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2.
Pediatr Cardiol ; 40(5): 1035-1040, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31065756

RESUMO

Tricuspid valve regurgitation (TR) increases adverse outcomes in children with hypoplastic left heart syndrome (HLHS). Changes in tricuspid valve (TV) annulus and leaflet geometry have been described but the underlying causes for TR in HLHS remain uncertain. We aimed to examine the association between left ventricular (LV) size and TR in infants with HLHS as right ventricular (RV)-LV interactions may be important in TR development. Echocardiograms of 50 infants with HLHS were reviewed. LV size, RV function, TR grade, TV annulus z-score, and aortic arch obstruction were examined at birth and 1 year of age (or the latest study post-bidirectional Glenn anastomosis if the patient was < 1 year of age). 24/50 (48%) had severe LV hypoplasia and 26/50 (52%) had mild/moderate LV hypoplasia. At 1 year, 10/24 (42%) with severe LV hypoplasia had moderate/severe TR versus 0/26 in the mild/moderate LV hypoplasia group (p = 0.0002). TR progressed ( ≥ 1 grade) in 14/24(58%) with severe LV hypoplasia versus 5/26 (19%) with mild/moderate LV hypoplasia (p = 0.008). In this cohort, no association was found between the degree of TR and either RV function, TV annular z-score, or arch obstruction; or between the degree of LV hypoplasia and either RV function or TV annular z-score. In infants with HLHS, the severity and progression of TR is associated with the severity of LV hypoplasia. The mechanism for this association needs further exploration but suggests a role for RV-LV interactions in the development of TR.


Assuntos
Síndrome do Coração Esquerdo Hipoplásico/complicações , Insuficiência da Valva Tricúspide/etiologia , Criança , Ecocardiografia , Feminino , Idade Gestacional , Ventrículos do Coração/patologia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico por imagem , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Lactente , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Função Ventricular Direita
3.
Nat Commun ; 10(1): 1802, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30996254

RESUMO

The primary cause of heart failure is the loss of cardiomyocytes in the diseased adult heart. Previously, we reported that the miR-17-92 cluster plays a key role in cardiomyocyte proliferation. Here, we report that expression of miR-19a/19b, members of the miR-17-92 cluster, is induced in heart failure patients. We show that intra-cardiac injection of miR-19a/19b mimics enhances cardiomyocyte proliferation and stimulates cardiac regeneration in response to myocardial infarction (MI) injury. miR-19a/19b protected the adult heart in two distinctive phases: an early phase immediately after MI and long-term protection. Genome-wide transcriptome analysis demonstrates that genes related to the immune response are repressed by miR-19a/19b. Using an adeno-associated virus approach, we validate that miR-19a/19b reduces MI-induced cardiac damage and protects cardiac function. Finally, we confirm the therapeutic potential of miR-19a/19b in protecting cardiac function by systemically delivering miR-19a/19b into mice post-MI. Our study establishes miR-19a/19b as potential therapeutic targets to treat heart failure.


Assuntos
Terapia Genética/métodos , Insuficiência Cardíaca/patologia , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Infarto do Miocárdio/terapia , Animais , Proliferação de Células/genética , Dependovirus/genética , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Insuficiência Cardíaca/terapia , Ventrículos do Coração/patologia , Humanos , Injeções Intralesionais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Miócitos Cardíacos/fisiologia , Regeneração/genética
4.
Sensors (Basel) ; 19(8)2019 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-31013869

