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1.
Stroke ; 51(10): 3156-3168, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32897811

RESUMO

Understanding the relationship between infection and stroke has taken on new urgency in the era of the coronavirus disease 2019 (COVID-19) pandemic. This association is not a new concept, as several infections have long been recognized to contribute to stroke risk. The association of infection and stroke is also bidirectional. Although infection can lead to stroke, stroke also induces immune suppression which increases risk of infection. Apart from their short-term effects, emerging evidence suggests that poststroke immune changes may also adversely affect long-term cognitive outcomes in patients with stroke, increasing the risk of poststroke neurodegeneration and dementia. Infections at the time of stroke may also increase immune dysregulation after the stroke, further exacerbating the risk of cognitive decline. This review will cover the role of acute infections, including respiratory infections such as COVID-19, as a trigger for stroke; the role of infectious burden, or the cumulative number of infections throughout life, as a contributor to long-term risk of atherosclerotic disease and stroke; immune dysregulation after stroke and its effect on the risk of stroke-associated infection; and the impact of infection at the time of a stroke on the immune reaction to brain injury and subsequent long-term cognitive and functional outcomes. Finally, we will present a model to conceptualize the many relationships among chronic and acute infections and their short- and long-term neurological consequences. This model will suggest several directions for future research.


Assuntos
Aterosclerose/epidemiologia , Infecções/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Aterosclerose/imunologia , Aterosclerose/fisiopatologia , Bacteriemia/epidemiologia , Bacteriemia/imunologia , Bacteriemia/fisiopatologia , Betacoronavirus , Doença Crônica , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/fisiopatologia , Endotélio/fisiopatologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/fisiopatologia , Humanos , Hospedeiro Imunocomprometido/imunologia , Infecções/imunologia , Infecções/fisiopatologia , Inflamação/imunologia , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Humana/fisiopatologia , Pandemias , Ativação Plaquetária , Agregação Plaquetária , Pneumonia/epidemiologia , Pneumonia/imunologia , Pneumonia/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/imunologia , Trombose/epidemiologia , Trombose/imunologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/fisiopatologia
3.
Pediatr Clin North Am ; 67(5): 801-810, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32888682

RESUMO

Syncope and palpitations are common complaints for patients presenting to their primary care provider. They represent symptoms that most often have a benign etiology but rarely can be the first warning sign of a serious condition, such as arrhythmias, structural heart disease, or noncardiac disease. The history, physical examination, and noninvasive testing can, in most cases, distinguish benign from pathologic causes. This article introduces syncope and palpitations, with emphasis on the differential diagnoses, initial presentation, diagnostic strategy, and various management strategies.


Assuntos
Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/fisiologia , Síncope/diagnóstico , Arritmias Cardíacas/fisiopatologia , Criança , Diagnóstico Diferencial , Humanos , Síncope/fisiopatologia
4.
Ann Hematol ; 99(10): 2289-2294, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32737633

RESUMO

Iron overload-induced cardiomyopathy is the leading cause of death in patients with transfusion-dependent thalassemia (TDT). The mortality is extremely high in these patients with severe cardiac complications, and how to rescue them remains a challenge. It is reasonable to use combined chelation with deferiprone (L1) and deferoxamine (DFO) because of their shuttle and synergistic effects on iron chelation. Here, seven consecutive patients with TDT who had severe cardiac complications between 2002 and 2019 and received combined chelation therapy with oral high-dose L1 (100 mg/kg/day) and continuous 24-h DFO infusion (50 mg/kg/day) in our hospital were reported. Survival for eight consecutive patients receiving DFO monotherapy for their severe cardiac complications between 1984 and 2001 was compared. We found that combined chelation therapy with high-dose L1 and DFO was efficient to improve survival and cardiac function in patients with TDT presenting severe cardiac complications. Reversal of arrhythmia to sinus rhythm was noted in all patients. Their 1-month follow-up left ventricular ejection fraction increased significantly (P < 0.001). There were no deaths, and all patients were discharged from hospital with good quality of life. In contrast, all the eight patients receiving DFO monotherapy died (P < 0.001). Accordingly, combined chelation therapy with high-dose L1 and DFO should be considered in patients with TDT presenting cardiac complications.


