Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 75
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Pharmacol Res ; 128: 200-210, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29107716

RESUMO

The Pacsin proteins (Pacsin 1, 2 and 3) play an important role in intracellular trafficking and thereby signal transduction in many cells types. This study was designed to examine the role of Pacsin 2 in cardiac development and function. We investigated the development and electrophysiological properties of Pacsin 2 knockout (P2KO) hearts and single cardiomyocytes isolated from 11.5 and 15.5days old fetal mice. Immunofluorescence experiments confirmed the lack of Pacsin 2 protein expression in P2KO cardiac myocytes in comparison to wildtype (WT). Western blotting demonstrates low expression levels of connexin 43 and T-box 3 proteins in P2KO compared to wildtype (WT). Electrophysiology measurements including online Multi-Electrode Array (MEA) based field potential (FP) recordings on isolated whole heart of P2KO mice showed a prolonged AV-conduction time. Patch clamp measurements of P2KO cardiomyocytes revealed differences in action potential (AP) parameters and decreased pacemaker funny channel (If), as well as L-type Ca2+ channel (ICaL), and sodium channel (INa). These findings demonstrate that Pacsin 2 is necessary for cardiac development and function in mouse embryos, which will enhance our knowledge to better understand the genesis of cardiovascular diseases.


Assuntos
Desenvolvimento Embrionário/fisiologia , Coração/fisiologia , Proteínas/fisiologia , Potenciais de Ação , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas do Citoesqueleto , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout
2.
Vasc Med ; 23(5): 419-425, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29985113

RESUMO

The introduction of electronic cigarettes has led to widespread discussion on the cardiovascular risks compared to conventional smoking. We therefore conducted a randomized cross-over study of the acute use of three tobacco products, including a control group using a nicotine-free liquid. Fifteen active smokers were studied during and after smoking either a cigarette or an electronic cigarette with or without nicotine (eGo-T CE4 vaporizer). Subjects were blinded to the nicotine content of the electronic cigarette and were followed up for 2 hours after smoking a cigarette or vaping an electronic cigarette. Peripheral and central blood pressures as well as parameters of arterial stiffness were measured by a Mobil-O-Graph® device. The peripheral systolic blood pressure rose significantly for approximately 45 minutes after vaping nicotine-containing liquid ( p<0.05) and for approximately 15 minutes after smoking a conventional cigarette ( p<0.01), whereas nicotine-free liquids did not lead to significant changes during the first hour of follow-up. Likewise, heart rate remained elevated approximately 45 minutes after vaping an electronic cigarette with nicotine-containing liquid and over the first 30 minutes after smoking a cigarette in contrast to controls. Elevation of pulse wave velocity was independent from mean arterial pressure as well as heart rate in the electronic cigarette and cigarette groups. In this first of its kind trial, we observed changes in peripheral and central blood pressure and also in pulse wave velocity after smoking a cigarette as well as after vaping a nicotine-containing electronic cigarette. These findings may be associated with an increased long-term cardiovascular risk.


Assuntos
Fumar Cigarros/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Hemodinâmica , Nicotina/efeitos adversos , Agonistas Nicotínicos/efeitos adversos , Doença Arterial Periférica/etiologia , Vaping/efeitos adversos , Rigidez Vascular , Adolescente , Adulto , Estudos Cross-Over , Progressão da Doença , Método Duplo-Cego , Feminino , Alemanha , Humanos , Masculino , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Projetos Piloto , Análise de Onda de Pulso , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
3.
Heart Vessels ; 32(7): 856-864, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28116486

