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1.
J UOEH ; 42(3): 291-295, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32879194

RESUMO

We report a case of a 77-year-old male who had been diagnosed with normal-flow high-pressure gradient severe aortic stenosis (AS) two years previously. In accordance with his wishes, it was decided not to perform surgery. He visited our hospital with anorexia and weight loss and was diagnosed with gastric cancer. Echocardiography showed a change to paradoxical low-flow low-pressure gradient severe AS (PLFLPG AS). A decrease in stroke volume is typically associated with a smaller LV size, but the reason for a smaller LV size in PLFLPG AS remains unclear. In this case, the change to PLFLPG AS was thought to be due to a decrease in whole body oxygen consumption, and this may help to understand the pathology.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Idoso , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/patologia , Baixo Débito Cardíaco , Progressão da Doença , Ecocardiografia , Ventrículos do Coração/patologia , Humanos , Masculino , Consumo de Oxigênio , Índice de Gravidade de Doença , Neoplasias Gástricas/complicações , Volume Sistólico
2.
Nat Commun ; 11(1): 3955, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769998

RESUMO

Cellular therapy to treat heart failure is an ongoing focus of intense research, but progress toward structural and functional recovery remains modest. Engineered augmentation of established cellular effectors overcomes impediments to enhance reparative activity. Such 'next generation' implementation includes delivery of combinatorial cell populations exerting synergistic effects. Concurrent isolation and expansion of three distinct cardiac-derived interstitial cell types from human heart tissue, previously reported by our group, prompted design of a 3D structure that maximizes cellular interaction, allows for defined cell ratios, controls size, enables injectability, and minimizes cell loss. Herein, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and c-Kit+ cardiac interstitial cells (cCICs) when cultured together spontaneously form scaffold-free 3D microenvironments termed CardioClusters. scRNA-Seq profiling reveals CardioCluster expression of stem cell-relevant factors, adhesion/extracellular-matrix molecules, and cytokines, while maintaining a more native transcriptome similar to endogenous cardiac cells. CardioCluster intramyocardial delivery improves cell retention and capillary density with preservation of cardiomyocyte size and long-term cardiac function in a murine infarction model followed 20 weeks. CardioCluster utilization in this preclinical setting establish fundamental insights, laying the framework for optimization in cell-based therapeutics intended to mitigate cardiomyopathic damage.


Assuntos
Microambiente Celular , Miocárdio/patologia , Cicatrização , Animais , Animais Recém-Nascidos , Capilares/patologia , Agregação Celular , Morte Celular , Linhagem da Célula , Tamanho Celular , Citoproteção , Células Progenitoras Endoteliais/citologia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Processamento de Imagem Assistida por Computador , Recém-Nascido , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos NOD , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/citologia , Estresse Oxidativo , Comunicação Parácrina , Ratos Sprague-Dawley , Transcrição Genética
3.
PLoS One ; 15(7): e0236413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735567

RESUMO

OBJECTIVE: Although a number of modifiable and non-modifiable causes were implicated in arterial stiffness, its pathogenesis remains elusive, and very little is known about aortic elasticity in supraventricular arrhythmias. The potential role of disturbed kynurenine metabolism in the pathogenesis of cardiovascular disease has been recently suggested. Thus, we studied the correlations of aortic stiffness and echocardiographic parameters with biochemical markers and serum level of kynurenic acid (KYNA), an endothelial derivative of tryptophan, formed along the kynurenine pathway, among patients with atrial fibrillation (AF). METHODS: Study cohort comprised 100 patients with persistent AF (43 females/57 males). Arterial stiffness index (ASI), structural and functional indices of left atrium (LA) and left ventricle (LV) were evaluated electrocardiographically. Biochemical analyses included the measurements of serum KYNA (HPLC) and of the selected markers of lipids and glucose metabolism, thyroid status, kidney function, inflammation and coagulation. RESULTS: KYNA (ß = 0.389, P = 0.029), homocysteine (ß = 0.256, P = 0.40), total cholesterol (ß = 0.814; P = 0.044), LDL (ß = 0.663; P = 0.44), TSH (ß = 0.262, P = 0.02), fT3 (ß = -0.333, P = 0.009), fT4 (ß = -0.275, P = 0.043) and creatinine (ß = 0.374, P = 0.043) were independently correlated with ASI. ASI was also independently associated with LV end-systolic diameter (LVEDd; ß = 1.751, P = 0.045), midwall fractional shortening (mFS; ß = -1.266, P = 0.007), ratio mFS/end-systolic stress (mFS/ESS; ß = -0.235, P = 0.026), LV shortening fraction (FS; ß = -0.254, P = 0.017), and LA volume index (LAVI; ß = 0.944, P = 0.022). CONCLUSIONS: In patients with AF, aortic stiffness correlated positively with KYNA, biochemical risk factors of atherosclerosis and with the indices of diastolic dysfunction of LV and LA. Revealed relationship between ASI and KYNA is an original observation, suggesting a potential role of disturbed kynurenine metabolism in the pathogenesis of arterial stiffening. KYNA, synthesis of which is influenced by homocysteine, emerges as a novel, non-classical factor associated with ASI in patients with AF.


