Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.847
Filtrar
1.
Medicine (Baltimore) ; 100(27): e25915, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232164

RESUMO

ABSTRACT: Early right ventricular dysfunction in patients with non-advanced idiopathic pulmonary fibrosis (IPF) has not been fully elucidated. Thus, we aimed to assess right ventricular functions in IPF patients and controls by speckle-tracking strain echocardiography at rest and peak exercise.We screened 116 IPF patients from February to August 2019 to include 20 patients with no history of oxygen therapy, peripheral saturation levels ≥92% at rest, Gender-Age-Physiology Index score ≤5, and modified Medical Research Council score ≤3. Additionally, we enrolled 10 matched controls. Transthoracic echocardiography images were acquired at rest and during a cardiopulmonary exercise test. We analyzed 2-dimensional echocardiographic parameters and right ventricular function using the global longitudinal strain assessed by the 2-dimensional speckle-tracking technique.In the control group, we found normal values of right ventricle longitudinal strain (RVLS) at rest and at peak exercise, the latter being much more negative (-23.6 ±â€Š2.2% and -26.8 ±â€Š3.1%, respectively; P < .001). By contrast, RVLS values in the IPF group increased from -21.1 ±â€Š3.8% at rest to -17.0 ±â€Š4.5% at peak exercise (P < .001). The exercise revealed a difference between the 2 groups as the mean RVLS values moved during peak exercise in opposite directions. Patients with IPF got worse, whereas control patients presented improved right ventricular contractility.Right ventricular dysfunction was unveiled by speckle-tracking echocardiography during exercise in non-advanced IPF patients. We suggest that this reflects an inadequate right ventricular-arterial coupling decreasing the right ventricular longitudinal contraction during exercise in these patients. This parameter may be useful as an early index of suspected pulmonary hypertension.


Assuntos
Terapia por Exercício/métodos , Exercício Físico/fisiologia , Ventrículos do Coração/fisiopatologia , Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar Idiopática/fisiopatologia , Contração Miocárdica/fisiologia , Função Ventricular Direita/fisiologia , Idoso , Estudos Transversais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Fibrose Pulmonar Idiopática/complicações , Masculino
2.
Methods Mol Biol ; 2277: 405-421, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34080165

RESUMO

The more recent studies of human pathologies have essentially revealed the complexity of the interactions involved at the different levels of integration in organ physiology. Integrated organ thus reveals functional properties not predictable by underlying molecular events. It is therefore obvious that current fine molecular analyses of pathologies should be fruitfully combined with integrative approaches of whole organ function. It follows that an important issue in the comprehension of the link between molecular events in pathologies and whole organ function/dysfunction is the development of new experimental strategies aimed at the study of the integrated organ physiology. Cardiovascular diseases are a good example as heart submitted to ischemic conditions has to cope both with a decreased supply of nutrients and oxygen, and the necessary increased activity required to sustain whole body-including the heart itself-oxygenation.By combining the principles of control analysis with noninvasive 31P NMR measurement of the energetic intermediates and simultaneous measurement of heart contractile activity, we developed MoCA (for Modular Control and regulation Analysis), an integrative approach designed to study in situ control and regulation of cardiac energetics during contraction in intact beating perfused isolated heart (Diolez et al., Am J Physiol Regul Integr Comp Physiol 293(1):R13-R19, 2007). Because it gives real access to integrated organ function, MoCA brings out a new type of information-the "elasticities," referring to integrated internal responses to metabolic changes-that may be a key to the understanding of the processes involved in pathologies. MoCA can potentially be used not only to detect the origin of the defects associated with the pathology, but also to provide the quantitative description of the routes by which these defects-or also drugs-modulate global heart function, therefore opening therapeutic perspectives. This review presents selected examples of the applications to isolated intact beating heart that evidence different modes of energetic regulation of cardiac contraction. We also discuss the clinical application by using noninvasive 31P cardiac energetics examination under clinical conditions for detection of heart pathologies.