RESUMO

Automatic detection of left ventricle myocardium is essential to subsequent cardiac image registration and tissue segmentation. However, it is considered challenging mainly because of the complex and varying shape of the myocardium and surrounding tissues across slices and phases. In this study, a hybrid model is proposed to detect myocardium in cardiac magnetic resonance (MR) images combining region proposal and deep feature classification and regression. The model firstly generates candidate regions using new structural similarity-enhanced supervoxel over-segmentation plus hierarchical clustering. Then it adopts a deep stacked sparse autoencoder (SSAE) network to learn the discriminative deep feature to represent the regions. Finally, the features are fed to train a novel nonlinear within-class neighborhood preserved soft margin support vector (C-SVC) classifier and multiple-output support vector ( ε -SVR) regressor for refining the location of myocardium. To improve the stability and generalization, the model also takes hard negative sample mining strategy to fine-tune the SSAE and the classifier. The proposed model with impacts of different components were extensively evaluated and compared to related methods on public cardiac data set. Experimental results verified the effectiveness of proposed integrated components, and demonstrated that it was robust in myocardium localization and outperformed the state-of-the-art methods in terms of typical metrics. This study would be beneficial in some cardiac image processing such as region-of-interest cropping and left ventricle volume measurement.


Assuntos
Técnicas de Imagem Cardíaca , Ventrículos do Coração/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Miocárdio/patologia , Ventrículos do Coração/patologia , Humanos , Imagem por Ressonância Magnética/tendências , Máquina de Vetores de Suporte
5.
Blood Coagul Fibrinolysis ; 30(3): 96-103, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864962

RESUMO

: Left ventricular thrombus (LVT) is a commonly seen complication of myocardial infarction and it also can be seen because of hypertrophic cardiomyopathies, nonischemic dilated cardiomyopathies, malignancies, and so on. Guidelines suggest the use of warfarin for left ventricular thrombi, but recent case reports show that direct oral anticoagulants (DOACs) are beginning to be used for this complication. DOACs are strong alternatives for warfarin because of their efficacy and safety even though there is no randomized controlled trial that proves the effect of DOACs against LVT. In this article, we gather the case reports of DOACs against left ventricular thrombi in various conditions.


Assuntos
Anticoagulantes/uso terapêutico , Ventrículos do Coração/patologia , Trombose/tratamento farmacológico , Administração Oral , Humanos , Infarto do Miocárdio/complicações , Trombose/etiologia , Resultado do Tratamento
6.
J Cardiothorac Surg ; 14(1): 55, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30866986

RESUMO

BACKGROUND: A newborn was diagnosed by echocardiogram with an asymptomatic cardiac mass in the right ventricle after a systolic cardiac murmur was detected at birth. CASE PRESENTATION: Nine days after birth, the newborn presented with three syncopal episodes and oxygen desaturation which required resuscitation. The mass induced a complete right ventricular outflow tract obstruction. The presence of a patent foramen oval and a patent ductus arteriosus explained the absence of symptoms at birth. Surgery was rapidly considered since the situation was life threatening. The tumor was successfully resected. The mass was a mature teratoma confirmed by microscopic examination, illustrated by pictures and video. CONCLUSIONS: This case was unique because of the absence of symptoms in the first 9 days of the newborn's life even though symptoms should have mounted due to the obstruction postpartum. The delay was correlated to the closure of the patent ductus arteriosus. It is recommended that newborns with any cardiac mass be followed up regularly due to hemodynamic changes at birth.


Assuntos
Neoplasias Cardíacas/diagnóstico , Ventrículos do Coração/patologia , Teratoma/diagnóstico , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia/métodos , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/cirurgia , Hemodinâmica , Humanos , Recém-Nascido , Teratoma/complicações , Teratoma/cirurgia
9.
Int J Cardiovasc Imaging ; 35(7): 1347-1355, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30838504

