Abstract：
OBJECTIVE:The K(+) channel encoded by the human ether-a-go-go-related gene (HERG) is crucial for repolarization in the human heart. In order to investigate the impact of HERG current (I(Kr)) on the incidence of cardiac arrhythmias, we generated a transgenic mouse expressing HERG specifically in the heart. METHODS AND RESULTS:ECG recordings at baseline showed no obvious difference between transgenic and wild-type (WT) mice with the exception of the T wave, which was more negative in transgenic mice than in WT mice. E4031 (20 mg/kg) prolonged the QTc interval and flattened the T wave in transgenic mice, but not in WT mice. Injection of BaCl(2) (25 mg/kg) induced short runs of ventricular tachycardia in 9/10 WT mice, but not in transgenic animals. Atrial pacing reproducibly induced atrial tachyarrhythmias in 11/15 WT mice. In contrast, atrial arrhythmia was inducible in only 2/11 transgenic mice. When pretreated with dofetilide (10 mg/kg), transgenic mice were as sensitive to experimental arrhythmias as WT mice. Microelectrode studies showed that atrial action potentials have a steeper slope of duration-rate adaptation in WT than in transgenic mice. Transgenic mice were also characterized by a post-repolarization refractoriness, which could result from the substantial amount of I(Kr) subsisting after repolarization as assessed with action potential-clamp experiments and simulations with a model of the transgenic mouse action potential. CONCLUSION:HERG expression in the mouse heart can protect against experimental induction of arrhythmias. This is the first report of such a protective effect of HERG in vivo.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Royer A,Demolombe S,El Harchi A,Le Quang K,Piron J,Toumaniantz G,Mazurais D,Bellocq C,Lande G,Terrenoire C,Motoike HK,Chevallier JC,Loussouarn G,Clancy CE,Escande D,Charpentier Fdoi
10.1016/j.cardiores.2004.09.030subject
Has Abstractpub_date
2005-01-01 00:00:00pages
128-37issue
1eissn
0008-6363issn
1755-3245pii
S0008-6363(04)00433-Xjournal_volume
65pub_type
杂志文章abstract：:The importance of the vascular adventitia is increasingly being recognized not only in vascular disease but also in normal maintenance and homeostasis of vessels. Activation of the adventitia and its resident fibrocytic cells in response to injury, stretch, cytokines, and hormones has been shown to stimulate different...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2007.06.016
更新日期：2007-09-01 00:00:00
abstract：OBJECTIVE:Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2005.10.019
更新日期：2006-02-01 00:00:00
abstract：BACKGROUND:The mechanism of defibrillation is controversial. Reentry appearing immediately after the shock has been shown to be responsible for defibrillation failure in some studies while other studies have demonstrated that a rapid train of focal activations with the first focus appearing >50 ms after the shock is re...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2003.10.009
更新日期：2004-01-01 00:00:00
abstract：AIMS:Moderate wine consumption is associated with a significant reduction of cardiovascular mortality. The molecular basis of this phenomenon remains unknown. Platelet-derived growth factor (PDGF) is an important contributor to atherogenesis. We investigated the effects of selected red and white wines on PDGF receptor ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn340
更新日期：2009-03-01 00:00:00
abstract：OBJECTIVE:Anoxia followed by reoxygenation (A/R) increases endothelial cell superoxide (O2-) generation which is implicated in E-selectin overexpression. The mechanisms which govern these processes are not fully understood and therefore the goal of our study was to determine the functional importance of NADPH oxidase i...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2004.03.018
更新日期：2004-08-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00221-1
更新日期：1999-01-01 00:00:00
abstract：STUDY OBJECTIVE:The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN:Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); ter...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/24.9.754
更新日期：1990-09-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvx236
更新日期：2018-03-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr250
更新日期：2011-12-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00243-2
更新日期：2002-05-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvq317
更新日期：2011-02-15 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvr078
更新日期：2011-07-15 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvn309
更新日期：2009-05-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/10.2.232
更新日期：1976-03-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00335-8
更新日期：2002-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1093/cvr/cvaa279
更新日期：2020-10-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.11.010
更新日期：2007-02-01 00:00:00
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journal_title：Cardiovascular research
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doi：10.1093/cvr/cvs262
更新日期：2012-12-01 00:00:00
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journal_title：Cardiovascular research
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doi：10.1093/cvr/18.10.604
更新日期：1984-10-01 00:00:00
abstract：OBJECTIVE:The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of thi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/28.6.847
更新日期：1994-06-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/27.1.43
更新日期：1993-01-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvu029
更新日期：2014-04-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvn099
更新日期：2008-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0008-6363(96)00268-4
更新日期：1997-03-01 00:00:00
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journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/16.1.47
更新日期：1982-01-01 00:00:00
abstract：:Papillary muscles isolated from the left ventricle of 17-20 day old Syrian hamsters with genetic cardiomyopathy (BIO 14.6 strain) were examined for their mechanophysiological response to the beta adrenoceptor agonist isoprenaline. The indices of isometric twitch for both myopathic and aged matched normal (BIO RB strai...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/20.8.609
更新日期：1986-08-01 00:00:00
abstract：ABSTRACT:Sepsis accounts for nearly 700 000 deaths in Europe annually and is caused by an overwhelming host response to infection resulting in organ failure. The endothelium is an active contributor to sepsis and as such represents a major target for therapy. During sepsis, endothelial cells amplify the immune response...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvaa070
更新日期：2021-01-01 00:00:00
abstract：OBJECTIVE:The aim was to examine the role of nitric oxide (NO) in the myocardial microcirculation. METHODS:Open chest anaesthetised dogs received intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA; 0.5 mg.kg-1 over 30 min). Myocardial microvascular extraction fraction of a small hydrophilic solute (technetium ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-06-01 00:00:00
abstract：AIMS:This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta. METHODS AND RESULTS:Aortic segments from orchidectomized and control male Sprague-Dawley ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvm059
更新日期：2008-02-01 00:00:00
abstract：OBJECTIVES:We studied the effects of chronic left coronary artery ligation on cardiac structure and function in the mouse. METHODS:Morphometric studies of the left ventricle were performed in coronary artery-ligated and sham-operated animals at one, two, three and five weeks after surgery. The fraction of DNA-synthesi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00216-8
更新日期：1999-03-01 00:00:00