Assuntos
Metabolismo Energético , Espectroscopia de Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Animais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Metabolismo Energético/efeitos dos fármacos , Epinefrina/metabolismo , Cobaias , Coração/efeitos dos fármacos , Homeostase , Humanos , Masculino , Mitocôndrias Cardíacas/metabolismo , Miofibrilas/metabolismo , Técnicas de Cultura de Órgãos/métodos , Ratos , Simendana/farmacologia
3.
Nat Commun ; 12(1): 2942, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011988

RESUMO

The association between reduced myofilament force-generating capacity (Fmax) and heart failure (HF) is clear, however the underlying molecular mechanisms are poorly understood. Here, we show impaired Fmax arises from reduced BAG3-mediated sarcomere turnover. Myofilament BAG3 expression decreases in human HF and positively correlates with Fmax. We confirm this relationship using BAG3 haploinsufficient mice, which display reduced Fmax and increased myofilament ubiquitination, suggesting impaired protein turnover. We show cardiac BAG3 operates via chaperone-assisted selective autophagy (CASA), conserved from skeletal muscle, and confirm sarcomeric CASA complex localization is BAG3/proteotoxic stress-dependent. Using mass spectrometry, we characterize the myofilament CASA interactome in the human heart and identify eight clients of BAG3-mediated turnover. To determine if increasing BAG3 expression in HF can restore sarcomere proteostasis/Fmax, HF mice were treated with rAAV9-BAG3. Gene therapy fully rescued Fmax and CASA protein turnover after four weeks. Our findings indicate BAG3-mediated sarcomere turnover is fundamental for myofilament functional maintenance.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Insuficiência Cardíaca/fisiopatologia , Miócitos Cardíacos/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Animais , Proteínas Reguladoras de Apoptose/deficiência , Proteínas Reguladoras de Apoptose/genética , Modelos Animais de Doenças , Feminino , Terapia Genética , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas Musculares/metabolismo , Contração Miocárdica/genética , Contração Miocárdica/fisiologia , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Sarcômeros/metabolismo
4.
Pediatr Cardiol ; 42(6): 1341-1349, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33891133

RESUMO

Myocardial strain offers new insights into ventricular performance, There are software packages from several different companies used to ascertain this, and little data is available in patients with single right ventricle (sRV) physiology. We aimed to compare the analysis of two strain software applications using a cohort of patients with sRV for both inter-vendor and inter-observer variability. Echocardiograms from 85 patients with sRV (122 separate studies) were prospectively evaluated. All had Glenn and/or Fontan palliation. Longitudinal 4-chamber (4LS), inflow/outflow (IO), circumferential, and radial strain were assessed using Velocity Vector Imaging (VVI, Seimens, Munich) and Automated Functional Imaging (AFI, General Electric, Boston) software. In a subset of 45 patients (61 separate studies), strain measurements were obtained by two sonographers so a paired "inter-observer" analysis could be performed. A moderate correlation between measurements made by the two systems was observed. Circumferential strain assessment had the highest R value (0.77) with all others having R values < 0.6. Both software packages showed modest inter-observer reproducibility for longitudinal and circumferential strain. VVI intraclass correlation coefficients (ICC) for 4LS and average circumferential strain (ACS) were 0.6 and 0.58, compared to 0.68 and 0.59 for AFI. Other than radial strain and VVI IO inferior strain, mean strain differences between AFI and VVI were ≤ 1%. Inter-observer variability is modest, however, mean differences are minimal suggesting reasonable clinical reliability. Inter-vendor variability is greater and not as clinically reliable. In patients with sRV, serial assessments with strain should be performed using the same software.


Assuntos
Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Contração Miocárdica/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Técnica de Fontan/métodos , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Humanos , Lactente , Masculino , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
6.
Undersea Hyperb Med ; 48(1): 73-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33648036

RESUMO

Venous gas emboli (VGE) are often quantified as a marker of decompression stress on echocardiograms. Bubble-counting has been proposed as an easy to learn method, but remains time-consuming, rendering large dataset analysis impractical. Computer automation of VGE counting following this method has therefore been suggested as a means to eliminate rater bias and save time. A necessary step for this automation relies on the selection of a frame during late ventricular diastole (LVD) for each cardiac cycle of the recording. Since electrocardiograms (ECG) are not always recorded in field experiments, here we propose a fully automated method for LVD frame selection based on regional intensity minimization. The algorithm is tested on 20 previously acquired echocardiography recordings (from the original bubble-counting publication), half of which were acquired at rest (Rest) and the other half after leg flexions (Flex). From the 7,140 frames analyzed, sensitivity was found to be 0.913 [95% CI: 0.875-0.940] and specificity 0.997 [95% CI: 0.996-0.998]. The method's performance is also compared to that of random chance selection and found to perform significantly better (p≺0.0001). No trend in algorithm performance was found with respect to VGE counts, and no significant difference was found between Flex and Rest (p>0.05). In conclusion, full automation of LVD frame selection for the purpose of bubble counting in post-dive echocardiography has been established with excellent accuracy, although we caution that high quality acquisitions remain paramount in retaining high reliability.