RESUMO

Inferior vena cava (IVC) diameter can be used to approximate right atrial pressure in patients admitted for acute decompensated heart failure (ADHF). Recent studies linked IVC dilation to an increased risk of early re-admission and short-term mortality. Moreover, renal insufficiency (RI) is an established risk factor for mortality in ADHF and is associated with congestion. We hypothesized that the IVC diameter is a marker of all-cause mortality but its prognostic impact may be influenced by kidney function. We analyzed data of 1101 patients admitted for ADHF with available echocardiography of the IVC by chart review and death registry linkage. Patients were dichotomized according to a cut-off value of 21 mm. Cox proportional hazards model was used to identify mortality predictors. A dilated IVC was detected in 474 (43.1%) patients. Overall, 400 (36.3%) patients died within 3 years. All-cause mortality was significantly higher in patients with dilated IVC [hazard ratio 1.45 (confidence interval 1.21-1.74); p < 0.001]. However, a dilated IVC was only associated with all-cause mortality in patients with RI function [hazard ratio 1.60 (confidence interval 1.26-2.03); p < 0.001] but not in patients with a preserved kidney function [hazard ratio 1.04 (confidence interval 0.72-1.50); P = 0.84]. IVC diameter was identified as an independent predictor for all-cause mortality in a Cox proportional hazards model with a significant interaction between IVC diameter and baseline kidney function. In conclusion, IVC dilation is a marker of high mortality risk in patients admitted for ADHF. However, this observation was confined to patients with RI.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Mortalidade , Insuficiência Renal/fisiopatologia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Ecocardiografia , Feminino , Alemanha/epidemiologia , Taxa de Filtração Glomerular , Insuficiência Cardíaca/complicações , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Análise Multivariada , Prognóstico , Insuficiência Renal/complicações , Fatores de Risco , Análise de Sobrevida
4.
Cell Physiol Biochem ; 38(2): 646-58, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26849450

RESUMO

BACKGROUND/AIMS: Heart rate variability (HRV) refers to the fluctuation of the time interval between consecutive heartbeats in humans. It has recently been discovered that cardiomyocytes derived from human embryonic and induced pluripotent stem cells show beat rate variability (BRV) that is similar to the HRV in humans. In the present study, clinical aspects of HRV were transferred to an in vitro model. The aims of the study were to explore the BRV in murine embryonic stem cell (mESC)-derived cardiomyocytes and to demonstrate the influence of antiarrhythmic drugs on BRV as has been shown in clinical trials previously. METHODS: The Microelectrode Array (MEA) technique was used to perform short-term recordings of extracellular field potentials (FPs) of spontaneously beating cardiomyocytes derived from mESCs (D3 cell line, αPig-44). Offline analysis was focused on time domain and nonlinear methods. RESULTS: The Poincaré-Plot analysis of measurements without pharmacological intervention revealed that three different shapes of scatter plots occurred most frequently. Comparable shapes have been described in clinical studies before. The antiarrhythmic drugs Ivabradine, Verapamil and Sotalol augmented BRV, whereas Flecainide decreased BRV parameters at low concentrations (SDSD 79.0 ± 8.7% of control at 10(-9) M, p < 0.05) and increased variability measures at higher concentrations (SDNN 258.8 ± 42.7% of control at 10(-5) M, p < 0.05). Amiodarone and Metoprolol did not alter BRV significantly. CONCLUSIONS: Spontaneously beating cardiomyocytes derived from mESCs showed BRV that appears to be similar to the HRV known from humans. Antiarrhythmic drugs affected BRV parameters similar to clinical observations. Therefore, our study demonstrates that this in vitro model can contribute to a better understanding of electrophysiological properties of mESC-derived cardiomyocytes and might serve as a valuable tool for drug safety screening.


Assuntos
Antiarrítmicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Frequência Cardíaca/efeitos dos fármacos , Células-Tronco Embrionárias Murinas/citologia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Diferenciação Celular , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Camundongos , Microeletrodos
6.
Cell Physiol Biochem ; 34(4): 1199-215, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25277677