RESUMO

Myocardial crypts can be recognized in patients with hypertrophic cardiomyopathy (HCM) using magnetic resonance imaging, but similar studies using computed tomography (CT) are sparse. The aim of the present study was to evaluate the prevalence and morphology of myocardial crypts in patients with HCM, arterial hypertension, and aortic valve stenosis using contrast-enhanced CT. We also investigated the added value of a finding of myocardial crypts on CT scan to the diagnosis of HCM. The study cohort included 73 patients with HCM, 100 patients with arterial hypertension, 120 patients with aortic valve stenosis, and 100 subjects without cardiovascular disease (normal control group). All underwent evaluation for the presence and dimensions of myocardial crypts using 256-slice CT. Crypts were identified in 18 patients (24.7%) with HCM, 7 patients (7%) with hypertension, 8 patients (6.7%) with aortic valve stenosis, and 4 (4%) normal subjects (P < 0.001). Values of crypt length, width, area, and penetration into myocardium were highest in the HCM group. Crypt area differentiated patients with HCM from patients with arterial hypertension and aortic valve stenosis, and from normal control subjects. Crypt area was an accurate predictor of HCM, with an area under the receiver-operator characteristic curve of 0.88 (95% CI 0.80-0.96). Myocardial crypts identified by CT are more prevalent and larger in area in HCM than in arterial hypertension and aortic valve stenosis. Crypt area could potentially help to improve the diagnosis of HCM by CT beyond the assessment of left ventricular thickness or mass.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Ventrículos do Coração/diagnóstico por imagem , Hipertensão/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Miocárdio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/patologia , Técnicas de Imagem de Sincronização Cardíaca , Cardiomiopatia Hipertrófica/epidemiologia , Cardiomiopatia Hipertrófica/patologia , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Ventrículos do Coração/patologia , Humanos , Hipertensão/epidemiologia , Hipertensão/patologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Estudos Retrospectivos
11.
Toxicol Pathol ; 47(3): 311-328, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30727858

RESUMO

Cardiac electrophysiology utilizes nonimplantable, catheter-based devices for diagnosis and treatment of arrhythmias as well as electroanatomical mapping of cardiac chambers. Gross pathology and histopathological assessments in preclinical studies play critical roles in determining the safety and efficacy of cardiac ablation systems used to treat tachyarrhythmias. The pathologist must assess ablation sites, adjacent structures and organs, and downstream organs to characterize the effects of the ablation treatment and determine whether adverse local reactions, collateral injury, or downstream thromboembolism are present. Histopathological assessment serves as an adjunct to electroanatomical data in determining efficacy in preclinical studies. Histopathology is the standard in definitively demonstrating transmurality of ablation lesions, which is necessary for complete conduction block, as well as showing the linear or circumferential distribution of a contiguous, transmural ablation lesion necessary for electroanatomical isolation of entire target structures such as pulmonary veins and the cavotricuspid isthmus, which are involved in propagating certain arrhythmias. This article will detail gross and histological methods for the pathology assessment of preclinical studies evaluating the safety and/or efficacy of cardiac ablation catheter systems as well as discuss correlation of pathology data with other supporting evidence for safety and efficacy such as acute, electroanatomical data.


Assuntos
Cateteres Cardíacos/normas , Ablação por Cateter/instrumentação , Criocirurgia/instrumentação , Segurança de Equipamentos , Átrios do Coração/patologia , Ventrículos do Coração/patologia , Animais , Cateteres Cardíacos/efeitos adversos , Átrios do Coração/fisiopatologia , Átrios do Coração/cirurgia , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Taquicardia/cirurgia
12.
Exp Mol Med ; 51(2): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30765687