Assuntos
Algoritmos , Diagnóstico por Computador/métodos , Mergulho/fisiologia , Ecocardiografia/métodos , Embolia Aérea/diagnóstico por imagem , Função Ventricular/fisiologia , Doença da Descompressão/diagnóstico por imagem , Diagnóstico por Computador/estatística & dados numéricos , Diástole/fisiologia , Ecocardiografia/estatística & dados numéricos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Contração Miocárdica/fisiologia , Sensibilidade e Especificidade
7.
Biomed Res Int ; 2021: 8492705, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553431

RESUMO

Myocardial strain is a well-validated parameter for evaluating myocardial contraction. Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel method for the quantitative measurements of myocardial strain from routine cine acquisitions. In this study, we investigated the influence of temporal resolution on tracking accuracy of CMR-FT and the intraobserver, interobserver, and interstudy reproducibilities for biventricular strain analysis in mice from self-gated CMR at 11.7 T. 12 constitutive nexilin knockout (Nexn-KO) mice, heterozygous (Het, N = 6) and wild-type (WT, N = 6), were measured with a well-established self-gating sequence twice within two weeks. CMR-FT measures of biventricular global and segmental strain parameters were derived. Interstudy, intraobserver, and interobserver reproducibilities were investigated. For the assessment of the impact of the temporal resolution for the outcome in CMR-FT, highly oversampled semi-4 chamber and midventricular short-axis data were acquired and reconstructed with 10 to 80 phases per cardiac cycle. A generally reduced biventricular myocardial strain was observed in Nexn-KO Het mice. Excellent intraobserver and interobserver reproducibility was achieved in all global strains (ICC range from 0.76 to 0.99), where global right ventricle circumferential strain (RCSSAX) showed an only good interobserver reproducibility (ICC 0.65, 0.11-0.89). For interstudy reproducibility, left ventricle longitudinal strain (LLSLAX) was the most reproducible measure of strain (ICC 0.90, 0.71-0.97). The left ventricle radial strain (LRSSAX) (ICC 0.50, 0.10-0.83) showed fair reproducibility and RCSSAX (ICC 0.36, 0.14-0.74) showed only poor reproducibility. In general, compared with global strains, the segmental strains showed relatively lower reproducibility. A minimal temporal resolution of 20 phases per cardiac cycle appeared sufficient for CMR-FT strain analysis. The analysis of myocardial strain from high-resolution self-gated cine images by CMR-FT provides a highly reproducible method for assessing myocardial contraction in small rodent animals. Especially, global LV longitudinal and circumferential strain revealed excellent reproducibility of intra- and interobserver and interstudy measurements.


Assuntos
Ventrículos do Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Proteínas dos Microfilamentos/genética , Contração Miocárdica/fisiologia , Animais , Feminino , Coração/diagnóstico por imagem , Frequência Cardíaca , Modelos Lineares , Masculino , Camundongos Knockout , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Função Ventricular/fisiologia
8.
Int J Mol Sci ; 22(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466228

RESUMO

Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia worldwide and is associated with ischemic stroke, heart failure, and substantial morbidity and mortality. Unfortunately, current AF therapy is only moderately effective and does not prevent AF progression from recurrent intermittent episodes (paroxysmal) to persistent and finally permanent AF. It has been recognized that AF persistence is related to the presence of electropathology. Electropathology is defined as structural damage, including degradation of sarcomere structures, in the atrial tissue which, in turn, impairs electrical conduction and subsequently the contractile function of atrial cardiomyocytes. Recent research findings indicate that derailed proteostasis underlies structural damage and, consequently, electrical conduction impairment. A healthy proteostasis is of vital importance for proper function of cells, including cardiomyocytes. Cells respond to a loss of proteostatic control by inducing a heat shock response (HSR), which results in heat shock protein (HSP) expression. Emerging clinical evidence indicates that AF-induced proteostasis derailment is rooted in exhaustion of HSPs. Cardiomyocytes lose defense against structural damage-inducing pathways, which drives progression of AF and induction of HSP expression. In particular, small HSPB1 conserves sarcomere structures by preventing their degradation by proteases, and overexpression of HSPB1 accelerates recovery from structural damage in experimental AF model systems. In this review, we provide an overview of the mechanisms of action of HSPs in preventing AF and discuss the therapeutic potential of HSP-inducing compounds in clinical AF, as well as the potential of HSPs as biomarkers to discriminate between the various stages of AF and recurrence of AF after treatment.