RESUMO

BACKGROUND/AIMS: In vitro reprogramming of somatic cells holds great potential to serve as an autologous source of cells for tissue repair. However, major difficulties in achieving this potential include obtaining homogeneous and stable cells for transplantation. High electrical activity of cells such as cardiomyocytes (CMs) is crucial for both, safety and efficiency of cell replacement therapy. Moreover, the function of the cardiac pacemaker is controlled by the activities of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here we have examined changes in HCN gene expression and function during cardiomyogenesis. METHODS: We differentiated murine iPS cells selected by an undifferentiated transcription factor 1 (UTF1) -promoter-driven G418 resistance to CMs in vitro and characterized them by RT-PCR, immunocytochemistry, and electrophysiology. RESULTS: As key cardiac markers alpha-actinin and cardiac troponin T could be identified in derived CMs. Immunocytochemical staining of CMs showed the presence of all HCN subunits (HCN1-4). Electrophysiology experiments revealed developmental changes of action potentials and If currents as well as functional hormonal regulation and sensitivity to If channel blockers. CONCLUSION: We conclude that iPS cells derived from UTF-selection give rise to functional CMs in vitro, with established hormonal regulation pathways and functionally expressed If current in a development-dependent manner; and have all phenotypes with the pacemaker as predominant subtype. This might be of great importance for transplantation purposes.


Assuntos
Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Miócitos Cardíacos/metabolismo , Transativadores/genética , Transativadores/metabolismo , Actinina/metabolismo , Potenciais de Ação/genética , Animais , Diferenciação Celular/genética , Linhagem Celular , Camundongos , Regiões Promotoras Genéticas/genética , Troponina T/metabolismo
7.
Nature ; 456(7220): 344-9, 2008 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-18849962

RESUMO

Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.


Assuntos
Células-Tronco Pluripotentes/citologia , Testículo/citologia , Adulto , Animais , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Linhagem da Célula , Células Cultivadas , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Epigênese Genética , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Células-Tronco Pluripotentes/metabolismo , Espermatogônias/citologia , Espermatogônias/ultraestrutura , Teratoma/patologia
8.
Cell Physiol Biochem ; 32(1): 1-10, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23867719

RESUMO

BACKGROUND: The first electrocardiograms (ECGs) have been recorded with a capillary electrometer in the late 19(th) century by John Burdon Sanderson and Augustus Waller. In 1903 Willem Einthoven used the much more sensitive string galvanometer and was awarded Nobel Price in Medicine for this discovery. Though the physical principles of that era are still in use, there have been many advances but also challenges in cardiac electrophysiology over the last decades. One challenge is to record electrocardiograms of rather small animals such as mice and even smaller organisms such as their embryos. As mice belong to the most routinely used laboratory animals it is important to better understand their physiology and specific diseases. We therefore aimed to study whether it is feasible to measure electrical activities of embryonic mouse hearts. METHODS AND RESULTS: For our studies we used substrate-integrated Microelectrode Arrays combined with newly developed stimulation electrodes to perform electrophysiological studies in these hearts. The system enabled us to perform ECG-like recordings with atrio-ventricular (anterograde) and ventriculo-atrial (retrograde) stimulation. The functional separation of atria and ventricles, indicated by a stable atrio-ventricular conduction time, occurred clearly earlier than the morphological separation. Electrical stimulation induced a reversible prolongation of the anterograde and retrograde conduction up to atrio-ventricular conduction blocks at higher frequencies. CONCLUSION: These results yield new insight into functional aspects of murine cardiac development, and may help as a new diagnostic tool to uncover the functional and electrophysiological background of embryonic cardiac phenotypes of genetically altered mice.


Assuntos
Coração/fisiologia , Modelos Animais , Animais , Eletrocardiografia , Embrião de Mamíferos/fisiologia , Desenvolvimento Embrionário/fisiologia , Frequência Cardíaca , Camundongos , Microeletrodos
9.
Vasa ; 42(4): 239-51, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23823856

RESUMO

The aim of this review is to give a contemporary update on renal denervation therapy focusing particularly on the scientific background and present literature as well as on different technical approaches and potential future directions.