Assuntos
Aterosclerose/sangue , Fibrilação Atrial/sangue , Biomarcadores/sangue , Ácido Cinurênico/sangue , Adulto , Aorta/diagnóstico por imagem , Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Fibrilação Atrial/fisiopatologia , Estudos Transversais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Rigidez Vascular/fisiologia
4.
J Cardiovasc Magn Reson ; 22(1): 49, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600420

RESUMO

BACKGROUND: The right ventricle (RV) often fails when functioning as the systemic ventricle, but the cause is not understood. We tested the hypothesis that myofiber organization is abnormal in the failing systemic right ventricle. METHODS: We used diffusion-weighted cardiovascular magnetic resonance imaging to examine 3 failing hearts explanted from young patients with a systemic RV and one structurally normal heart with postnatally acquired RV hypertrophy for comparison. Diffusion compartment imaging was computed to separate the free diffusive component representing free water from an anisotropic component characterizing the orientation and diffusion characteristics of myofibers. The orientation of each anisotropic compartment was displayed in glyph format and used for qualitative description of myofibers and for construction of tractograms. The helix angle was calculated across the ventricular walls in 5 locations and displayed graphically. Scalar parameters (fractional anisotropy and mean diffusivity) were compared among specimens. RESULTS: The hypertrophied systemic RV has an inner layer, comprising about 2/3 of the wall, composed of hypertrophied trabeculae and an epicardial layer of circumferential myofibers. Myofibers within smaller trabeculae are aligned and organized with parallel fibers while larger, composite bundles show marked disarray, largely between component trabeculae. We observed a narrow range of helix angles in the outer, compact part of the wall consistent with aligned, approximately circumferential fibers. However, there was marked variation of helix angle in the inner, trabecular part of the wall consistent with marked variation in fiber orientation. The apical whorl was disrupted or incomplete and we observed myocardial whorls or vortices at other locations. Fractional anisotropy was lower in abnormal hearts while mean diffusivity was more variable, being higher in 2 but lower in 1 heart, compared to the structurally normal heart. CONCLUSIONS: Myofiber organization is abnormal in the failing systemic RV and might be an important substrate for heart failure and arrhythmia. It is unclear if myofiber disorganization is due to hemodynamic factors, developmental problems, or both.


Assuntos
Imagem de Difusão por Ressonância Magnética , Cardiopatias Congênitas/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Miofibrilas/patologia , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Direita , Adolescente , Pré-Escolar , Feminino , Cardiopatias Congênitas/patologia , Cardiopatias Congênitas/fisiopatologia , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Ventrículos do Coração/cirurgia , Humanos , Masculino , Valor Preditivo dos Testes , Disfunção Ventricular Direita/patologia , Disfunção Ventricular Direita/fisiopatologia , Disfunção Ventricular Direita/cirurgia , Adulto Jovem
5.
PLoS One ; 15(7): e0235433, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726316