Assuntos
Fibrilação Atrial/metabolismo , Proteínas de Choque Térmico/metabolismo , Animais , Átrios do Coração/metabolismo , Resposta ao Choque Térmico/fisiologia , Humanos , Contração Miocárdica/fisiologia , Miócitos Cardíacos/metabolismo , Proteostase/fisiologia
9.
Circ Arrhythm Electrophysiol ; 14(2): e009291, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33417472

RESUMO

BACKGROUND: Arrhythmias and heart failure are common cardiac complications leading to substantial morbidity and mortality in patients with hemochromatosis, yet mechanistic insights remain incomplete. We investigated the effects of iron (Fe) on electrophysiological properties and intracellular Ca2+ (Ca2+i) handling in mouse left ventricular cardiomyocytes. METHODS: Cardiomyocytes were isolated from the left ventricle of mouse hearts and were superfused with Fe3+/8-hydroxyquinoline complex (5-100 µM). Membrane potential and ionic currents including TRPC (transient receptor potential canonical) were recorded using the patch-clamp technique. Ca2+i was evaluated by using Fluo-4. Cell contraction was measured with a video-based edge detection system. The role of TRPCs in the genesis of arrhythmias was also investigated by using a mathematical model of a mouse ventricular myocyte with the incorporation of the TRPC component. RESULTS: We observed prolongation of the action potential duration and induction of early and delayed afterdepolarizations in myocytes superfused with 15 µmol/L Fe3+/8-hydroxyquinoline complex. Iron treatment decreased the peak amplitude of the L-type Ca2+ current and total K+ current, altered Ca2+i dynamics, and decreased cell contractility. During the final phase of Fe treatment, sustained Ca2+i waves and repolarization failure occurred and ventricular cells became unexcitable. Gadolinium abolished Ca2+i waves and restored the resting membrane potential to the normal range. The involvement of TRPC activation was confirmed by TRPC channel current recordings in the absence or presence of functional TRPC channel antibodies. Computer modeling captured the same action potential and Ca2+i dynamics and provided additional mechanistic insights. CONCLUSIONS: We conclude that iron overload induces cardiac dysfunction that is associated with TRPC channel activation and alterations in membrane potential and Ca2+i dynamics.


Assuntos
Potenciais de Ação/fisiologia , Arritmias Cardíacas/metabolismo , Cálcio/metabolismo , Sobrecarga de Ferro/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Arritmias Cardíacas/patologia , Arritmias Cardíacas/fisiopatologia , Sinalização do Cálcio , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos , Sobrecarga de Ferro/patologia , Sobrecarga de Ferro/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Miocárdica/fisiologia , Miócitos Cardíacos/patologia , Técnicas de Patch-Clamp
10.
Phytomedicine ; 83: 153468, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33513559

RESUMO

BACKGROUND: Aconitine-induced cardiotoxicity limits the clinical treatment of cardiotonic, cancers and immune-related diseases. Ginsenoside Rb1 (Rb1) is an active ingredient of traditional Chinese medicine with cardioprotective effect. PURPOSE: This study aims to study the mechanism of aconitine cardiotoxicity and the detoxification mechanism of Rb1. STUDY DESIGN: METHODS: The regulatory effect of Rb1 on aconitine was evaluated in vitro and in vivo by myocardial enzyme indicators, pathological analysis, CardioECR detection, calcium transient analysis, western blotting and immunohistochemistry. RESULTS: Rb1 (10, 20, 40 mg/kg) alleviated apoptotic myocardial damage caused by aconitine in rats. Furthermore, Rb1 (25, 50, 100 µM) restored the contractile function and field potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by regulating calcium channels and reduced myocardial cell damage by inhibiting the calcium transients of adult rat ventricular myocytes (ARVMs). Rb1 significantly reduced calcium levels in hiPSC-CMs, directly indicating that aconitine-induced calcium overload was alleviated by Rb1. Further, aconitine caused calcium overload by changing the expression of calcium pathway proteins, while Rb1 effectively restored calcium homeostasis. In addition, Rb1 also had a cardioprotective role by inhibiting cell pyroptosis. These results suggested that the maintenance of calcium homeostasis helped to suppress the inflammatory response related to pyroptosis of the heart. CONCLUSION: Aconitine-induced cardiotoxicity can be alleviated by Rb1 via restoring calcium homeostasis and inhibiting apoptosis and pyroptosis.