Assuntos
Pressão Sanguínea , Hipertensão/cirurgia , Rim/irrigação sanguínea , Simpatectomia/métodos , Animais , Análise Custo-Benefício , Desenho de Equipamento , Custos de Cuidados de Saúde , Humanos , Hipertensão/economia , Hipertensão/fisiopatologia , Simpatectomia/efeitos adversos , Simpatectomia/economia , Simpatectomia/instrumentação , Resultado do Tratamento
10.
J Funct Morphol Kinesiol ; 8(3)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37489314

RESUMO

Cardiovascular health at a young age has implications for preventing cardiovascular disease, and it is associated with improved physical and cognitive performance during the aging process. Sports are well known to prevent cardiovascular disease; however, school-based interventions have mostly been neglected. This cross-sectional study aimed to compare groups of high school students, stratified by the amount of physical activity in their high school curriculum and downtime. Comparisons concerning physical and cognitive performance and arterial stiffness were made. A total of 63 senior-year students were investigated. Arterial stiffness was assessed using the oscillometric technique with ArteriographTM detection. Three-kilometer and pendulum runs were conducted as typical training loads. Cognitive performance was evaluated via the visual and verbal memory and number connection tests. Regarding cognitive skills, extracurricular physical activity improved the number connection test in male participants (p = 0.004). For physical performance, female students with a sports-focused curriculum were faster in the 3 km run (p < 0.001). Concerning arterial stiffness, the measurements yielded a lower mean arterial pressure (p = 0.015) and aortic pulse wave velocity (p = 0.04) in male students with a sports-focused curriculum. In summary, extracurricular physical activity and enrollment in a sports-focused curriculum may be associated with lower cardiovascular risk due to lower arterial stiffness and better physical and cognitive abilities.

11.
J Mol Cell Cardiol ; 53(3): 401-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22728218

RESUMO

Electrophysiological maturation and integration of transplanted cardiomyocytes are essential to enhance safety and efficiency of cell replacement therapy. Yet, little is known about these important processes. The aim of our study was to perform a detailed analysis of electrophysiological maturation and integration of transplanted cardiomyocytes. Fetal cardiomyocytes expressing enhanced green fluorescent protein were transplanted into cryoinjured mouse hearts. At 6, 9 and 12 days after transplantation, viable slices of recipient hearts were prepared and action potentials of transplanted and host cardiomyocytes within the slices were recorded by microelectrodes. In transplanted cells embedded in healthy host myocardium, action potential duration at 50% repolarization (APD50) decreased from 32.2 ± 3.3 ms at day 6 to 27.9 ± 2.6 ms at day 9 and 19.6 ± 1.6 ms at day 12. The latter value matched the APD50 of host cells (20.5 ± 3.2 ms, P=0.78). Integration improved in the course of time: 26% of cells at day 6 and 53% at day 12 revealed no conduction blocks up to a stimulation frequency of 10 Hz. APD50 was inversely correlated to the quality of electrical integration. In transplanted cells embedded into the cryoinjury, which showed no electrical integration, APD50 was 49.2 ± 4.3 ms at day 12. Fetal cardiomyocytes transplanted into healthy myocardium integrate electrically and mature after transplantation, their action potential properties after 12 days are comparable to those of host cardiomyocytes. Quality of electrical integration improves over time, but conduction blocks still occur at day 12 after transplantation. The pace of maturation correlates with the quality of electrical integration. Transplanted cells embedded in cryoinjured tissue still possess immature electrophysiological properties after 12 days.


Assuntos
Coração/fisiologia , Miocárdio/metabolismo , Miócitos Cardíacos/fisiologia , Potenciais de Ação , Animais , Masculino , Camundongos , Miocárdio/citologia , Miócitos Cardíacos/transplante , Fatores de Tempo
12.
Cell Physiol Biochem ; 29(5-6): 819-32, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22613982