Assuntos
Arritmias Cardíacas/tratamento farmacológico , Terapia por Quelação/métodos , Deferiprona/uso terapêutico , Desferroxamina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Talassemia/terapia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Transfusão de Sangue , Deferiprona/administração & dosagem , Desferroxamina/administração & dosagem , Avaliação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/etiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Talassemia/complicações , Reação Transfusional , Resultado do Tratamento , Função Ventricular Esquerda
5.
Rev Cardiovasc Med ; 21(2): 205-216, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706209

RESUMO

Sudden cardiac death (SCD) is a rare clinical encounter in pediatrics, but its social impact is immense because of its unpredicted and catastrophic nature in previously healthy individuals. Unlike in adults where the primary cause of SCD is related to ischemic heart disease, the etiology is diverse in young SCD victims. Although certain structural heart diseases may be identified during autopsy in some SCD victims, autopsy-negative SCD is more common in pediatrics, which warrants the diagnosis of sudden arrhythmic death syndrome (SADS) based upon the assumption that the usual heart rhythm is abruptly replaced by lethal ventricular arrhythmia. Despite current advances in molecular genetics, the causes of more than half of SADS cases remain unanswered even after postmortem genetic testing. Moreover, the majority of these deaths occur at rest or during sleep even in the young. Recently, sudden unexpected death in epilepsy (SUDEP) has emerged as another etiology of SCD in children and adults, suggesting critical involvement of the central nervous system (CNS) in SCD. Primary cardiac disorders may not be solely responsible for SCD; abnormal CNS function may also contribute to the unexpected lethal event. In this review article, we provide an overview of the complex pathogenesis of SADS and its diverse clinical presentation in the young and postulate that SADS is, in part, induced by unfortunate miscommunication between the heart and CNS via the autonomic nervous system.


Assuntos
Arritmias Cardíacas/etiologia , Sistema Nervoso Central/fisiopatologia , Morte Súbita Cardíaca/etiologia , Coração/inervação , Morte Súbita Inesperada na Epilepsia/etiologia , Potenciais de Ação , Adolescente , Adulto , Fatores Etários , Animais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Causas de Morte , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Frequência Cardíaca , Humanos , Lactente , Masculino , Medição de Risco , Fatores de Risco , Adulto Jovem
6.
J Vis Exp ; (159)2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32510509

RESUMO

Although advances have been achieved in the treatment of heart failure (HF) following myocardial infarction (MI), HF following MI remains one of the major causes of mortality and morbidity around the world. Cell-based therapies for cardiac repair and improvement of left ventricular function after MI have attracted considerable attention. Accordingly, the safety and efficacy of these cell transplantations should be tested in a preclinical large animal model of HF prior to clinical use. Pigs are widely used for cardiovascular disease research due to their similarity to humans in terms of heart size and coronary anatomy. Therefore, we sought to present an effective protocol for the establishment of a porcine chronic HF model using closed-chest coronary balloon occlusion of the left circumflex artery (LCX), followed by rapid ventricular pacing induced with pacemaker implantation. Eight weeks later, the stem cells were administered by intramyocardial injection in the peri-infarct area. Then the infarct size, cell survival, and left ventricular function (including echocardiography, hemodynamic parameters, and electrophysiology) were evaluated. This study helps establish a stable preclinical large animal HF model for stem cell treatment.


Assuntos
Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Infarto do Miocárdio/complicações , Transplante de Células-Tronco , Células-Tronco/citologia , Animais , Arritmias Cardíacas/fisiopatologia , Sobrevivência Celular , Modelos Animais de Doenças , Ecocardiografia , Estimulação Elétrica , Coração/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Suínos , Função Ventricular Esquerda , Remodelação Ventricular
7.
Am J Physiol Heart Circ Physiol ; 319(2): H251-H261, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559136