RESUMO

ADP-ribosylhydrolase-like 1 (Adprhl1) is a pseudoenzyme expressed in the developing heart myocardium of all vertebrates. In the amphibian Xenopus laevis, knockdown of the two cardiac Adprhl1 protein species (40 and 23 kDa) causes failure of chamber outgrowth but this has only been demonstrated using antisense morpholinos that interfere with RNA-splicing. Transgenic production of 40 kDa Adprhl1 provides only part rescue of these defects. CRISPR/Cas9 technology now enables targeted mutation of the adprhl1 gene in G0-generation embryos with routine cleavage of all alleles. Testing multiple gRNAs distributed across the locus reveals exonic locations that encode critical amino acids for Adprhl1 function. The gRNA recording the highest frequency of a specific ventricle outgrowth phenotype directs Cas9 cleavage of an exon 6 sequence, where microhomology mediated end-joining biases subsequent DNA repairs towards three small in-frame deletions. Mutant alleles encode discrete loss of 1, 3 or 4 amino acids from a di-arginine (Arg271-Arg272) containing peptide loop at the centre of the ancestral ADP-ribosylhydrolase site. Thus despite lacking catalytic activity, it is the modified (adenosine-ribose) substrate binding cleft of Adprhl1 that fulfils an essential role during heart formation. Mutation results in striking loss of myofibril assembly in ventricle cardiomyocytes. The defects suggest Adprhl1 participation from the earliest stage of cardiac myofibrillogenesis and are consistent with previous MO results and Adprhl1 protein localization to actin filament Z-disc boundaries. A single nucleotide change to the gRNA sequence renders it inactive. Mice lacking Adprhl1 exons 3-4 are normal but production of the smaller ADPRHL1 species is unaffected, providing further evidence that cardiac activity is concentrated at the C-terminal protein portion.


Assuntos
Ventrículos do Coração/crescimento & desenvolvimento , Coração/crescimento & desenvolvimento , Desenvolvimento Muscular/genética , N-Glicosil Hidrolases/genética , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/crescimento & desenvolvimento , Catálise , Domínio Catalítico/genética , Coração/fisiopatologia , Ventrículos do Coração/patologia , Humanos , Camundongos , Camundongos Knockout , Morfolinos/genética , Oligodesoxirribonucleotídeos Antissenso/genética , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Organogênese/genética , Xenopus laevis/genética , Xenopus laevis/crescimento & desenvolvimento
6.
BMC Infect Dis ; 20(1): 476, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631238

RESUMO

BACKGROUND: Blood culture-negative endocarditis (BCNE) is diagnosed in 2-7% of patients with infective endocarditis (IE) and recent antibiotic use is a known risk factor. Altered mental status may be a presenting symptom. Besides empiric antibiotics, intravenous anticoagulation using heparin may have a role in the management of such patients. CASE PRESENTATION: A 23-year-old male patient was referred to our center with fever, altered mental status and abnormal gait. Neurologic examination revealed Wernicke's aphasia. Cardiac auscultation revealed systolic murmur at the left sternal border. ECG (electrocardiogram) was unremarkable. Brain MRI showed multiple cerebellar lesions. Transthoracic echocardiography (TTE) demonstrated three large masses on the right ventricle (RV), tricuspid valve (TV), and anterior mitral valve (MV) leaflet. Blood cultures (three sets) were negative. Intravenous heparin therapy was administered. After 48 h, the second TTE demonstrated that one valvular lesion disappeared and the other two lesions showed a significant decrease in size. The patient's neurological symptoms resolved gradually. Further workup for collagen vascular disorders did not show any abnormality. CONCLUSION: BCNE should be considered in patients with fever and neurologic manifestations. TTE should be performed to detect valvular abnormalities. Intravenous heparin could be used in such patients when TTE demonstrate valvular vegetations.


Assuntos
Anticoagulantes/uso terapêutico , Afasia de Wernicke/tratamento farmacológico , Hemocultura , Ecocardiografia , Endocardite Bacteriana/diagnóstico por imagem , Heparina/uso terapêutico , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Anticoagulantes/administração & dosagem , Afasia de Wernicke/microbiologia , Endocardite Bacteriana/sangue , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Heparina/administração & dosagem , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Valva Mitral/patologia , Resultado do Tratamento , Valva Tricúspide/diagnóstico por imagem , Valva Tricúspide/patologia , Adulto Jovem
7.
J Comput Assist Tomogr ; 44(4): 586-590, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697529