RESUMO

BACKGROUND/AIMS: Cardiac dysfunction is one of the main cause of drug candidate failures in the preclinical and/or clinical studies and responsible for the retraction of large number of drugs from the market. The prediction of arrhythmic risk based on preclinical trials during drug development remains limited despite intensive and costly investigation. Moreover, methods for analyzing beating behavior of cardiomyocytes (CMs) in culture to diagnose arrhythmias are not well developed. METHODS: In this study, we combined two emerging technologies, induced pluripotent stem (iPS) cell-derived CMs and impedance-based real-time (xCELLigence RTCA Cardio Instrument) monitoring of CM electrical activity, to assess the effect of drugs known affect cardiac activity such as isoproterenol, carbachol, terfenadine, sotalol and doxorubicin. Cells were exposed to a drug in a single dose or repeated dose scenarios and data were analyzed using RTCA Cardio software, Poincaré plot and detrended fluctuation analysis. RESULTS: The results revealed significant changes in beating parameters of iPS-CMs induced by reference compounds. Heptanol, gap junction blocker, completely disrupted the synchronous beating pattern of iPS-CMs. Decrease of beating rate, amplitude and beat-to-beat signal variations of iPS-CMs monolayer observed in the presence of doxorubicin revealed severe abnormality detected by the system. Additionally, the irregular beating rhythms recorded in the presence of Terfenadine and Sotalol at high concentration, reflect abnormalities in cell contraction and/or relaxation which may lead to arrhythmia. CONCLUSIONS: All these results indicated that xCELLigence RTCA Cardio system combined with iPS cells, has the potential to be an attractive high-throughput tool for studying CMs during prolonged culture times and to screen potential drugs for cardiotoxic side effects.


Assuntos
Antiarrítmicos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Coração/efeitos dos fármacos , Modelos Teóricos , Animais , Carbacol/farmacologia , Linhagem Celular , Doxorrubicina/farmacologia , Eletrodos , Imuno-Histoquímica , Técnicas In Vitro , Isoproterenol/farmacologia , Camundongos , Técnicas de Patch-Clamp , Sotalol/farmacologia , Terfenadina/farmacologia
13.
Biochem Biophys Res Commun ; 418(1): 74-80, 2012 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-22252295

RESUMO

BACKGROUND: Prevailing data suggest that ATP-sensitive potassium channels (K(ATP)) contribute to a surprising resistance to hypoxia in mammalian embryos, thus we aimed to characterize the developmental changes of K(ATP) channels in murine fetal ventricular cardiomyocytes. METHODS: Patch clamp was applied to investigate the functions of K(ATP). RT-PCR, Western blot were used to further characterize the molecular properties of K(ATP) channels. RESULTS: Similar K(ATP) current density was detected in ventricular cardiomyocytes of late development stage (LDS) and early development stage (EDS). Molecular-biological study revealed the upregulation of Kir6.1/SUR2A in membrane and Kir6.2 remained constant during development. Kir6.1, Kir6.2, and SUR1 were detectable in the mitochondria without marked difference between EDS and LDS. Acute hypoxia-ischemia led to cessation of APs in 62.5% of tested EDS cells and no APs cessation was observed in LDS cells. SarcK(ATP) blocker glibenclamide rescued 47% of EDS cells but converted 42.8% of LDS cells to APs cessations under hypoxia-ischemic condition. MitoK(ATP) blocker 5-HD did not significantly influence the response to acute hypoxia-ischemia at either EDS or LDS. In summary, sarcK(ATP) played distinct functional roles under acute hypoxia-ischemic condition in EDS and LDS fetal ventricular cardiomyocytes, with developmental changes in sarcK(ATP) subunits. MitoK(ATP) were not significantly involved in the response of fetal cardiomyocytes to acute hypoxia-ischemia and no developmental changes of K(ATP) subunits were found in mitochondria.