RESUMO

Human ether-à-go-go related gene (hERG) K+ channels are important in cardiac repolarization, and their dysfunction causes prolongation of the ventricular action potential, long QT syndrome, and arrhythmia. As such, approaches to augment hERG channel function, such as activator compounds, have been of significant interest due to their marked therapeutic potential. Activator compounds that hinder channel inactivation abbreviate action potential duration (APD) but carry risk of overcorrection leading to short QT syndrome. Enhanced risk by overcorrection of the APD may be tempered by activator-induced increased refractoriness; however, investigation of the cumulative effect of hERG activator compounds on the balance of these effects in whole organ systems is lacking. Here, we have investigated the antiarrhythmic capability of a hERG activator, RPR260243, which primarily augments channel function by slowing deactivation kinetics in ex vivo zebrafish whole hearts. We show that RPR260243 abbreviates the ventricular APD, reduces triangulation, and steepens the slope of the electrical restitution curve. In addition, RPR260243 increases the post-repolarization refractory period. We provide evidence that this latter effect arises from RPR260243-induced enhancement of hERG channel-protective currents flowing early in the refractory period. Finally, the cumulative effect of RPR260243 on arrhythmogenicity in whole organ zebrafish hearts is demonstrated by the restoration of normal rhythm in hearts presenting dofetilide-induced arrhythmia. These findings in a whole organ model demonstrate the antiarrhythmic benefit of hERG activator compounds that modify both APD and refractoriness. Furthermore, our results demonstrate that targeted slowing of hERG channel deactivation and enhancement of protective currents may provide an effective antiarrhythmic approach.NEW & NOTEWORTHY hERG channel dysfunction causes long QT syndrome and arrhythmia. Activator compounds have been of significant interest due to their therapeutic potential. We used the whole organ zebrafish heart model to demonstrate the antiarrhythmic benefit of the hERG activator, RPR260243. The activator abbreviated APD and increased refractoriness, the combined effect of which rescued induced ventricular arrhythmia. Our findings show that the targeted slowing of hERG channel deactivation and enhancement of protective currents caused by the RPR260243 activator may provide an effective antiarrhythmic approach.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Canal de Potássio ERG1/agonistas , Canais de Potássio Éter-A-Go-Go/agonistas , Frequência Cardíaca/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Piperidinas/farmacologia , Quinolinas/farmacologia , Proteínas de Peixe-Zebra/agonistas , Potenciais de Ação , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Cinética , Miócitos Cardíacos/metabolismo , Oócitos , Período Refratário Eletrofisiológico , Transdução de Sinais , Xenopus laevis , Peixe-Zebra , Proteínas de Peixe-Zebra/metabolismo
8.
High Blood Press Cardiovasc Prev ; 27(4): 291-297, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32519207

RESUMO

The implantable cardioverter-defibrillator (ICD) is the most effective therapy to prevent sudden cardiac death (SCD) in high-risk patients. To overcome infections and failure of transvenous leads, the most frightening complications of conventional ICDs, a completely subcutaneous ICD (S-ICD) has been developed and is currently adopted in routine clinical practice. In view of their long life-expectancy, low competitive risk of dying from non-arrhythmic causes, and high lifetime risk of lead-related complications requiring surgical revisions, young patients with cardiomyopathies and inherited arrhythmia syndromes have traditionally been considered ideal candidates for the S-ICD. However, as growing evidence supported S-ICD safety and efficacy, initial niche implant indications were abandoned in favor of a widespread use of this technology, that is currently adopted in common ICD candidates with severe left ventricular dysfunction. Indeed, guidelines recommend S-ICD implantation as an alternative to TV-ICDs in all ICD candidates, unless pacing is required. This review focuses on the contemporary experience with the S-ICD and explores future scenarios in which device-to-device communication will enable to combine leadless therapies.


Assuntos
Arritmias Cardíacas/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Humanos , Desenho de Prótese , Fatores de Risco , Resultado do Tratamento
10.
Cardiovasc Ther ; 2020: 3480276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565909