Assuntos
Aconitina/efeitos adversos , Cálcio/metabolismo , Cardiotônicos/farmacologia , Cardiotoxicidade/tratamento farmacológico , Ginsenosídeos/farmacologia , Animais , Canais de Cálcio/metabolismo , Cardiotônicos/efeitos adversos , Cardiotoxicidade/etiologia , Humanos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Piroptose/efeitos dos fármacos , Ratos Sprague-Dawley
11.
Am Heart J ; 231: 45-55, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33098811

RESUMO

BACKGROUND: Few therapies improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF). If left bundle-branch block (LBBB) is associated with left ventricular dyssynchrony and impaired cardiac performance in HFpEF, cardiac resynchronization therapy could be a promising treatment. METHODS: We performed a cross-sectional analysis of selected patients with HFpEF (ejection fraction ≥50%) with and without LBBB (normal conduction, NC) and patients with HFrEF and LBBB who were suitable cardiac resynchronization therapy candidates to describe and contextualize the mechanical phenotype of LBBB in HFpEF. Systolic and diastolic isovolumic times, ejection time(ET), and diastolic filling time(DFT) were measured on spectral tissue Doppler echocardiographic images and indexed to the heart rate. Dyssynchrony pattern was assessed using speckle-tracked longitudinal strain patterns. Comparisons were performed using analysis of variance and χ2 test with posthoc pairwise comparisons as indicated. RESULTS: Eighty-two HFpEF (50 with NC, 32 with LBBB) and 149 HFrEF (all with LBBB) patients met criteria. Overall, 84.4% with HFpEF/LBBB and 91.3% with HFrEF/LBBB had demonstrable mechanical dyssynchrony compared to 0% with HFpEF/NC. Compared to HFpEF/NC, HFpEF/LBBB had significantly prolonged isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and total isovolumetric time and significantly shorter ET (all indexed). LBBB/HFrEF patients, compared to LBBB/HFpEF patients, had increased ICT and IRT with decreased DFT but similar ET. CONCLUSIONS: Patients with HFpEF and LBBB frequently have an LBBB dyssynchrony phenotype, prolonged ICT and IRT, and reduced ET compared to HFpEF patients with NC. The electromechanical dyssynchrony and disordered cardiac timing of HFpEF with LBBB are similar to HFrEF with LBBB.


Assuntos
Bloqueio de Ramo/complicações , Insuficiência Cardíaca/complicações , Contração Miocárdica , Volume Sistólico , Disfunção Ventricular Esquerda/complicações , Idoso , Análise de Variância , Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca , Distribuição de Qui-Quadrado , Estudos Transversais , Ecocardiografia , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Contração Miocárdica/fisiologia , Fenótipo , Estudos Retrospectivos , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia
12.
BJOG ; 128(2): 272-279, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32725766