Assuntos
Ventrículos do Coração/embriologia , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/fisiologia , Canais de Potássio/metabolismo , Transportadores de Cassetes de Ligação de ATP/agonistas , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Hipóxia Celular , Ventrículos do Coração/metabolismo , Canais KATP/agonistas , Canais KATP/genética , Canais KATP/metabolismo , Moduladores de Transporte de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos , Miócitos Cardíacos/metabolismo , Pinacidil/farmacologia , Canais de Potássio/agonistas , Canais de Potássio/genética , Canais de Potássio Corretores do Fluxo de Internalização/agonistas , Canais de Potássio Corretores do Fluxo de Internalização/genética , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptores de Droga/agonistas , Receptores de Droga/genética , Receptores de Droga/metabolismo , Receptores de Sulfonilureias
14.
Europace ; 14(12): 1764-70, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22753865

RESUMO

AIMS: A considerable number of lead defects occurs during long-term cardioverter defibrillator therapy. Evidence-based strategies for the handling of chronically implanted, non-functional high-voltage (HV) leads are mandatory. METHODS AND RESULTS: Patient outcome after abandonment of HV leads was retrospectively compared with patient outcome following other lead revision strategies and following primary implantation. A total of 903 consecutive patients undergoing 997 implantable cardioverter defibrillator (ICD) implantations or lead revisions were followed for a mean period of 48.8 ± 37.8 months. One or more additional HV leads were placed in 60 patients. An additional pace/sense lead was implanted in 13 patients. Extraction and replacement of a dysfunctional HV lead was performed in 21 patients. The overall rate of complications including artefact sensing, ineffective defibrillation, symptomatic subclavian vein thrombosis, and other lead defects did not differ between patients with and without an additional HV lead (10.0 vs. 8.9%, P = 0.32). Survival without lead associated complications did not differ between groups. Results remained unchanged after correction for covariates. CONCLUSIONS: Abandoned HV leads did not increase the risk of ICD system-related complications in the majority of patients. Thus, a general lead extraction policy of dysfunctional HV leads cannot be advised in an average ICD population. Recommendations may not apply for young and physically active patients, in whom HV lead extraction must be considered.


Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Remoção de Dispositivo/mortalidade , Eletrodos Implantados/estatística & dados numéricos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/prevenção & controle , Sistema de Registros , Trombose Venosa/mortalidade , Idoso , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Falha de Prótese , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida
15.
Pacing Clin Electrophysiol ; 35(8): 943-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22650352

RESUMO

BACKGROUND: Cardiac resynchronization therapy (CRT) is an established method in patients with severe heart failure and wide QRS configuration, particularly during sinus rhythm (SR). In CRT patients with permanent atrial fibrillation (AF), there is no general consensus regarding the need for atrioventricular node (AVN) ablation. The aim of this study was to evaluate the benefit of CRT in permanent AF with and without AVN ablation. METHODS: New York Heart Association classification, QRS duration, and echocardiographic parameters were assessed before and after CRT with a follow-up of 12 ± 3 months. Two hundred thirty patients in SR and 46 patients with permanent AF of 2.1 ± 0.5 years duration were studied. AVN ablation was performed only in AF patients with insufficient pharmacological rate control evidenced by ≤80 % ventricular stimulation. RESULTS: Fifteen AF patients underwent AVN ablation. Biventricular pacing comparably improved functional status, left ventricular ejection fraction, and left ventricular end-diastolic dimensions in all treated groups. Biventricular stimulation percentage was 10% lower in pharmacologically treated AF patients over 1 year as compared to patients in SR and to AF patients undergoing AVN ablation, which did not affect outcome in this patient population. CONCLUSION: In patients with permanent AF and CRT, an AVN ablation strategy might not be strictly required in all patients.


Assuntos
Fibrilação Atrial/terapia , Terapia de Ressincronização Cardíaca/métodos , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/cirurgia , Nó Atrioventricular/cirurgia , Ablação por Cateter/métodos , Eletrocardiografia , Feminino , Átrios do Coração/cirurgia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Biomed Pharmacother ; 146: 112589, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34968926