RESUMO

Wenxin Keli (WXKL) is a traditional Chinese medicine drug approved for the treatment of cardiovascular diseases. This study aimed to identify WXKL-targeting genes involved in antiarrhythmic efficacy of WXKL. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) technology platform was used to screen active compounds of WXKL and WXKL-targeting arrhythmia-related genes. A pig model of myocardial ischemia (MI) was established by balloon-expanding the endothelium of the left coronary artery. Pigs were divided into the model group and WXKL group (n = 6). MI, QT interval, heart rate, and arrhythmia were recorded, and the mRNA expression of target genes in myocardial tissues was detected by PCR. Eleven active ingredients of WXKL and eight WXKL-targeting arrhythmia-related genes were screened. Five pathways were enriched, and an "ingredient-gene-path" network was constructed. WXKL markedly decreased the incidence of arrhythmia in the MI pig model (P < 0.05). The QT interval was significantly shortened, and the heart rate was slowed down in the WXKL group compared with the model group (P < 0.05). In addition, the expression of sodium channel protein type 5 subunit alpha (SCN5A) and beta-2 adrenergic receptor (ADRB2) was downregulated, while muscarinic acetylcholine receptor M2 (CHRM2) was upregulated in the WXKL group (P < 0.05). In conclusion, WXKL may shorten the QT interval and slow down the heart rate by downregulating SCN5A and ADRB2 and upregulating CHRM2 during MI. These findings provide novel insight into molecular mechanisms of WXKL in reducing the incidence of ventricular arrhythmia.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Potenciais de Ação/genética , Animais , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Frequência Cardíaca/genética , Masculino , Medicina Tradicional Chinesa , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Mapas de Interação de Proteínas , Receptor Muscarínico M2/genética , Receptor Muscarínico M2/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Suínos , Porco Miniatura , Fatores de Tempo
14.
Am J Cardiol ; 127: 142-148, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32402485

RESUMO

This study investigated the association between left ventricular ejection fraction (LVEF) and the risk of ventricular arrhythmias (VA), heart transplantation, and death in cardiac sarcoidosis (CS). We identified 110 CS patients meeting 2014 Heart Rhythm Society (HRS) diagnostic criteria with baseline LVEF <35% (n = 32) or ≥35% (n = 78). The primary end point was sustained VA or sudden cardiac death (SCD), and secondary end points included risk of heart transplantation, death, or a composite. Logistic regression determined risk factors for VA/SCD, and Cox proportional hazards regression analysis was performed for secondary end points. Receiver operating curve analysis determined the best discrimination point of LVEF for each end point; sensitivity analyses evaluated the effects of higher LVEF on each end point. Over a follow-up of 2.6 (range 1.0 to 5.8) years, 49 (44.5%) CS patients experienced VA/SCD, including 19 of 32 (59.4%) with LVEF <35%, and 30 of 78 (38.5%) with LVEF ≥35%. After adjustment, LVEF <35% was not significantly associated with an increased risk of VA/SCD compared with LVEF ≥35% (odds ratio 1.3, 95% confidence intervals 0.5 to 3.7). Although LVEF <35% was associated with an increased risk of heart transplantation and death (28.1% vs 12.8%, p = 0.05), this was not significant after adjustment (hazard ratio 1.7, 95% confidence intervals 0.5 to 9.0, p = 0.53). In conclusion, patients with CS experience high rates of VA, SCD, and heart transplantation, even when LVEF is mildly impaired or normal. Patients with LVEF <35% are at particularly elevated risk of VA/SCD. Our findings highlight the imperative to investigate arrhythmia risk in all patients with CS, even in the setting of an otherwise reassuring LVEF.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatias/fisiopatologia , Sarcoidose/fisiopatologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Cardiomiopatias/complicações , Desfibriladores Implantáveis , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Sarcoidose/complicações
16.
Transl Res ; 223: 25-39, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32438072