RESUMO

OBJECTIVE: To determine whether cardiac functional and structural changes in fetuses of mothers with gestational diabetes mellitus (GDM) persist in the offspring beyond the neonatal period. DESIGN: Longitudinal study. SETTING: Fetal Medicine Unit in a UK teaching hospital. METHODS: 73 women with GDM and 73 women with uncomplicated pregnancy were recruited and fetal cardiac scans were performed at 35-36 weeks' gestation. Repeat echocardiogram was performed in their offspring during infancy. MAIN OUTCOME MEASURES: Fetal and infant cardiac functional and structural changes. RESULTS: Fetuses of mothers with GDM, compared with controls, had more globular right ventricles (sphericity index 0.7, interquartile range [IQR] 0.6/0.7 versus 0.6, IQR 0.5/0.6, P < 0.001) and reduced right global longitudinal systolic strain (-16.4, IQR -18.9/-15.3 versus -18.5, IQR -20.6/-16.8, P = 0.001) and left global longitudinal systolic strain (-20.1, IQR -22.5/-16.9 versus -21.3, IQR -23.5/-19.5), P = 0.021). In the GDM group, compared with controls, in infancy there was higher left ventricular E/e' (8.7, IQR 7.3/9.7 versus 7.9 IQR, 6.8/8.9 P = 0.011) and lower left ventricular global longitudinal systolic strain (-21.0, IQR -22.5/-19.4 versus -22.3, IQR -23.5/-20.7, P = 0.001) and tricuspid annular plane systolic excursion (13.8, IQR 12.7/16.1 versus 15.2, IQR 13.8/16.8, P = 0.003). These differences remained following multivariable analysis. CONCLUSION: Gestational diabetes mellitus is associated with alterations in fetal cardiac function and structure compared with controls and persistent cardiac changes in infancy. TWEETABLE ABSTRACT: Gestational diabetes mellitus, even when well controlled, is associated with fetal cardiac changes and these persist in infancy.


Assuntos
Diabetes Gestacional/diagnóstico por imagem , Diabetes Gestacional/fisiopatologia , Coração Fetal/diagnóstico por imagem , Coração Fetal/fisiopatologia , Contração Miocárdica/fisiologia , Função Ventricular/fisiologia , Fatores Etários , Estudos de Casos e Controles , Ecocardiografia , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Gravidez , Estudos Prospectivos , Reino Unido
13.
Heart Vessels ; 36(1): 92-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32632552

RESUMO

Diastolic intraventricular pressure difference (IVPD) reflects left ventricular (LV) diastolic function. The relative pressure imaging (RPI) enables the noninvasive quantification of IVPD based on vector flow mapping (VFM) and visualization of regional pressure distribution. LV dyssynchrony causes deterioration of cardiac performance. However, it remains unclear how IVPD is modulated by LV dyssynchrony. LV dyssynchrony was created in ten open-chest dogs by right ventricular (RV) pacing. The other ten dogs undergoing right atrial (RA) pacing set at the similar heart rate with RV pacing were used as controls. Echocardiographic images were acquired at baseline and during pacing simultaneously with LV pressure measurement by a micromanometer. Pressure difference (ΔP) was computed between the apex and the base of the LV inflow tract during a cardiac cycle by RPI and ΔP during isovolumic relaxation time (ΔPIRT), a parameter of diastolic suction, and that during early filling phase (ΔPE) were measured. During RV pacing, stroke volume (SV) and ΔPIRT decreased significantly, while ΔPE did not change compared to the baseline. During RA pacing, SV, ΔPIRT and ΔPE did not change significantly. ΔPIRT tended to correlate with -dP/dtmin and end-systolic volume, and significantly correlated with ejection fraction. IVPD during isovolumic relaxation time was decreased by LV dyssynchrony, while IVPD during early filling phase was not. A reduction of diastolic suction is observed in LV dyssynchrony and is significantly related to a decrease in SV.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Pressão Ventricular/fisiologia , Animais , Diástole , Modelos Animais de Doenças , Cães , Ecocardiografia , Feminino , Frequência Cardíaca/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico
15.
Expert Rev Med Devices ; 18(1): 15-21, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33287592

RESUMO

Introduction: Heart failure (HF) affects over 6 million Americans and approximately 650,000 new cases are diagnosed annually, with patients evenly split between HFrEF and HFpEF. Recent advances in therapy for these patients have been limited to pharmaceutical agents, with CRT remaining the most reliable device therapy option since its advent almost twenty years ago. In 2019, after almost two decades without the introduction of a new device therapy for the treatment of moderate HF, the FDA approved CCM® therapy, delivered by the Optimizer Smart device, for patients with NYHA Class III HF who are on guideline-directed medical therapy (GDMT), in normal sinus rhythm (NSR), and with EF ranging from 25% to 45%, and who are ineligible for CRT.Areas covered: Multiple clinical trials support the use of CCM to improve quality of life, functional class, and 6-min hall walk distance. This article will discuss the science behind CCM therapy, the presumed mechanisms of action, the pre-clinical studies that shaped subsequent endeavors, and the clinical trials that support its use.Expert opinion: The introduction of CCM therapy bridges a therapeutic gap for patients with few or no other therapeutic options for NYHA III heart failure.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Contração Miocárdica/fisiologia , Ensaios Clínicos como Assunto , Humanos , Vigilância de Produtos Comercializados , Qualidade de Vida , Resultado do Tratamento
16.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255277