RESUMO

The lifetime risk of developing heart failure is approximately 20%, and survival rates remain poor. Myocardial mitochondrial function has been suggested to play a pivotal role in heart failure pathophysiology. Human studies on ex vivo mitochondrial function have mostly been limited to atrial tissue obtained during open heart surgery and have provided contradictory results. This study aimed at measuring myocardial mitochondrial function in transcatheter ventricular endomyocardial biopsies and assessing the relationship between oxidative capacity and heart function. We enrolled 40 heart failure patients undergoing ventricular assist device surgery or heart transplantation (34 males, age 57 ± 11 years, body mass index 26.6 ± 4.8 kg/m2) and 29 heart transplant recipients of comparable age and body mass index with normal left ventricular function undergoing surveillance biopsies (23 males, 57 ± 12 years, body mass index 26.2 ± 4.1 kg/m2). High-resolution respirometry was established in the myocardium to measure oxidative capacity ex vivo. The mitochondrial oxidative capacity was 90% higher in ventricular compared to atrial tissues (n = 11, p < 0.01) of explanted hearts. Respiration rates were comparable in ventricular samples of heart failure patients obtained during open heart surgery by standard tissue preparation or ex vivo endomyocardial biopsy (r = 0.9988, p < 0.0001, n = 8), and the mitochondrial oxidative capacity in samples from these patients remained stable for 8 h when stored in either of two common preservation buffers. The oxidative capacity was 44% lower in heart failure than in transplant recipients (67 ± 3 vs. 97 ± 5 pmol/[s mg], p < 0.0001) and correlated positively with heart function (r = 0.49, p < 0.01). High-resolution respirometry of ventricular tissue is feasible in transcatheter biopsies, facilitating clinical studies on myocardial mitochondrial function in patients not undergoing heart surgery.


Assuntos
Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Ventrículos do Coração/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo , Idoso , Biomarcadores , Biópsia , Respiração Celular , Comorbidade , Expressão Gênica , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Peróxido de Hidrogênio/metabolismo , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/metabolismo , Miocárdio/patologia , Oxirredução
13.
Med Phys ; 46(4): 1740-1751, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734937

RESUMO

PURPOSE: Accurate three-dimensional (3D) segmentation of myocardial replacement fibrosis (i.e., scar) is emerging as a potentially valuable tool for risk stratification and procedural planning in patients with ischemic cardiomyopathy. The main purpose of this study was to develop a semiautomated method using a 3D convolutional neural network (CNN)-based for the segmentation of left ventricle (LV) myocardial scar from 3D late gadolinium enhancement magnetic resonance (LGE-MR) images. METHODS: Our proposed CNN is built upon several convolutional and pooling layers aimed at choosing appropriate features from LGE-MR images to distinguish between myocardial scar and healthy tissues of the left ventricle. In contrast to previous methods that consider image intensity as the sole feature, CNN-based algorithms have the potential to improve the accuracy of scar segmentation through the creation of unconventional features that separate scar from normal myocardium in the feature space. The first step of our pipeline was to manually delineate the left ventricular myocardium, which was used as the region of interest for scar segmentation. Our developed algorithm was trained using 265,220 volume patches extracted from ten 3D LGE-MR images, then was validated on 450,454 patches from a testing dataset of 24 3D LGE-MR images, all obtained from patients with chronic myocardial infarction. We evaluated our method in the context of several alternative methods by comparing algorithm-generated segmentations to manual delineations performed by experts. RESULTS: Our CNN-based method reported an average Dice similarity coefficient (DSC) and Jaccard Index (JI) of 93.63% ± 2.6% and 88.13% ± 4.70%. In comparison to several previous methods, including K-nearest neighbor (KNN), hierarchical max flow (HMF), full width at half maximum (FWHM), and signal threshold to reference mean (STRM), the developed algorithm reported significantly higher accuracy for DSC with a P-value less than 0.0001. CONCLUSIONS: Our experimental results demonstrated that our CNN-based proposed method yielded the highest accuracy of all contemporary LV myocardial scar segmentation methodologies, inclusive of the most widely used signal intensity-based methods, such as FWHM and STRM. To our knowledge, this is the first description of LV myocardial scar tissue segmentation from 3D LGE-MR images using a CNN-based method.