RESUMO

Chronic obstructive pulmonary disease (COPD) increases the risk of atrial fibrillation (AF), however, its arrhythmogenic mechanisms are unclear. This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. Conventional microelectrode, Western blotting, and histological examinations were performed on PV, left atrium (LA), right atrium, and sinoatrial node (SAN) preparations from control rabbits and those with COPD. The rabbits with COPD had a higher incidence of atrial premature complexes, PV burst firing and delayed afterdepolarizations, higher sympathetic activity, larger LA, and faster PV spontaneous activity than did the control rabbits; but they exhibited a slower SAN beating rate. The LA of the rabbits with COPD had a shorter action potential duration and longer tachyarrhythmia induced by tachypacing (20 Hz) and isoproterenol (1 µM). Additionally, the rabbits with COPD had higher fibrosis in the PVs, LA, and SAN. H89 (10 µM), KN93 (1 µM), and KB-R7943 (10 µM) significantly suppressed burst firing and delayed afterdepolarizations in the PVs of the rabbits with COPD. Moreover, compared with the control rabbits, those with COPD had lower expression levels of the ß1 adrenergic receptor, Cav 1.2, and Na+/Ca2+ exchanger in the PVs; Cav 1.2 in the LA; and hyperpolarization-activated cyclic nucleotide-gated K+ channel 4 in the SAN. COPD increases atrial arrhythmogenesis by modulating the distinctive electrophysiological characteristics of the PVs, LA, and SAN.


Assuntos
Arritmias Cardíacas/complicações , Átrios do Coração/patologia , Doença Pulmonar Obstrutiva Crônica/complicações , Animais , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/fisiopatologia , Modelos Animais de Doenças , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Frequência Cardíaca , Pulmão/fisiopatologia , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Coelhos , Nó Sinoatrial/diagnóstico por imagem , Nó Sinoatrial/fisiopatologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-32357112

RESUMO

Plasticity is a fundamental property of neurons in both the central and peripheral nervous systems, enabling rapid changes in neural network function. The intracardiac nervous system (ICNS) is an extensive network of neurons clustered into ganglionated plexi (GP) on the surface of the heart. GP neurons are the final site of neuronal control of heart rhythm, and pathophysiological remodeling of the ICNS is proposed to feature in multiple cardiovascular diseases, including heart failure and atrial fibrillation. To examine the potential role of GP neuron plasticity in atrial arrhythmia and hypertension, we developed whole cell patch clamp recording techniques from GP neurons in isolated ICNS preparations from aged control (Wistar-Kyoto) and spontaneously hypertensive rats (SHRs). Anesthetized SHRs showed frequent premature ventricular contractions and episodes of atrial arrhythmia following carbachol injection, and isolated SHR atrial preparations were susceptible to pacing induced atrial arrhythmia. Whole cell recordings revealed elevated spontaneous postsynaptic current frequency in SHR GP neurons, as well as remodeled electrophysiology, with significant decreases in action potential amplitude and half-width. SHRs also showed a parallel increase in the number of cholinergic neurons and adrenergic glomus cells in cardiac ganglia, a higher proportion of synaptic α7-subunit but not ß2-containing nicotinic receptors, and an elevation in the number of synaptic terminals onto GP neurons. Our data show that significant structural and functional plasticity occurs in the intracardiac nervous system and suggest that enhanced excitability through synaptic plasticity, together with remodeling of cardiac neuron electrophysiology, contributes to the substrate for atrial arrhythmia in hypertensive heart disease.NEW & NOTEWORTHY We have developed intracardiac neuron whole cell recording techniques in atrial preparations from control and spontaneous hypertensive rats. This has enabled the identification of significant synaptic plasticity in the intracardiac nervous system, including enhanced postsynaptic current frequency, increased synaptic terminal density, and altered postsynaptic receptors. This increased synaptic drive together with altered cardiac neuron electrophysiology could increase intracardiac nervous system excitability and contribute to the substrate for atrial arrhythmia in hypertensive heart disease.


Assuntos
Arritmias Cardíacas/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Coração/inervação , Hipertensão/fisiopatologia , Plasticidade Neuronal/fisiologia , Potenciais de Ação , Animais , Átrios do Coração/fisiopatologia , Neurônios/fisiologia , Técnicas de Patch-Clamp , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
18.
Artigo em Inglês | MEDLINE | ID: mdl-32383994

