Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility

内科学 医学 赫尔格 短QT综合征 QT间期 室性心动过速 心脏病学 心室颤动 奎尼丁 后去极化 复极 长QT综合征 内分泌学 电生理学 钾通道
作者
Katja E. Odening,Ilona Bódi,Gerlind Franke,Raphaela Rieke,Anna Ryan de Medeiros,Stefanie Perez‐Feliz,Hannah E. Fürniss,Lea Mettke,Konstantin Michaelides,Corinna N. Lang,Johannes Steinfurt,Naga Deepa Pantulu,David Ziupa,Marius Menza,Manfred Zehender,Heiko Bugger,Rémi Peyronnet,Jan C. Behrends,Zoltán Doleschall,Axel zur Hausen,Christoph Bode,Geneviève Jolivet,Michael Brunner
出处
期刊:European Heart Journal [Oxford University Press]
卷期号:40 (10): 842-853 被引量:42
标识
DOI:10.1093/eurheartj/ehy761
摘要

Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling.Transgenic rabbits were generated by oocyte-microinjection of β-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. Short-QT syndrome 1 and wild type (WT) littermates were subjected to in vivo ECG, electrophysiological studies, magnetic resonance imaging, and ex vivo action potential (AP) measurements. Electrical remodelling was assessed using patch clamp, real-time PCR, and western blot. We generated three SQT1 founders. QT interval was shorter and QT/RR slope was shallower in SQT1 than in WT (QT, 147.8 ± 2 ms vs. 166.4 ± 3, P < 0.0001). Atrial and ventricular refractoriness and AP duration were shortened in SQT1 (vAPD90, 118.6 ± 5 ms vs. 154.4 ± 2, P < 0.0001). Ventricular tachycardia/fibrillation (VT/VF) inducibility was increased in SQT1. Systolic function was unaltered but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged/normalized QT and action potential duration (APD) in SQT1 rabbits by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased-partially reversing the phenotype-while a small increase in IKs may partly contribute to an accentuation of the phenotype.Short-QT syndrome 1 rabbits mimic the human disease phenotype on all levels with shortened QT/APD and increased VT/VF-inducibility and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
hanatae完成签到,获得积分10
刚刚
WDD完成签到,获得积分10
1秒前
张慧完成签到,获得积分10
2秒前
秀丽誉发布了新的文献求助10
2秒前
可爱的函函应助Elody采纳,获得30
3秒前
5秒前
紫紫吃菠菜完成签到,获得积分10
6秒前
雪梅发布了新的文献求助10
7秒前
激昂的逊完成签到,获得积分10
7秒前
Piper发布了新的文献求助10
8秒前
9秒前
科研通AI2S应助英勇的曲奇采纳,获得10
10秒前
10秒前
10秒前
12Q发布了新的文献求助10
11秒前
星辰大海应助阿腾采纳,获得10
11秒前
13秒前
loka完成签到,获得积分10
13秒前
淡然觅荷完成签到 ,获得积分10
15秒前
科研猫发布了新的文献求助10
16秒前
16秒前
量子星尘发布了新的文献求助10
18秒前
19秒前
Owen应助酸奶山茶柚采纳,获得10
21秒前
23秒前
24秒前
周哲发布了新的文献求助10
24秒前
HYT发布了新的文献求助30
25秒前
25秒前
Abby发布了新的文献求助10
27秒前
28秒前
领导范儿应助板栗采纳,获得10
29秒前
ixueyi发布了新的文献求助10
31秒前
wushuang完成签到,获得积分10
36秒前
36秒前
HYT完成签到,获得积分10
40秒前
周哲完成签到 ,获得积分20
42秒前
mashichuang发布了新的文献求助10
42秒前
42秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3976418
求助须知:如何正确求助?哪些是违规求助? 3520512
关于积分的说明 11203586
捐赠科研通 3257127
什么是DOI,文献DOI怎么找? 1798594
邀请新用户注册赠送积分活动 877804
科研通“疑难数据库(出版商)”最低求助积分说明 806523