Suchergebnisse

Ventricular fibrillation (VF) during acute myocardial infarction (AMI) is an important contributor to sudden cardiac death. Large animal models are widely used to study AMI-induced arrhythmia, but the mode of AMI induction ranges from thoracotomy and surgical ligation of a coronary vessel (open chest) to minimally invasive techniques, including balloon occlusion (closed chest). How the choice of induction affects arrhythmia development is unclear. The aim of this study was to compare an open-chest and a closed-chest model with regard to hemodynamics, electrophysiology, and arrhythmia development. Forty-two female Danish Landrace pigs (20 open chest, 22 closed chest) were anesthetized, and occlusion of the mid-left anterior descending coronary artery was performed for 60 min. Opening the chest reduced blood pressure and cardiac output (Δ −22 mmHg, Δ −1.5 L/min from baseline, both P < 0.001 intragroup). Heart rate decreased with opening of the chest but increased with balloon placement (P < 0.001). AMI-induced ST elevation was lower in the open-chest group (P < 0.001). Premature ventricular contractions occurred in two distinct phases (0–15 and 15–40 min), the latter of which was delayed in the open-chest group (P = 0.005). VF occurred in 7 out of 20 and 12 out of 22 pigs in the open-chest and closed-chest groups, respectively (P = 0.337), with longer time-to-VF in the open-chest group (23.4 ± 1.2 min in open chest and 17.8 ± 1.4 min in closed chest; P = 0.007). In summary, opening the chest altered hemodynamic parameters and delayed the onset of ventricular arrhythmias. Hence, in the search for mechanisms and novel treatments of AMI-induced arrhythmia, caution should be taken when choosing between or comparing the results from these two models. ; This work was funded by Novo Nordisk Foundation Synergy program (to T. Jespersen and J. Tfelt-Hansen); Hjertecenterts Forskningsudvalg (to S. M. Sattler); and the European Union's Horizon 2020 Research and Innovation Program (ESCAPE-NET) Grant 733381 (to J. ...

Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause of death and treatment options are limited. The aim was to test whether early infusion of amiodarone 10 min after onset of AMI reduced the incidence of VF in a porcine model. Eighteen female Danish landrace pigs were randomized to a control and an amiodarone group. AMI was induced by ligation of the mid-left anterior descending artery for 120 min followed by 60 min of reperfusion. VF occurred in 0/8 pigs treated with amiodarone compared to 7/10 controls (P < 0.01). Amiodarone treatment prolonged RR intervals, reduced dispersion of action potential duration in the infarcted area and mean number of ectopic beats. No negative effects on cardiac output and blood pressure were observed with amiodarone. Amiodarone qualifies as a potential drug candidate to prevent VF in the first minutes to hours of AMI. ; This work was funded by Novo Nordisk Foundation Synergy program (to TJ and JTH); Hjertecentrets Forskningsudvalg (to SMS); German Centre for Cardiovascular Research (DZHK) Partner site Munich (to RW); and European Union's Horizon 2020 research and innovation program under acronym ESCAPE-NET, registered under grant agreement No 733381 (to JTH).

Patients receiving psychiatric medication, like the antipsychotic drug haloperidol, are at an increased risk of sudden cardiac death (SCD). Haloperidol blocks the cardiac rapidly-activating delayed rectifier potassium current, thereby increasing electrical dispersion of repolarization which can potentially lead to arrhythmias. Whether these patients are also at a higher risk to develop SCD during an acute myocardial infarction (AMI) is unknown. AMI locally shortens action potential duration, which might further increase repolarization dispersion and increase the risk of arrhythmia in the presence of haloperidol compared to without. Our aim was to test whether treatment with haloperidol implies an increased risk of SCD when eventually experiencing AMI. Twenty-eight female Danish Landrace pigs were randomized into three groups: low dose haloperidol (0.1 mg/kg), high dose (1.0 mg/kg) or vehicle-control group. One hour after haloperidol/vehicle infusion, AMI was induced by balloon-occlusion of the mid-left anterior descending coronary artery and maintained for 120 min, followed by 60 min of reperfusion. VF occurred during occlusion in 7/11 pigs in the control group, 3/11 in the low dose (p = 0.198) and 2/6 in the high dose group (p = 0.335). High dose haloperidol significantly prolonged QT, and reduced heart rate, vascular resistance and blood pressure before and during AMI. Premature ventricular contractions in phase 1b during AMI were reduced with high dose haloperidol. AMI-induced arrhythmia was not aggravated in pigs with haloperidol treatment. Our results do not suggest that AMI is contributing to the excess mortality in patients treated with antipsychotic drugs seen in epidemiological studies. ; This work was funded by Novo Nordisk Foundation Synergy program (to TJ and JTH); European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No. 733381 (JTH); Hjertecentrets Forskningsudvalg (to SMS).

Background Sudden cardiac death (SCD) constitutes a major health problem worldwide. We investigated whether birth weight (BW), small for gestational age (SGA), and large for gestational age are associated with altered risk of SCD among the young (aged 1–36 years). Methods and Results We included all people born in Denmark from 1973 to 2008 utilizing the Danish Medical Birth Register. All SCDs in Denmark in 2000 to 2009 have previously been identified. We defined 5 BW groups, SGA, and large for gestational age as exposure and SCD as the outcome. We estimated the age‐specific relative risk of SCD with 95% CI. Additionally, we investigated if SGA and large for gestational age are associated with pathological findings at autopsy. The study population for the BW analyses comprised 2 234 501 people with 389 SCD cases, and the SGA and large for gestational age analyses comprised 1 786 281 people with 193 SCD cases. The relative risk for SCD was 6.69 for people with BW between 1500 and 2499 g (95% CI, 2.38–18.80, P<0.001) and 5.89 for people with BW ≥4500 g (95% CI, 1.81–19.12, P=0.003) at age 5 years. BW 2500 to 3400 g was the reference group. Compared with an appropriate gestational age, the relative risk for SGA was 2.85 (95% CI, 1.35–6.00, P=0.006) at age 10 years. For the autopsied cases, the relative risk of sudden arrhythmic death syndrome at age 5 years was 4.19 for SGA (95% CI, 1.08–16.22, P=0.038). Conclusions We found an association between BW and SCD in the young, with an increased risk among SGA infants. In addition, we found an association between SGA and sudden arrhythmic death syndrome. ; This study was funded by the European Union's Horizon 2020 Research and Innovation Programme under the acronym ESCAPE‐NET, registered under grant agreement No. 733381. The work was also supported by Novo Nordisk Foundation No. NFF18OC0031634. The funding sources had no role in the study design, data collection, data analyses, decision to publish, or preparation of the manuscript.

Aims The ESCAPE-NET project ("European Sudden Cardiac Arrest network– towards Prevention, Education and New Effective Treatments") aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods This is an Horizon2020 funded program of the European Union, performed by a European public-private consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum München (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project.

Aims: The ESCAPE-NET project (European Sudden Cardiac Arrest network-towards Prevention, Education and New Effective Treatments) aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods: This is an Horizon2020 funded program of the European Union, performed by a European public-private consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results: The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum Munchen (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion: ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project. (c) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license.

Aims: The ESCAPE-NET project ("European Sudden Cardiac Arrest network– towards Prevention, Education and New Effective Treatments") aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods: This is an Horizon2020 funded program of the European Union, performed by a European publicprivate consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results: The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum München (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion: ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project.