RESUMO

BACKGROUND: The human heart rhythm can be quantified by analyzing the heart rate variability (HRV). A major influencing factor of the HRV is the circadian rhythm. The ocular light and the hormone melatonin play decisive roles in the circadian rhythm. The beat rate variability (BRV) is considered to be the in vitro equivalent of the HRV. Previous studies have demonstrated the influence of melatonin on cardiomyocytes. Also, the influence of light on cardiomyocytes has been described before. Nevertheless, the effect of light on the BRV of cardiomyocytes has not yet been examined. MATERIAL AND METHODS: The BRV of spontaneously beating cardiomyocytes was measured with microelectrode arrays over a time period of 30 min. The experiments were either performed with light exposure (with and without an infrared filter) or in complete darkness. RESULTS: The BRV was higher and the beating frequency was lower when the cardiomyocytes were exposed to the full spectrum of light, compared to the measurements in darkness as well as to the measurements with an infrared filter. In contrast, the differences of BRV between the measurements in darkness and the measurements with an infrared filter were not as distinct. CONCLUSIONS: This is the first study demonstrating the influence of light on the beating rhythm of heart tissue in vitro. The results indicate that especially the infrared spectrum of light alters the BRV. These findings could be of interest for clinical applications such as the field of optical pacing as well as in neonatal patient care.


Assuntos
Células-Tronco Embrionárias , Frequência Cardíaca/fisiologia , Luz , Animais , Camundongos , Miócitos Cardíacos
17.
Life (Basel) ; 12(11)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36362851

RESUMO

(1) Background: watching sporting events may trigger cardiovascular events by elevating emotional stress levels. The underlying reasons and specific populations at risk are not well defined. (2) Methods: we conducted a multicenter prospective trial at three German sites during the UEFA Soccer EC 2012 and 2021 comprising 52 healthy participants (noCVD) and 18 patients hospitalized with cardiovascular disease (CVD). Subjects were studied during matches of the German national team (GP) as well as corresponding matches without German participation (noGP). Peripheral and central blood pressure (BP) and parameters of arterial stiffness were measured (Mobil-O-Graph™, I.E.M., Stolberg, Germany) before, during, and after the matches. (3) Results: in terms of CVD, peripheral as well as central BP and heart rate increased significantly during GP as well as noGP matches and remained elevated beyond the end of the matches. Likewise, arterial stiffness parameters and vascular resistance were higher during the matches and remained elevated after the matches. No consistent significant differences were found between GP and noGP matches. (4) Conclusions: this is the first study on real-life changes in hemodynamics during sport-associated emotional stress, with comparison between noCVD and CVD. We found that alterations were profound in CVD and remained elevated even after the matches.

18.
FASEB J ; 24(8): 2739-51, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20371616

RESUMO

Cardiomyocytes generated from embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells are suggested for repopulation of destroyed myocardium. Because contractile properties are crucial for functional regeneration, we compared cardiomyocytes differentiated from ES cells (ESC-CMs) and iPS cells (iPS-CMs). Native myocardium served as control. Murine ESCs or iPS cells were differentiated 11 d in vitro and cocultured 5-7 d with irreversibly injured myocardial tissue slices. Vital embryonic ventricular tissue slices of similar age served for comparison. Force-frequency relationship (FFR), effects of Ca(2+), Ni(2+), nifedipine, ryanodine, beta-adrenergic, and muscarinic modulation were studied during loaded contractions. FFR was negative for ESC-CMs and iPS-CMs. FFR was positive for embryonic tissue and turned negative after treatment with ryanodine. In all groups, force of contraction and relaxation time increased with the concentration of Ca(2+) and decreased with nifedipine. Force was reduced by Ni(2+). Isoproterenol (1 microM) increased the force most pronounced in embryonic tissue (207+/-31%, n=7; ESC-CMs: 123+/-5%, n=4; iPS-CMs: 120+/-4%, n=8). EC(50) values were similar. Contractile properties of iPS-CMs and ESC-CMs were similar, but they were significantly different from ventricular tissue of comparable age. The results indicate immaturity of the sarcoplasmic reticulum and the beta-adrenergic response of iPS-CMs and ESC-CMs.