RESUMO

Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Descoberta de Drogas , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Miócitos Cardíacos/citologia , Engenharia Tecidual
17.
J Nippon Med Sch ; 87(5): 268-276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33311008

RESUMO

BACKGROUND: Some cultured neonatal rat cardiomyocytes continue spontaneous beating even in serum-free medium. The present study explored the cause and genes responsible for this phenomenon. METHODS: Ingenuity Pathway Analysis (IPA) software was used to analyze fold changes in gene expression in beating neonatal rat cardiomyocytes, as compared with non-beating cardiomyocytes, which were obtained from DNA microarray data of total RNA extracts of cardiomyocytes. To confirm the involvement of the 8 genes selected by IPA prediction, cellular protein abundances were determined by Western blot. The gene expression of connective tissue growth factor (CTGF) was substantially higher in beating cardiomyocytes than in non-beating cardiomyocytes; thus, CTGF protein content released from cardiomyocytes into the culture medium was examined. RESULTS: IPA showed that the "Apelin Cardiac Fibroblast Signaling Pathway" was significantly inhibited and that microtubule dynamics and cytoskeleton organization were significantly activated. Each fluctuation in the cellular abundances of the 8 proteins in beating cardiomyocytes, as compared with non-beating cardiomyocytes, was primarily in the same direction as that of gene expression. However, the cellular CTGF protein abundance as well as CTGF content released into the medium did not substantially differ between beating and non-beating cardiomyocytes. CONCLUSIONS: The present results suggest that the large increase in CTGF gene expression in beating cardiomyocytes is not a cause but a result of beating, which may provide a putative pathway for controlling beating. Beating is sustained by developed cardiomyofibrils and directly upregulates CTGF gene expression, which is not followed by CTGF protein synthesis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Regulação da Expressão Gênica , Expressão Gênica , Contração Miocárdica/genética , Contração Miocárdica/fisiologia , Miócitos Cardíacos/fisiologia , Regulação para Cima , Animais , Animais Recém-Nascidos , Células Cultivadas , Ratos
18.
World J Pediatr Congenit Heart Surg ; 11(6): 712-719, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33164683

RESUMO

AIMS: Congenital coronary artery anomalies are uncommon and may result in sudden death. Management of asymptomatic patients with anomalous aortic origin of the right coronary artery (AAORCA) remains controversial with a lack of evidence to guide decision-making. We hypothesized that patients with AAORCA may have exercise-inducible ischemia detectable as abnormalities in regional myocardial deformation on exercise stress echocardiography (ESE). METHODS: We reviewed clinical data, computed tomography angiography, and treadmill ESE from 33 AAORCA patients (21 unoperated, 12 operated) and 11 controls. Regional wall motion on ESE was visually assessed. Doppler tissue imaging was done pre and post exercise to evaluate regional myocardial wall deformation. The post- to pre-exercise time to peak systolic strain corrected for heart rate ratio (TPScR) for the left ventricular inferior and anterior walls of AAORCA patients was compared to controls. RESULTS: No regional wall motion abnormalities were noted. The TPScR of the inferior wall was higher in unoperated (0.96 ± 0.41) but not operated (0.84 ± 0.28) AAORCA patients compared to controls (0.76 ± 0.18, P = .03 vs .23, respectively). There was no significant difference in TPScR of the anterior wall between unoperated patients and controls (P = .08). CONCLUSION: In some AAORCA patients undergoing ESE, TPScR of the left ventricular inferior wall is elevated, suggestive of ischemia induced by exercise in myocardium supplied by the right coronary artery. Further work is needed to understand the potential role of this finding in risk assessment.


Assuntos
Aorta Torácica/anormalidades , Circulação Coronária/fisiologia , Anomalias dos Vasos Coronários/diagnóstico , Ecocardiografia sob Estresse/efeitos adversos , Contração Miocárdica/fisiologia , Isquemia Miocárdica/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Anomalias dos Vasos Coronários/complicações , Anomalias dos Vasos Coronários/fisiopatologia , Eletrocardiografia , Teste de Esforço/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Miocárdio , Adulto Jovem
19.
Epilepsia ; 61(10): 2234-2243, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33053223

RESUMO

OBJECTIVE: To test whether children with epilepsy have impairments in myocardial mechanics compared to controls without epilepsy. METHODS: Children with refractory epilepsy with epilepsy duration of at least 3 years underwent echocardiography including conventional measurements and speckle tracking to assess longitudinal and circumferential strain. Parent-completed surveys, capturing critical aspects of the children's seizure history and cardiac risk factors, complemented retrospective chart reviews, which also included antiepileptic drug history. Normal echocardiograms from controls, matched for age and gender, were obtained from our institutional database and evaluated for strain. RESULTS: Forty-one patients (median age = 10 years, interquartile range [IQR] = 5-15; 58.5% male) were enrolled. Epilepsy etiology included genetic (n = 26), structural (n = 6), genetic and structural (n = 5), infection (n = 3), and unknown (n = 1). No cardiac structural abnormalities were identified. Both longitudinal and circumferential strain were impaired (P < .03) in patients compared to controls (median [IQR] = 22.7% [21.2-24.2] vs 23.6% [22.2-26.1] and 22.0% [20.3-25.4] vs 24.5% [22.3-27.0], respectively), indicating decreased myocardial deformation/contraction. Shortening fraction was higher in patients (37.6% [35.7-39.7] vs 34.9% [32.5-38.7], P = .009); mitral valve E wave inflow velocity (84.8 cm/s [78.4-92.8] vs 97.2 cm/s [85.9-105.8], P = .005) and tissue Doppler lateral E' wave (13.9 cm/s [12.3-16.1] vs 17.3 cm/s [15.4-18.5], P < .001) were decreased compared to controls. Findings were similar in the pairs with epilepsy patients distinguished by the ability to independently ambulate. There was no difference between patients and controls in ejection fraction. Among the epilepsy patients, there were no associations between cardiac measurements and epilepsy characteristics, including seizure type and frequency and cardiotoxic antiseizure medication exposure after correction for multiple comparisons. SIGNIFICANCE: Children with refractory epilepsy had impaired systolic ventricular strain compared to controls, not correlated with epilepsy history. Further studies are needed to determine the significance of these changes.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Contração Miocárdica/fisiologia , Morte Súbita Inesperada na Epilepsia/prevenção & controle , Adolescente , Estudos de Casos e Controles , Criança , Epilepsia Resistente a Medicamentos/epidemiologia , Ecocardiografia Doppler/métodos , Feminino , Cardiopatias/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Morte Súbita Inesperada na Epilepsia/epidemiologia
20.
Sci Rep ; 10(1): 17026, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046745

RESUMO

The myocardial contraction fraction (MCF: stroke volume to myocardial volume) is a novel volumetric measure of left ventricular myocardial shortening. The purpose of the present study was to assess whether MCF could predict adverse outcomes for HCM patients. A retrospective cohort study of 438 HCM patients was conducted. The primary and secondary endpoints were all-cause mortality and HCM-related mortality. The association between MCF and endpoints was analysed. During a follow-up period of 1738.2 person-year, 76 patients (17.2%) reached primary endpoint and 50 patients (65.8%) reached secondary endpoint. Both all-cause mortality rate and HCM-related mortality rate decreased across MCF tertiles (24.7% vs. 17.9% vs. 9.5%, P trend = 0.003 for all-cause mortality; 16.4% vs. 9.7% vs. 6.1%, P trend = 0.021 for HCM-related mortality). Patients in the third tertile had a significantly lower risk of developing adverse outcomes than patients in the first tertile: all-cause mortality (adjusted HR: 0.26, 95% CI: 0.12-0.56, P = 0.001), HCM-related mortality (adjusted HR: 0.17, 95% CI: 0.07-0.42, P < 0.001). At 1-, 3-, and 5-year of follow-up, areas under curve were 0.699, 0.643, 0.618 for all-cause mortality and 0.749, 0.661, 0.613 for HCM-related mortality (all P value < 0.001), respectively. In HCM patients, MCF could independently predict all-cause mortality and HCM-related mortality, which should be considered for overall risk assessment in clinical practice.


Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Insuficiência Cardíaca/mortalidade , Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Adulto , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...