RESUMO

BACKGROUND: The clinical relevance and anatomic characteristics of intracavitary coronary arteries coursing within the right ventricle (RV) are largely unknown. OBJECTIVES: The aim of our study was to assess the clinical and computed tomographic characteristics of patients diagnosed with intracavitary coronary arteries coursing within RV (intra-RV coronaries). METHODS: Electronic records from a single high-volume cardiac center were retrospectively screened for the presence of intra-RV coronaries among consecutive patients who underwent coronary computed tomography angiography (coronary CTA) from 2008 to 2019. RESULTS: Overall, 31,748 coronary CTA reports were evaluated, and 17 subjects with intra-RV coronaries were identified. None of these patients was referred for subsequent invasive coronary angiography. One patient underwent coronary artery bypass grafting, 1 patient had a history of percutaneous coronary intervention, and 1 patient had a concomitant coronary anomaly: left circumflex coronary artery originating from the right coronary artery. All of the involved coronaries (n = 17) were the left anterior descending coronary arteries (LADs). Typical segmental coronary course within RV was along the border between free RV wall and interventricular septum (beneath interventricular groove), often within trabeculae carneae of the RV. Only the midsegment and distal segment of the LAD traversed within the RV. The mean ± SD distance from the aorta to the coronary entrance into the RV was 74.5 ± 17.1 mm, whereas the mean ± SD intra-RV coronary length was 25.1 ± 14.0 mm. CONCLUSIONS: Intra-RV course of the coronaries in an adult CTA population is an infrequent anatomical variant involving LAD. It may require additional attention during interventional and surgical interventions.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Idoso , Anomalias dos Vasos Coronários/patologia , Feminino , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
PLoS One ; 15(7): e0236490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716921

RESUMO

Individuals with spinal cord injury develop cardiovascular disease more than age-matched, non-injured cohorts. However, progression of systolic and diastolic dysfunction into cardiovascular disease after spinal cord injury is not well described. We sought to investigate the relationship between systolic and diastolic function in chronic spinal cord injury to describe how biological sex, level, severity, and duration of injury correlate with structural changes in the left ventricle. Individuals with chronic spinal cord injury participated in this study (n = 70). Registered diagnostic cardiac sonographers used cardiac ultrasound to measure dimensions, mass, and systolic and diastolic function of the left ventricle. We found no significant relationship to severity or duration of injury with left ventricle measurements, systolic function outcome, or diastolic function outcome. Moreover, nearly all outcomes measured were within the American Society of Echocardiography-defined healthy range. Similar to non-injured individuals, when indexed by body surface area (BSA) left ventricle mass [-14 (5) g/m2, p < .01], end diastolic volume [-6 (3) mL/m2, p < .05], and end systolic volume [-4 (1) mL/m2, p < .01] were significantly decreased in women compared with men. Likewise, diastolic function outcomes significantly worsened with age: E-wave velocity [-5 (2), p < .01], E/A ratio [-0.23 (0.08), p < .01], and e' velocity [lateral: -1.5 (0.3) cm/s, p < .001; septal: -0.9 (0.2), p < .001] decreased with age while A-wave velocity [5 (1) cm/s, p < .001] and isovolumic relaxation time [6 (3) ms, p < .05] increased with age. Women demonstrated significantly decreased cardiac size and volumes compared with men, but there was no biological relationship to dysfunction. Moreover, individuals were within the range of ASE-defined healthy values with no evidence of systolic or diastolic function and no meaningful relationship to level, severity, or duration of injury. Decreases to left ventricular dimensions and mass seen in spinal cord injury may result from adaptation rather than maladaptive myocardial remodeling, and increased incidence of cardiovascular disease may be related to modifiable risk factors.


Assuntos
Diástole/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Sístole/fisiologia , Adulto , Pressão Sanguínea , Feminino , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Análise Multivariada , Tamanho do Órgão
9.
Nat Commun ; 11(1): 2843, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32487995

RESUMO

Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5-monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil gender-specific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Isquemia Miocárdica/metabolismo , Caracteres Sexuais , Transdução de Sinais , Cardiomiopatia Dilatada/patologia , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Isquemia Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Análise de Componente Principal , Mapas de Interação de Proteínas , Proteoma/metabolismo , Proteômica , Doadores de Tecidos
10.
Cardiovasc Pathol ; 48: 107224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32480283