Assuntos
Células-Tronco Embrionárias/citologia , Ventrículos do Coração/citologia , Células-Tronco Pluripotentes Induzidas/citologia , Contração Miocárdica , Miócitos Cardíacos/citologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Fenômenos Biomecânicos , Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio , Técnicas de Cultura de Células , Diferenciação Celular , Técnicas de Cocultura , Camundongos , Nifedipino/farmacologia , Retículo Sarcoplasmático
19.
Biochem Pharmacol ; 192: 114746, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34461117

RESUMO

Long QT syndrome (LQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT) are genetic diseases of the heart caused by mutations in specific cardiac ion channels and are characterized by paroxysmal arrhythmias, which can deteriorate into ventricular fibrillation. In LQTS3 and BrS different mutations in the SCN5A gene lead to a gain-or a loss-of-function of the voltage-gated sodium channel Nav1.5, respectively. Although sharing the same gene mutation, these syndromes are characterized by different clinical manifestations and functional perturbations and in some cases even present an overlapping clinical phenotype. Several studies have shown that Na+ current abnormalities in LQTS3 and BrS can also cause Ca2+-signaling aberrancies in cardiomyocytes (CMs). Abnormal Ca2+ homeostasis is also the main feature of CPVT which is mostly caused by heterozygous mutations in the RyR2 gene. Large numbers of disease-causing mutations were identified in RyR2 and SCN5A but it is not clear how different variants in the SCN5A gene produce different clinical syndromes and if in CPVT Ca2+ abnormalities and drug sensitivities vary depending on the mutation site in the RyR2. These questions can now be addressed by using patient-specific in vitro models of these diseases based on induced pluripotent stem cells (iPSCs). In this review, we summarize different insights gained from these models with a focus on electrophysiological perturbations caused by different ion channel mutations and discuss how will this knowledge help develop better stratification and more efficient personalized therapies for these patients.


Assuntos
Canalopatias/genética , Fenômenos Eletrofisiológicos/fisiologia , Cardiopatias/genética , Células-Tronco Pluripotentes Induzidas/fisiologia , Mutação/genética , Miócitos Cardíacos/fisiologia , Animais , Canalopatias/patologia , Canalopatias/fisiopatologia , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Células-Tronco Pluripotentes Induzidas/patologia , Miócitos Cardíacos/patologia
20.
Biomed Pharmacother ; 136: 111245, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33450496

RESUMO

BACKGROUND: In healthy individuals, a major factor influencing the heart rate variability (HRV) is the circadian rhythm. The role of melatonin as an essential component of the circadian rhythm in the adult human organism and the beneficial effects of a treatment with melatonin during the fetal period is well described. Toxic effects of melatonin are discussed less frequently. Since pharmacological studies cannot be carried out on pregnant women, the establishment of an equivalent in vitro model is important. We therefore tested whether melatonin can influence the beat rate variability (BRV) of spontaneously beating cardiomyocytes derived from murine embryonic stem cells (mESCs) and whether melatonin exhibits toxic effects in this in vitro model. METHODS: Microelectrode Arrays recorded extracellular field potentials of spontaneously beating cardiomyocytes. Melatonin was applied in a concentration range from 10-11 M to 10-5 M. The analysis of the BRV focused on time domain methods. RESULTS: In line with clinical observations, melatonin decreased the beating frequency and increased the BRV. The effect of melatonin up to a concentration of 10-6 M was reversible, whereas the application of higher concentrations induced an irreversible effect. CONCLUSION: The study underlines the potential of this in vitro model to help explore the development of circadian rhythms and their modulation by melatonin in the embryonic phase. The results imply that melatonin influences the heart rhythm as early as during the embryonic heart development. Furthermore, the results indicate a potentially toxic effect of melatonin that has not been described in detail before.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Melatonina/farmacologia , Células-Tronco Embrionárias Murinas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Potenciais de Ação , Animais , Diferenciação Celular , Linhagem Celular , Relação Dose-Resposta a Droga , Melatonina/toxicidade , Camundongos , Células-Tronco Embrionárias Murinas/fisiologia , Miócitos Cardíacos/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA