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.


AIMS: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. METHODS AND RESULTS: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. CONCLUSION: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.


Eur Heart J


European heart journal


Odening KE,Bodi I,Franke G,Rieke R,Ryan de Medeiros A,Perez-Feliz S,Fürniss H,Mettke L,Michaelides K,Lang CN,Steinfurt J,Pantulu ND,Ziupa D,Menza M,Zehender M,Bugger H,Peyronnet R,Behrends JC,Doleschall Z,Zur Hausen




Has Abstract


2019-03-07 00:00:00














  • Effect of revascularizing viable myocardium on left ventricular diastolic function in patients with ischaemic cardiomyopathy.

    abstract:AIMS:In patients with ischaemic left ventricular (LV) dysfunction and viable myocardium, revascularization improves systolic function. Diastolic dysfunction is also present in such patients; however, whether revascularization improves diastolic function also is largely unknown. METHODS:Twenty-six patients with chronic...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Carluccio E,Biagioli P,Alunni G,Murrone A,Leonelli V,Pantano P,Vincenti G,Giombolini C,Ragni T,Reboldi G,Gentile F,Ambrosio G

    更新日期:2009-06-01 00:00:00

  • Aetiology and outcomes of severe right ventricular dysfunction.

    abstract:AIMS:Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. METHODS AND RESUL...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Padang R,Chandrashekar N,Indrabhinduwat M,Scott CG,Luis SA,Chandrasekaran K,Michelena HI,Nkomo VT,Pislaru SV,Pellikka PA,Kane GC

    更新日期:2020-03-21 00:00:00

  • Investigation of impaired coronary vasodilator reserve in the guinea pig heart with pressure induced hypertrophy.

    abstract::Impaired coronary reserve and increased minimal coronary resistance have been documented in several animal models of left ventricular hypertrophy. There is controversy whether the increased minimal coronary resistance is due to vascular or extravascular causes. To test the hypothesis that pressure-overloaded left vent...

    journal_title:European heart journal

    pub_type: 杂志文章,评审


    authors: O'Gorman DJ,Thomas P,Turner MA,Sheridan DJ

    更新日期:1992-05-01 00:00:00

  • Haemodynamic effects of frusemide and its influence on repetitive rapid volume loading in acute myocardial infarction.

    abstract::The haemodynamic effects of intravenous frusemide (1 mg/kg) were studied in 22 male patients with left ventricular failure following acute myocardial infarction. Radiographic pulmonary oedema was present in all patients and their average left heart filling pressure was 20 mmHg. Bolus injection of the drug was followed...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Nelson GI,Ahuja RC,Silke B,Okoli RC,Hussain M,Taylor SH

    更新日期:1983-10-01 00:00:00

  • C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

    abstract:BACKGROUND:There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in par...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Mendall MA,Strachan DP,Butland BK,Ballam L,Morris J,Sweetnam PM,Elwood PC

    更新日期:2000-10-01 00:00:00

  • A stepwise mapping approach for localization and ablation of ectopic right, left, and septal atrial foci using electroanatomic mapping.

    abstract:AIMS:We describe a new strategic stepwise mapping approach for fast and accurate identification and ablation of ectopic atrial foci using an electroanatomic mapping system. METHODS AND RESULTS:Mapping procedures started with the acquisition of four points at the superior/septal part of the tricuspid annulus. According...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Wetzel U,Hindricks G,Schirdewahn P,Dorszewski A,Fleck A,Heinke F,Kottkamp H

    更新日期:2002-09-01 00:00:00

  • Red alert for women's heart: the urgent need for more research and knowledge on cardiovascular disease in women: proceedings of the workshop held in Brussels on gender differences in cardiovascular disease, 29 September 2010.

    abstract::A recent report of the EuroHeart project has shown that women are still underrepresented in many cardiovascular clinical trials, while important gender differences are present within most areas of heart disease. As the burden of cardiovascular disease is increasing in middle-aged women relative to men, a more profound...

    journal_title:European heart journal

    pub_type: 杂志文章,评审


    authors: Maas AH,van der Schouw YT,Regitz-Zagrosek V,Swahn E,Appelman YE,Pasterkamp G,Ten Cate H,Nilsson PM,Huisman MV,Stam HC,Eizema K,Stramba-Badiale M

