):  
Ohad Ziv ◽  
Eduardo Morales ◽  
Yoon-kyu Song ◽  
Xuwen Peng ◽  
Katja E. Odening ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Long Qt ◽  
Complex Behaviour ◽  
Transgenic Rabbit ◽  
Qt Syndrome

scholarly journals Alternating Cycle Lengths Increases Dispersion of Action Potential Durations (APD) in Transgenic Rabbit Model of Long QT Syndrome Type 2

2012 ◽  
Vol 102 (3) ◽  
pp. 539a-540a
Author(s):  
Tae Yun Kim ◽  
Paul Jeng ◽  
Chantel Taylor ◽  
JungMin Hwang ◽  
Xuwen Peng ◽  
...  
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Syndrome Type ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Cycle Lengths ◽  
Qt Syndrome

scholarly journals Nicorandil normalizes prolonged repolarisation in the first transgenic rabbit model with Long-QT syndrome 1 both in vitro and in vivo

2011 ◽  
Vol 650 (1) ◽  
pp. 309-316 ◽  
Author(s):  
Jürgen Biermann ◽  
Kezhong Wu ◽  
Katja E. Odening ◽  
Stefan Asbach ◽  
Gideon Koren ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Qt Syndrome

scholarly journals Complex excitation dynamics underlie polymorphic ventricular tachycardia in a transgenic rabbit model of long QT syndrome type 1

Heart Rhythm ◽  
2015 ◽  
Vol 12 (1) ◽  
pp. 220-228 ◽  
Author(s):  
Tae Yun Kim ◽  
Yukiko Kunitomo ◽  
Zachary Pfeiffer ◽  
Divyang Patel ◽  
Jungmin Hwang ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Polymorphic Ventricular Tachycardia ◽  
Syndrome Type ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Qt Syndrome ◽  
Excitation Dynamics

scholarly journals Late I Na Blocker GS967 Supresses Polymorphic Ventricular Tachycardia in a Transgenic Rabbit Model of Long QT Type 2

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Jungmin Hwang ◽  
Tae Yun Kim ◽  
Dmitry Terentyev ◽  
Mingwang Zhong ◽  
Anatoli Y. Kabakov ◽  
...  
Keyword(s):  
Action Potential ◽  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Syndrome Type ◽  
Long Qt ◽  
Repolarization Reserve ◽  
Action Potential Plateau ◽  
Qt Syndrome ◽  
Potential Plateau

Background: Long QT syndrome has been associated with sudden cardiac death likely caused by early afterdepolarizations (EADs) and polymorphic ventricular tachycardias (PVTs). Suppressing the late sodium current (I NaL ) may counterbalance the reduced repolarization reserve in long QT syndrome and prevent EADs and PVTs. Methods: We tested the effects of the selective I NaL blocker GS967 on PVT induction in a transgenic rabbit model of long QT syndrome type 2 using intact heart optical mapping, cellular electrophysiology and confocal Ca 2+ imaging, and computer modeling. Results: GS967 reduced ventricular fibrillation induction under a rapid pacing protocol (n=7/14 hearts in control versus 1/14 hearts at 100 nmol/L) without altering action potential duration or restitution and dispersion. GS967 suppressed PVT incidences by reducing Ca 2+ -mediated EADs and focal activity during isoproterenol perfusion (at 30 nmol/L, n=7/12 and 100 nmol/L n=8/12 hearts without EADs and PVTs). Confocal Ca 2+ imaging of long QT syndrome type 2 myocytes revealed that GS967 shortened Ca 2+ transient duration via accelerating Na + /Ca 2+ exchanger (I NCX )-mediated Ca 2+ efflux from cytosol, thereby reducing EADs. Computer modeling revealed that I NaL potentiates EADs in the long QT syndrome type 2 setting through (1) providing additional depolarizing currents during action potential plateau phase, (2) increasing intracellular Na + (Na i ) that decreases the depolarizing I NCX thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier K + channels (I Ks ), suggesting important roles of I NaL in regulating Na i . Conclusions: Selective I NaL blockade by GS967 prevents EADs and abolishes PVT in long QT syndrome type 2 rabbits by counterbalancing the reduced repolarization reserve and normalizing Na i . Graphic Abstract: A graphic abstract is available for this article.

scholarly journals A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of theKCNE1gene

2016 ◽  
Vol 173 (12) ◽  
pp. 2046-2061 ◽  
Author(s):  
Péter Major ◽  
István Baczkó ◽  
László Hiripi ◽  
Katja E. Odening ◽  
Viktor Juhász ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Dominant Negative ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Dominant Negative Mutation ◽  
Repolarization Reserve ◽  
Qt Syndrome

scholarly journals Different Ventricular Fibrillation (VF) Dynamics in Long QT Syndrome Type 1 vs. 2 in a Transgenic Rabbit Model

2013 ◽  
Vol 104 (2) ◽  
pp. 294a-295a
Author(s):  
Tae Yun Kim ◽  
Jung Min Hwang ◽  
Zachary Pfeiffer ◽  
Yukiko Kunitomo ◽  
Xuwen Peng ◽  
...  
Keyword(s):  
Ventricular Fibrillation ◽  
Long Qt Syndrome ◽  
Rabbit Model ◽  
Syndrome Type ◽  
Long Qt ◽  
Transgenic Rabbit ◽  
Qt Syndrome

scholarly journals A novel KCNH2 frameshift mutation (c.46delG) associated with high risk of sudden death in a family with congenital long QT syndrome type 2

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyun Sok Yoo ◽  
Nancy Medina ◽  
María Alejandra von Wulffen ◽  
Natalia Ciampi ◽  
Analia Paolucci ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Long Qt Syndrome ◽  
Cardiac Death ◽  
Frameshift Mutation ◽  
Alpha Subunit ◽  
Syndrome Type ◽  
Long Qt ◽  
Qt Syndrome ◽  
Congenital Long Qt Syndrome

Abstract Background The congenital long QT syndrome type 2 is caused by mutations in KCNH2 gene that encodes the alpha subunit of potassium channel Kv11.1. The carriers of the pathogenic variant of KCNH2 gene manifest a phenotype characterized by prolongation of QT interval and increased risk of sudden cardiac death due to life-threatening ventricular tachyarrhythmias. Results A family composed of 17 members with a family history of sudden death and recurrent syncopes was studied. The DNA of proband with clinical manifestations of long QT syndrome was analyzed using a massive DNA sequencer that included the following genes: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, ANK2, KCNJ2, CACNA1, CAV3, SCN1B, SCN4B, AKAP9, SNTA1, CALM1, KCNJ5, RYR2 and TRDN. DNA sequencing of proband identified a novel pathogenic variant of KCNH2 gene produced by a heterozygous frameshift mutation c.46delG, pAsp16Thrfs*44 resulting in the synthesis of a truncated alpha subunit of the Kv11.1 ion channel. Eight family members manifested the phenotype of long QT syndrome. The study of family segregation using Sanger sequencing revealed the identical variant in several members of the family with a positive phenotype. Conclusions The clinical and genetic findings of this family demonstrate that the novel frameshift mutation causing haploinsufficiency can result in a congenital long QT syndrome with a severe phenotypic manifestation and an elevated risk of sudden cardiac death.

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