RESUMO

OBJECTIVE: We used automated image analysis software to determine the proportion of collagen, fat, and myocytes across six histological regions of normal ventricular myocardium. METHODS: Twenty-nine non-cardiac death cases referred to our national cardiac pathology center were included in this study. Whole hearts were macroscopically and microscopically normal following expert histopathological evaluation. Tissue sections from the right ventricular outflow tract, right ventricle (RV), anterior interventricular septum (IVS), posterior IVS, anterior left ventricle (LV), and posterior LV were stained with Picrosirius red for collagen and scanned using a high-resolution slide scanner. Quantification of collagen, fat, and myocyte proportions was performed using Visiopharm software after automated exclusion of perivascular collagen. RESULTS: The majority of decedents were male (25/29; 86%) with a mean age at death of 32.1 ± 9.9 (range 18-54) and mean BMI 28.7 ± 7.3. We report predicted values (collagen %, fat %, myocytes %) for cardiac tissue composition within the RV, IVS, and LV (including epicardial and endocardial layers). The proportion of collagen and fat were higher in the RV compared with the LV (ratios 1.61 [1.45-1.78]; 2.63 [1.99-3.48], respectively) and RV compared with the IVS (ratios 1.77 [1.60-1.97]; 8.41[6.35-11.13], respectively). The ratio of epicardial versus endocardial fat was increased in both ventricles (RV: ratio 4.49 [3.67-5.49]; LV: ratio 3.46 [2.49-4.81]). In multivariable analysis, there was no significant association between collagen or fat proportion and sex (p=0.12; p=0.08, respectively), age at death (p=0.36; p=0.23, respectively), or BMI (p=0.45; p=0.43, respectively). CONCLUSIONS: Our findings provide location and sex-specific proportions of myocardial histological tissue composition that may aid quantitative evaluation of pathology in future studies.


Assuntos
Tecido Adiposo/patologia , Colágeno/análise , Ventrículos do Coração/química , Ventrículos do Coração/patologia , Miócitos Cardíacos/química , Miócitos Cardíacos/patologia , Adolescente , Adulto , Autopsia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Adulto Jovem
11.
PLoS One ; 15(6): e0234087, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32511282

RESUMO

BACKGROUND: Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches. METHODS: Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactide-co-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation. RESULT: Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups. CONCLUSION: We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Engenharia Tecidual , Implantes Absorvíveis , Animais , Modelos Animais de Doenças , Ecocardiografia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/transplante , Poliésteres/química , Ácido Poliglicólico/química , Ratos , Ratos Nus , Tecidos Suporte/química , Troponina T/metabolismo , Função Ventricular
12.
Can J Cardiol ; 36(8): 1326.e9-1326.e11, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32599017

RESUMO

A wide spectrum of cardiovascular manifestations has been documented in patients suffering from coronavirus disease-2019 (COVID-19). Usually associated with a poor prognoses, these manifestations include thromboembolic events, acute coronary syndrome, heart failure, and cardiogenic shock. We describe a patient with COVID-19 who presented with subacute myocardial infarction, biventricular thrombi, and bilateral pulmonary emboli. Biventricular thrombi are rare, and their presence raises concern for an underlying prothrombotic condition.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus , Aneurisma Cardíaco , Ventrículos do Coração , Pandemias , Pneumonia Viral , Embolia Pulmonar , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombose , Anticoagulantes/administração & dosagem , Reanimação Cardiopulmonar/métodos , Deterioração Clínica , Angiografia Coronária/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Evolução Fatal , Feminino , Aneurisma Cardíaco/diagnóstico , Aneurisma Cardíaco/etiologia , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Trombose/diagnóstico , Trombose/tratamento farmacológico , Trombose/etiologia , Tomografia Computadorizada por Raios X/métodos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia
13.
PLoS One ; 15(6): e0235220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584885

RESUMO

BACKGROUND: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied. EXPERIMENTAL APPROACH: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. RESULTS: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP. DISCUSSION: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences.


Assuntos
Pinos Ortopédicos/efeitos adversos , Fraturas do Fêmur/cirurgia , Traumatismo Múltiplo/patologia , Miocárdio/patologia , Actinina/metabolismo , Animais , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular , Conexina 43/metabolismo , Citocinas/análise , Citocinas/metabolismo , Desmina/metabolismo , Fraturas do Fêmur/patologia , Proteína HMGB1/análise , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Inflamação , Masculino , Camundongos , Traumatismo Múltiplo/metabolismo , Traumatismo Múltiplo/veterinária , Miocárdio/metabolismo , Estresse Nitrosativo , Suínos , Troponina I/análise
14.
Mem Inst Oswaldo Cruz ; 115: e200056, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32556037