    更新日期:2011-06-01 00:00:00

  • Identification of pacemaker dependent patients by serial decremental rate inhibition.

    abstract::In a study of the concept of pacemaker dependence, 86 patients who had permanent ventricular demand (VVI) pacemakers implanted for more than six months and were in predominantly paced rhythm underwent repeated interruption of pacing both abruptly and after gradual reduction of paced rate. Non-invasive pace slowing was...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Crick JC,Rokas S,Sowton E

    更新日期:1985-10-01 00:00:00

  • Ventricular premature beats in young subjects without evidence of cardiac disease: histological findings.

    abstract::This report describes the results of right ventricle endomyocardial biopsies from 26 subjects (mean age 27 +/- 10 years) with premature ventricular beats and normal cardiac anatomy and mechanical function. Light microscopy examination revealed normal myocardium in 10 subjects (38%), acute myocarditis in two (7%), bord...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Di Biase M,Chiddo A,Caruso G,Tritto M,Marchese A,Rizzon P

    更新日期:1992-06-01 00:00:00

  • Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study.

    abstract:AIMS:To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. METHODS AND RESULTS:The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged > or =55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence wa...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Bleumink GS,Knetsch AM,Sturkenboom MC,Straus SM,Hofman A,Deckers JW,Witteman JC,Stricker BH

    更新日期:2004-09-01 00:00:00

  • In vivo heating of pacemaker leads during magnetic resonance imaging.

    abstract:AIMS:Magnetic resonance imaging (MRI) is well established as an important diagnostic tool in medicine. However, the presence of a cardiac pacemaker is usually regarded as a contraindication for MRI due to safety reasons. In this study, heating effects at the myocardium-pacemaker lead tip interface have been investigate...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Luechinger R,Zeijlemaker VA,Pedersen EM,Mortensen P,Falk E,Duru F,Candinas R,Boesiger P

    更新日期:2005-02-01 00:00:00

  • Coronary microembolization during early reperfusion: infarct extension, but protection by ischaemic postconditioning.

    abstract:AIMS:Reperfusion injury following acute myocardial infarction impacts not only on the myocardium but also on the coronary microcirculation, and microembolization from the culprit lesion contributes to microvascular obstruction. Prior experimental studies have not accounted for microembolization in ischaemia/reperfusion...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Skyschally A,Walter B,Heusch G

    更新日期:2013-11-01 00:00:00

  • Risk factors for cardiovascular disease in patients with periodontitis.

    abstract:AIMS:This study compared plasma levels of established risk markers for atherosclerosis and indices of inflammation in 50 patients with severe periodontitis to those in 46 healthy cases. METHODS AND RESULTS:Full blood counts were performed and levels of high density lipoproteins (HDL), total cholesterol, haptoglobin, e...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Buhlin K,Gustafsson A,Pockley AG,Frostegård J,Klinge B

    更新日期:2003-12-01 00:00:00

  • Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators.

    abstract:AIMS:To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS:We searched in the Medline, EMBASE, and Cochrane d...

    journal_title:European heart journal

    pub_type: 杂志文章,meta分析,评审


    authors: Brouwer IA,Raitt MH,Dullemeijer C,Kraemer DF,Zock PL,Morris C,Katan MB,Connor WE,Camm JA,Schouten EG,McAnulty J

    更新日期:2009-04-01 00:00:00

  • Angiogenesis in myocardial infarction. An acute or chronic process?

    abstract:BACKGROUND:In the acute phase of myocardial infarction (acute MI) marked endothelial damage occurs within the first 24h following thrombolysis with streptokinase. We investigated whether this is associated with a change in levels of vascular endothelial growth factor (VEGF, possibly marking angiogenesis) in the first 2...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Chung NA,Lydakis C,Belgore F,Blann AD,Lip GY

    更新日期:2002-10-01 00:00:00

  • The 60 minutes myocardial infarction project. Treatment and clinical outcome of patients with acute myocardial infarction in Germany.