Assuntos
Cardiomiopatias/patologia , Ventrículos do Coração/patologia , Aumento da Imagem , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Algoritmos , Estudos de Casos e Controles , Meios de Contraste , Feminino , Gadolínio , Humanos , Aumento da Imagem/métodos , Imagem Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Redes Neurais (Computação)
14.
Int J Cardiovasc Imaging ; 35(7): 1309-1318, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30790116

RESUMO

Hypertrophic cardiomyopathy (HCM) is associated with increased left ventricular (LV) mass, decreased myocardial strain, and the presence of LV fibrosis and scar. The relationship between LV scar and fibrosis with left atrial (LA) fibrosis in the setting of HCM has not been examined. The purpose of this study is to demonstrate a correlation between the degree of LA fibrosis and LV parameters in subjects with HCM. Twenty-eight subjects with HCM were imaged on a 1.5T MRI scanner with cine, LV and LA late gadolinium enhancement (LGE) sequences. LA LGE and LA measurements were correlated with LV measurements of volumes, mass, strain, and LGE. Other clinical conditions and medication usage were also examined and evaluated for correlation with LA and LV parameters. LV LGE was identified in 24 (86%) of the cases and LA LGE was identified in all of the cases. Extent of LA fibrosis significantly correlated with percent LV LGE (r = 0.64, p = 0.001), but not with indexed LV mass or maximum wall thickness. Extent of LA fibrosis also moderately correlated with decreased LV global strain (radial, r = - 0.50, p = 0.013; circumferential, r = 0.47, p = 0.02; longitudinal, r = 0.52, p = 0.013). Increased LA systolic volume correlated moderately with LV end diastolic volume (r = 0.50, p = 0.006). Patients on therapy with Renin-Angiotensin-Aldosterone System (RAAS) Inhibition had significantly less LA LGE compared to those without (18.6% vs 10.8%, p = 0.023). LA fibrosis, as measured by LGE, is prevalent in HCM and is correlated with LV LGE. The correlation between LA and LV LGE might suggest either that LA fibrosis is a consequence of LV remodeling, or that LA and LV fibrosis are both manifestations of the same cardiomyopathic process. Further study is warranted to determine the causality of LA scar in this population.


Assuntos
Função do Átrio Esquerdo , Remodelamento Atrial , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Função do Átrio Esquerdo/efeitos dos fármacos , Remodelamento Atrial/efeitos dos fármacos , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Meios de Contraste/administração & dosagem , Feminino , Fibrose , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/patologia , Átrios do Coração/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos/administração & dosagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
15.
Int Heart J ; 60(2): 477-481, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30745532

RESUMO

This case report demonstrates a pair of monozygotic twins with hypertrophic cardiomyopathy (HCM) carrying the same pathogenic mutation of MYH7 (p.G768R; c.2302G>A), detected by whole exome and Sanger genetic sequencing methods. On multi-modality imaging, they were reported to have similar, but not identical, morphologic expression. Particularly, the clinical presentation and tissue characteristics were not the same. Late gadolinium enhancement (LGE) and T1 mapping of cardiac magnetic resonance showed different extents of myocardial fibrotic characteristics in the twins (twin A: 16.3% LGE and 32.6% extracellular volume [ECV] of the whole left ventricle; twin B: 5.4% LGE and 28.1% ECV of the whole left ventricle). This extraordinary case of HCM provides evidence on the complex pathophysiological mechanisms of HCM and suggests the likely impact of epigenetics and environmental factors on HCM phenotype.


Assuntos
Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica Familiar , Ecocardiografia/métodos , Eletrocardiografia/métodos , Ventrículos do Coração , Imagem Cinética por Ressonância Magnética/métodos , Cadeias Pesadas de Miosina/genética , Cardiomiopatia Hipertrófica Familiar/diagnóstico , Cardiomiopatia Hipertrófica Familiar/genética , Cardiomiopatia Hipertrófica Familiar/fisiopatologia , Meios de Contraste/farmacologia , Gerenciamento Clínico , Epigênese Genética , Feminino , Gadolínio/farmacologia , Interação Gene-Ambiente , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Mutação , Tamanho do Órgão , Gêmeos Monozigóticos
16.
Int J Nanomedicine ; 14: 851-863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774338