RESUMO

BACKGROUND: Left ventricular aneurysm (LVA) is indicator of high morbidity in Chagas' disease. A cross-sectional study performed identified LVA in 18.8% of the chronic chagasic patients (CCP). OBJECTIVE: Determine the risk of death of patients with chronic chagasic cardiopathy (CCC) and LVA in 24-year interval. MATERIAL AND METHODS: In 1995 a cohort of 298 CCP was evaluated by anamnesis, physical examination, EKG and ECHO and classified in groups: G0 = 86 without cardiopathy; G1 = 156 with cardiopathy without LVA and G2 = 56 with cardiopathy and LVA. 38 patients of G0 and G1 used benznidazole. Information about the deaths was obtained in the notary, death certificates, hospital records and family members. FINDINGS: Were registered 113 deaths (37.9%): 107 (35.9%) attributed to cardiopathy and 6 (2.0%) to other causes (p < 0.05). Amongst these 107 deaths, 10 (11.6%) occurred in G0; 49 (31.4%) occurred in G1 and 48 (85.7%) occurred in G2 (p < 0.05). The risk of death was 2.7 and 7.4 times significantly higher in G2, than in G1 and G0, respectively. CONCLUSION: Chronic chagasic patients with LVA and ejection fraction < 45% have a higher risk of death than those without.


Assuntos
Cardiomiopatia Chagásica/mortalidade , Aneurisma Cardíaco/mortalidade , Ventrículos do Coração/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Cardiomiopatia Chagásica/complicações , Doença Crônica , Estudos Transversais , Eletrocardiografia , Feminino , Aneurisma Cardíaco/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
PLoS One ; 15(5): e0233310, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428014

RESUMO

BACKGROUND: No study has compared the clinical impact of indexation of left ventricular mass (LVM) on adverse clinical outcomes in pre-dialysis patients with chronic kidney disease (CKD). METHODS: We reviewed 2,101 patients from a large-scale multi-center prospective study that gathered anthropometric and echocardiographic measurements and clinical outcomes. The LVM was indexed as body surface area (LVMI-BSA) and height raised to the power of 2.7 (LVMI-H2.7). The main outcomes were composite renal and cardiovascular events and all-cause mortality. Left ventricular hypertrophy (LVH) was defined as the highest sex-specific quartile of LVMI-BSA or LVMI-H2.7. RESULTS: During a mean period of 3.5 years, 692 patients developed composite outcomes (32.9%). The area under the curve at 5 year of LVM (60.6%) for composite outcome was smaller than that for LVMI-BSA (63.2%, P <0.001) and LVMI-H2.7 (63.4%, P <0.001). The hazard ratio (HR) and 95% confidence interval (CI) per one unit increase in LVM (g), LVMI-BSA (g/m2), and LVMI-H2.7 (g/m2.7) for composite outcomes were 1.004 (1.002-1.005, P <0.001), 1.011 (1.006-1.016, P <0.001), and 1.023 (1.012-1.035, P <0.001), respectively. Patients with LVH determined by LVMI-BSA and LVMI-H2.7 (HR 1.352, 95% CI 1.123-1.626, P = 0.001) and LVH determined by only LVMI-BSA (HR 1.908, 95% CI 1.233-2.953, P = 0.004) showed an independent increase in the risk of composite-outcome development, when compared with patients without LVH, according to LVMI-BSA and LVMI-H2.7. CONCLUSION: Indexation of LVM improved the prediction of adverse outcomes. BSA may be as useful as height2.7 in indexing of LVM for predicting adverse outcomes in pre-dialysis patients with CKD.


Assuntos
Ventrículos do Coração/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Adulto , Pressão Sanguínea , Superfície Corporal , Estudos de Coortes , Diálise , Ecocardiografia/métodos , Feminino , Humanos , Hipertrofia Ventricular Esquerda/metabolismo , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , República da Coreia
16.
Am J Physiol Heart Circ Physiol ; 319(1): H183-H191, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32469637