    abstract:AIMS:To describe patient characteristics, pre-hospital delay, treatment, complications and outcome in patients with acute myocardial infarction admitted to hospitals in Germany. METHODS AND RESULTS:The study was of prospective observational multicentre design. Those involved were consecutive patients with acute Q-wave...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究


    authors: Rustige J,Schiele R,Burczyk U,Koch A,Gottwik M,Neuhaus KL,Tebbe U,Uebis R,Senges J

    更新日期:1997-09-01 00:00:00

  • Reduced blood pressure-lowering effect of catheter-based renal denervation in patients with isolated systolic hypertension: data from SYMPLICITY HTN-3 and the Global SYMPLICITY Registry.

    abstract:Aims:Catheter-based renal artery denervation (RDN) has been shown to lower blood pressure (BP) in certain patients with uncontrolled hypertension. Isolated systolic hypertension (ISH) (systolic BP [SBP] ≥140 mmHg and diastolic BP <90 mmHg), characterized by increased vascular stiffness, is the predominant hypertensive ...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Mahfoud F,Bakris G,Bhatt DL,Esler M,Ewen S,Fahy M,Kandzari D,Kario K,Mancia G,Weber M,Böhm M

    更新日期:2017-01-07 00:00:00

  • Should we SHIFT our thinking about digoxin? Observations on ivabradine and heart rate reduction in heart failure.

    abstract:AIMS:The importance of heart rate in the pathophysiology of heart failure with reduced LVEF has recently attracted attention. In particular, the findings of the Systolic Heart failure treatment with the I(f) inhibitor ivabradine Trial (SHIFT) have put special emphasis on heart rate reduction with ivabradine for improve...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Castagno D,Petrie MC,Claggett B,McMurray J

    更新日期:2012-05-01 00:00:00

  • Resting and exertional haemodynamic effects of buccal nitroglycerin: acute and chronic discontinuous treatment in post-myocardial infarction patients with heart failure.

    abstract::The resting and exertional haemodynamic effects of acute and chronic discontinuous (one tablet every 6 h) treatment with 5 mg of buccal nitroglycerin (BN) have been assessed in nine postinfarction heart failure patients. At rest, pulmonary artery (PAP), pulmonary wedge (PWP), and right atrial pressures (RAP) were redu...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Opasich C,Riccardi G,Febo O,Tramarin R,Lepore AM,Luca C,Cobelli F,Specchia G

    更新日期:1988-03-01 00:00:00

  • Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis.

    abstract:AIMS:Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Zhang L,Awadalla M,Mahmood SS,Nohria A,Hassan MZO,Thuny F,Zlotoff DA,Murphy SP,Stone JR,Golden DLA,Alvi RM,Rokicki A,Jones-O'Connor M,Cohen JV,Heinzerling LM,Mulligan C,Armanious M,Barac A,Forrestal BJ,Sullivan RJ,

    更新日期:2020-05-07 00:00:00

  • Performance of EuroSCORE in CABG and off-pump coronary artery bypass grafting: single institution experience and meta-analysis.

    abstract:AIMS:To assess EuroSCORE performance in predicting in-hospital mortality in on-pump coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCAB). METHODS AND RESULTS:Additive and logistic EuroSCORE were computed for consecutive patients undergoing CABG (n = 3440, 75%) or OPCAB (n = 1140,...

    journal_title:European heart journal

    pub_type: 杂志文章,meta分析,评审


    authors: Parolari A,Pesce LL,Trezzi M,Loardi C,Kassem S,Brambillasca C,Miguel B,Tremoli E,Biglioli P,Alamanni F

    更新日期:2009-02-01 00:00:00

  • The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome.

    abstract:AIMS:Brugada syndrome is considered to be a distinctive subgroup of idiopathic ventricular fibrillation. Identification of the circadian pattern of ventricular fibrillation would contribute to the elucidation of its underlying pathophysiology, but this pattern remains unknown in patients with Brugada syndrome. METHODS...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Matsuo K,Kurita T,Inagaki M,Kakishita M,Aihara N,Shimizu W,Taguchi A,Suyama K,Kamakura S,Shimomura K

    更新日期:1999-03-01 00:00:00

  • Prospective cohort study of C-reactive protein as a predictor of clinical events in adults with congenital heart disease: results of the Boston adult congenital heart disease biobank.