RESUMO

Purpose: This study was carried out to investigate the effects of a triptolide (TP) nanosuspension and methotrexate (MTX) nanosuspension on left ventricular remodeling and cardiac function for autoimmune myocarditis (EAM) in rats. The regulating effects on inflammatory cytokines in the peripheral serum and related mechanisms are also discussed. Methods: First, TP and MTX were prepared as a nanosuspension, and the EAM model was successfully established in rats with cardiac myosin. Then, the effect of TP and MTX suspensions was tested in an EAM model. Results: Results revealed that both TP and MTX suspensions could reduce the degree of myocardial fibrosis and delay the remodeling process of the left ventricle which could further improve cardiac function. Finally, it was found that inflammatory cytokines in the peripheral serum were regulated by the nonspecific immune system and the inhibition of nuclear factor-κB signaling might have partly occurred due to this mechanism. Conclusion: In summary, this study provided a complete foundation for EAM therapy of profound clinical relevance.


Assuntos
Diterpenos/uso terapêutico , Metotrexato/uso terapêutico , Miocardite/tratamento farmacológico , Miocardite/fisiopatologia , Nanopartículas/química , Fenantrenos/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Citocinas/sangue , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Testes de Função Cardíaca , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Masculino , Metotrexato/farmacologia , Miocardite/sangue , Miocardite/diagnóstico por imagem , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Fenantrenos/farmacologia , Fosforilação/efeitos dos fármacos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Suspensões
17.
Molecules ; 24(1)2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30621310

RESUMO

Sustained pacemaker function is a challenge in biological pacemaker engineering. Human cardiomyocyte progenitor cells (CMPCs) have exhibited extended survival in the heart after transplantation. We studied whether lentivirally transduced CMPCs that express the pacemaker current If (encoded by HCN4) can be used as functional gene delivery vehicle in biological pacing. Human CMPCs were isolated from fetal hearts using magnetic beads coated with Sca-1 antibody, cultured in nondifferentiating conditions, and transduced with a green fluorescent protein (GFP)- or HCN4-GFP-expressing lentivirus. A patch-clamp analysis showed a large hyperpolarization-activated, time-dependent inward current (-20 pA/pF at -140 mV, n = 14) with properties typical of If in HCN4-GFP-expressing CMPCs. Gap-junctional coupling between CMPCs and neonatal rat ventricular myocytes (NRVMs) was demonstrated by efficient dye transfer and changes in spontaneous beating activity. In organ explant cultures, the number of preparations showing spontaneous beating activity increased from 6.3% in CMPC/GFP-injected preparations to 68.2% in CMPC/HCN4-GFP-injected preparations (P < 0.05). Furthermore, in CMPC/HCN4-GFP-injected preparations, isoproterenol induced a significant reduction in cycle lengths from 648 ± 169 to 392 ± 71 ms (P < 0.05). In sum, CMPCs expressing HCN4-GFP functionally couple to NRVMs and induce physiologically controlled pacemaker activity and may therefore provide an attractive delivery platform for sustained pacemaker function.


Assuntos
Técnicas de Transferência de Genes , Ventrículos do Coração/transplante , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Proteínas Musculares/genética , Miócitos Cardíacos/transplante , Canais de Potássio/genética , Células-Tronco/citologia , Animais , Terapia Genética/métodos , Proteínas de Fluorescência Verde/química , Ventrículos do Coração/patologia , Humanos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/uso terapêutico , Proteínas Musculares/uso terapêutico , Técnicas de Patch-Clamp , Canais de Potássio/uso terapêutico , Ratos , Transplante de Células-Tronco
18.
Medicine (Baltimore) ; 98(4): e14257, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30681621