RESUMO

Cardiac arrhythmias significantly contribute to mortality in Duchenne muscular dystrophy (DMD), a degenerative muscle disease triggered by mutations in the gene encoding for the intracellular protein dystrophin. A major source for the arrhythmias in patients with DMD is impaired ventricular impulse conduction, which predisposes for ventricular asynchrony, decreased cardiac output, and the development of reentrant mechanisms. The reason for ventricular conduction impairments and the associated arrhythmias in the dystrophic heart has remained unidentified. In the present study, we explored the hypothesis that dystrophin-deficient cardiac Purkinje fibers have reduced Na+ currents (INa), which would represent a potential mechanism underlying slowed ventricular conduction in the dystrophic heart. Therefore, by using a Langendorff perfusion system, we isolated Purkinje fibers from the hearts of adult wild-type control and dystrophin-deficient mdx mice. Enhanced green fluorescent protein (eGFP) expression under control of the connexin 40 gene allowed us to discriminate Purkinje fibers from eGFP-negative ventricular working cardiomyocytes after cell isolation. Finally, we recorded INa from wild-type and dystrophic mdx Purkinje fibers for comparison by means of the whole cell patch clamp technique. We found substantially reduced INa densities in mdx compared with wild-type Purkinje fibers, suggesting that dystrophin deficiency diminishes INa. Because Na+ channels in the Purkinje fiber membrane represent key determinants of ventricular conduction velocity, we propose that reduced INa in Purkinje fibers at least partly explains impaired ventricular conduction and the associated arrhythmias in the dystrophic heart.NEW & NOTEWORTHY Dystrophic cardiac Purkinje fibers have abnormally reduced Na+ current densities. This explains impaired ventricular conduction in the dystrophic heart.


Assuntos
Arritmias Cardíacas/metabolismo , Doença do Sistema de Condução Cardíaco/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Ramos Subendocárdicos/metabolismo , Canais de Sódio/metabolismo , Potenciais de Ação/fisiologia , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Doença do Sistema de Condução Cardíaco/complicações , Doença do Sistema de Condução Cardíaco/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/fisiopatologia , Sódio/metabolismo
19.
Arch Cardiovasc Dis ; 113(8-9): 492-502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461091

RESUMO

The population of patients with congenital heart disease (CHD) is continuously increasing, and a significant proportion of these patients will experience arrhythmias because of the underlying congenital heart defect itself or as a consequence of interventional or surgical treatment. Arrhythmias are a leading cause of mortality, morbidity and impaired quality of life in adults with CHD. Arrhythmias may also occur in children with or without CHD. In light of the unique issues, challenges and considerations involved in managing arrhythmias in this growing, ageing and heterogeneous patient population and in children, it appears both timely and essential to critically appraise and synthesize optimal treatment strategies. The introduction of catheter ablation techniques has greatly improved the treatment of cardiac arrhythmias. However, catheter ablation in adults or children with CHD and in children without CHD is more technically demanding, potentially causing various complications, and thus requires a high level of expertise to maximize success rates and minimize complication rates. As French recommendations regarding required technical competence and equipment are lacking in this situation, the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Affiliate Group of Paediatric and Adult Congenital Cardiology have decided to produce a common position paper compiled from expert opinions from cardiac electrophysiology and paediatric cardiology. The paper details the features of an interventional cardiac electrophysiology centre that are required for ablation procedures in adults with CHD and in children, the importance of being able to diagnose, monitor and manage complications associated with ablations in these patients and the supplemental hospital-based resources required, such as anaesthesia, surgical back-up, intensive care, haemodynamic assistance and imaging. Lastly, the need for quality evaluations and French registries of ablations in these populations is discussed. The purpose of this consensus statement is therefore to define optimal conditions for the delivery of invasive care regarding ablation of arrhythmias in adults with CHD and in children, and to provide expert and - when possible - evidence-based recommendations on best practice for catheter-based ablation procedures in these specific populations.


Assuntos
Arritmias Cardíacas/cirurgia , Procedimentos Cirúrgicos Cardíacos , Cardiologistas/normas , Serviço Hospitalar de Cardiologia/normas , Ablação por Cateter/normas , Competência Clínica/normas , Criocirurgia/normas , Cardiopatias Congênitas/cirurgia , Adolescente , Adulto , Fatores Etários , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Criança , Pré-Escolar , Consenso , Criocirurgia/efeitos adversos , Criocirurgia/mortalidade , Técnicas Eletrofisiológicas Cardíacas/normas , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Frequência Cardíaca , Humanos , Lactente , Recém-Nascido , Fatores de Risco , Sobreviventes , Resultado do Tratamento , Adulto Jovem
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