    abstract:Aims:Despite the well-defined association of high-sensitivity hsCRP with cardiovascular outcomes in apparently healthy adults and those with acquired heart disease, the relevance of this inflammatory marker in adults with congenital heart disease (ACHD) remains unclear. We aimed to examine the clinical correlates and p...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Opotowsky AR,Valente AM,Alshawabkeh L,Cheng S,Bradley A,Rimm EB,Landzberg MJ

    更新日期:2018-09-07 00:00:00

  • Cardiac electrophysiology in New Zealand: a small but vital speciality.

    abstract::Dr Martin Stiles talks about the electrophysiology scene in NZ with Iona MacDonald. ...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: MacDonald I

    更新日期:2012-06-01 00:00:00

  • Influence of captopril on the arterial baroreceptor reflex in patients with heart failure.

    abstract::In 16 male patients with heart failure (NYHA II-III), the influence of a single dose of 25 mg captopril on the carotid sinus baroreceptor reflex was examined. Blood pressure fell significantly by 11 +/- 1.7 mm Hg (P less than 0.001), whereas heart rate remained unchanged (85 +/- 3 vs. 83 +/- 3 beats min-1). Carotid si...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Osterziel KJ,Röhrig N,Dietz R,Manthey J,Hecht J,Kübler W

    更新日期:1988-10-01 00:00:00

  • Dobutamine stress--Doppler echocardiography before and after coronary angioplasty.

    abstract::To determine if dobutamine-induced myocardial ischaemia causes abnormalities in Doppler parameters of left ventricular ejection and filling and to assess early effects of successful coronary angioplasty (PTCA) on these parameters, dobutamine stress echocardiography and Doppler studies were performed once in 11 normal ...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: el-Said ES,Fioretti PM,Roelandt JR,McNeill AJ,Rijsterborgh H,Forster T,Di Mario C,Linker DT

    更新日期:1993-08-01 00:00:00

  • International variation in invasive care of the elderly with acute coronary syndromes.

    abstract:AIMS:To explore variations in invasive care of the elderly with acute coronary syndromes across international practice. METHODS AND RESULTS:Using combined populations from the SYMPHONY and 2nd SYMPHONY trials, we describe 30-day cardiac catheterization in elderly (> or = 75 years; n = 1794) vs. younger patients (< 75 ...

    journal_title:European heart journal

    pub_type: 杂志文章,多中心研究


    authors: Alexander KP,Newby LK,Bhapkar MV,White HD,Hochman JS,Pfisterer ME,Moliterno DJ,Peterson ED,Van de Werf F,Armstrong PW,Califf RM,Symphony and 2nd Symphony Investigators.

    更新日期:2006-07-01 00:00:00

  • Prognostic value of left ventricular volume response during dobutamine stress echocardiography.

    abstract:AIMS:An abnormal left ventricular volume response during dobutamine echocardiography identified patients with severe coronary artery disease. The aim of the study was to assess the prognostic value of left ventricular volume changes during dobutamine stress echocardiography in 136 patients. METHODS AND RESULTS:Endpoin...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Coletta C,Galati A,Ricci R,Sestili A,Guagnozzi G,Re F,Ceci V

    更新日期:1997-10-01 00:00:00

  • Lipoproteins and cardiovascular risk--from genetics to CHD prevention.

    abstract::Increased levels of low density lipoprotein (LDL) cholesterol and triglyceride, and low levels of high density lipoprotein (HDL) cholesterol, are associated with increased risk of coronary heart disease (CHD). Only a minor part of the variation in lipids can be explained by defects in single genes of large effect; the...

    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Cullen P,Funke H,Schulte H,Assmann G

    更新日期:1998-04-01 00:00:00

  • Benefits, challenges, and registerability of the polypill.

    abstract::Guidelines for the management of cardiovascular disease (CVD) stress the importance of treating global risk, rather than individual risk, factors. Patients at high cardiovascular (CV) risk, for example, benefit from a combination of aspirin, antihypertensive agents, lipid-lowering drugs, and possibly folic acid. As th...

    journal_title:European heart journal

    pub_type: 杂志文章,评审


    authors: Sleight P,Pouleur H,Zannad F

    更新日期:2006-07-01 00:00:00