RESUMO

This study aimed to evaluate left ventricular deformation in relation to the geometric pattern in hypertensive patients with normal left ventricular ejection fraction using speckle tracking echocardiography (STE).Transthoracic echocardiography was performed in 80 hypertensive patients and 50 age- and gender-matched normotensive subjects. Left ventricular geometric pattern was defined according to left ventricular mass index and relative wall thickness as normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, respectively. Quantitative measurements of longitudinal, circumferential, and radial strain were performed for endocardial, middle, and epicardial layers of the left ventricular wall at each segment.The longitudinal strain in hypertension was lower for all 3 layers in concentric (n = 20) and eccentric hypertrophy (n = 20) than normotensive subjects (n = 50, P < .01). It was also significantly lower for the endocardial layer in concentric remodeling (n = 20, P = .04 vs normotensive subjects). The circumferential strain in hypertension was higher in normal geometry or concentric remodeling, lower in concentric hypertrophy, and at similar level in eccentric hypertrophy, in comparison with normotensive subjects. The difference from normotensive subjects was statistically significant for the endocardial and middle layers in normal geometry (P < .03), for the endocardial layer in concentric remodeling (P < .02), and for the middle and epicardial layers in concentric hypertrophy (P≤.001). The radial strain and twist did not differ between normotensive and hypertensive subjects (P > .08).Left ventricular deformation in hypertension occurs with various geometric patterns disproportionately in the endocardial, middle and epicardial layers and differently in the longitudinal and circumferential orientations.


Assuntos
Ecocardiografia , Ventrículos do Coração/patologia , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/patologia , Adulto , Estudos de Casos e Controles , Endocárdio/diagnóstico por imagem , Endocárdio/patologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda
19.
Forensic Sci Int ; 296: 22-27, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30641441

RESUMO

BACKGROUND: Measurement of heart weight is important when investigating cause of death, but there is presently no satisfactory method of heart weight estimation by postmortem computed tomography (PMCT). METHOD: We investigated 33 consecutive cases that underwent both PMCT and autopsy between February 2008 and June 2014. Heart and left ventricular (LV) weights were calculated by PMCT morphometry. We used a simple method to estimate LV weight: We assumed that LV was an ellipsoid and multiplied its volume on PMCT with myocardial specific gravity. We then compared the various heart and LV weights using linear regression. The calculated and estimated LV weights on PMCT were also compared. RESULTS: It was not possible to predict heart weight at autopsy from PMCT (R2 = 0.53). However, heart weight at autopsy could be accurately predicted from LV weight calculated by PMCT (R2 = 0.77). In addition, there was a strong correlation between the estimated and calculated LV weights by PMCT (R2 = 0.92). Heart weight at autopsy could also be accurately predicted using the PMCT-estimated LV weight (R2 = 0.72). CONCLUSION: Heart weight at autopsy could be accurately predicted using a simple method in which LV volume was assumed to be an ellipsoid on PMCT.


Assuntos
Coração/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Miocárdio/patologia , Tamanho do Órgão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autopsia , Criança , Feminino , Patologia Legal , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
20.
Forensic Sci Med Pathol ; 15(2): 272-275, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30649692

RESUMO

Cardiac injury following blunt chest trauma is common in motor vehicle accidents due to a crush or blast injury. Severe cardiac trauma is associated with a very high mortality. If a cardiac injury develops several weeks after non-penetrating chest trauma, establishing a causal link between the traumatic event and the cardiac injury becomes complicated. This article reports a case of fatal delayed hemopericardium and hemothorax following a motor vehicle accident including blunt chest trauma 34 days prior to death. The cardiac injury was caused by displacement of a sharp irregular fragment of one of the decedents fractured ribs and the primary defect was sealed by blood clots. Subsequent bleeding occurred when the thrombus was displaced. Since the incidence of blunt high-energy chest injuries is relatively high, heart and large vessel injuries must be taken into account and a comprehensive examination needs to be done in order to prevent the delayed development of fatal complications.


Assuntos
Hemotórax/etiologia , Derrame Pericárdico/etiologia , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Feminino , Ventrículos do Coração/lesões , Ventrículos do Coração/patologia , Hemotórax/patologia , Humanos , Pessoa de Meia-Idade , Pedestres , Derrame Pericárdico/patologia , Fraturas das Costelas/complicações , Fraturas das Costelas/patologia , Choque Hemorrágico/etiologia , Trombose/patologia , Fatores de Tempo
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