RESUMO

In pulmonary hypertension (PH) a proinflammatory milieu drives pulmonary vascular remodeling, maladaptive right ventricular (RV) remodeling, and right-sided heart failure. There is an unmet need for RV-targeted pharmaco-therapies to improve mortality. Targeting of the P2X7 receptor (P2X7R) reduces pulmonary pressures; however, its effects on the RV are presently unknown. We investigated the effect of P2X7 receptor (P2X7R) inhibition on the pulmonary vasculature and RV remodeling using the novel P2X7R antagonist PKT100. C57BL/6 mice were administered intratracheal bleomycin or saline and treated with PKT100 (0.2 mg·kg-1·day-1) or DMSO vehicle. RV was assessed by right heart catheterization and echocardiography, 21 days posttreatment. Cytokines in serum and bronchoalveolar lavage fluid (BALF) were analyzed by ELISA and flow cytometry. Lungs and hearts were analyzed histologically for pulmonary vascular and RV remodeling. Focused-PCR using genes involved in RV remodeling was performed. Right ventricular systolic pressure (RVSP) was elevated in bleomycin-treated mice (30.2 ± 1.1; n = 7) compared with control mice (23.5 ± 1.0; n = 10; P = 0.008). PKT100 treatment did not alter RVSP (32.4 ± 1.8; n = 9), but it substantially improved survival (93% vs. 57% DMSO). There were no differences between DMSO and PKT100 bleomycin mice in pulmonary inflammation or remodeling. However, RV hypertrophy was reduced in PKT100 mice. Bleomycin decreased echocardiographic surrogates of RV systolic performance, which were significantly improved with PKT100. Four genes involved in RV remodeling (RPSA, Rplp0, Add2, and Scn7a) were differentially expressed between DMSO and PKT100-treated groups. The novel P2X7R inhibitor, PKT100, attenuates RV hypertrophy and improves RV contractile function and survival in a mouse model of PH independently of effects on the pulmonary vasculature. PKT100 may improve ventricular response to increased afterload and merits further investigation into the potential role of P2X7R antagonists as direct RV-focused therapies in PH.NEW & NOTEWORTHY This study demonstrates the therapeutic potential for right-sided heart failure of a novel inhibitor of the P2X7 receptor (P2X7R). Inflammatory signaling and right ventricular function were improved in a mouse model of pulmonary fibrosis with secondary pulmonary hypertension when treated with this inhibitor. Importantly, survival was also improved, suggesting that this inhibitor, and other P2X7R antagonists, could be uniquely effective in right ventricle (RV)-targeted therapy in pulmonary hypertension. This addresses a major limitation of current treatment options, where the significant improvements in pulmonary pressures ultimately do not prevent mortality due to RV failure.


Assuntos
Ventrículos do Coração/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Animais , Pressão Sanguínea , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/sangue , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Antagonistas do Receptor Purinérgico P2X/farmacologia , Receptores de Laminina/genética , Receptores de Laminina/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Remodelação Ventricular , Canais de Sódio Disparados por Voltagem/genética , Canais de Sódio Disparados por Voltagem/metabolismo
17.
Am J Kidney Dis ; 76(2): 166-173, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32389356

RESUMO

RATIONALE & OBJECTIVE: Traditional and nontraditional cardiovascular disease risk factors are highly prevalent in children with chronic kidney disease (CKD). We examined the longitudinal association of adiposity with cardiac damage among children with CKD and explored whether this association was modified by sex. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study at 49 pediatric nephrology centers across North America. EXPOSURE: Age- and sex-specific body mass index (BMI) z score. OUTCOME: Age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy (LVH). ANALYTICAL APPROACH: Longitudinal analyses using mixed-effects models to estimate sex-specific associations of BMI z scores with LVMI z score and with LVH, accounting for repeated measurements over time. RESULTS: Among 725 children with 2,829 person-years of follow-up, median age was 11.0 years and median estimated glomerular filtration rate was 52.6mL/min/1.73m2. Nearly one-third of both boys and girls were overweight or obese, median LVMI z score was 0.18 (IQR: -0.67, 1.08), and 11% had LVH. Greater BMI z scores were independently associated with greater LVMI z scores and greater odds of LVH. For each 1-unit higher BMI z score, LVMI z score was 0.24 (95% CI, 0.17-0.31) higher in boys and 0.38 (95% CI, 0.29-0.47) higher in girls (Pinteraction = 0.01). For each 1-unit higher BMI z score, the odds of LVH was 1.5-fold (95% CI, 1.1-2.1) higher in boys and 3.1-fold (95% CI, 1.8-4.4) higher in girls (Pinteraction = 0.005). LIMITATIONS: Not all children had repeated measurements. LVH is a surrogate and not a hard cardiac outcome. The observational design limits causal inference. CONCLUSIONS: In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.


Assuntos
Hipertrofia Ventricular Esquerda/epidemiologia , Obesidade Pediátrica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adolescente , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Criança , Comorbidade , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Estudos Longitudinais , Masculino , Tamanho do Órgão , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos/epidemiologia
18.
Clin Sci (Lond) ; 134(11): 1191-1218, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32432676

RESUMO

Myocardial infarction (MI) is the leading cause of mortality worldwide. Interleukin (IL)-33 (IL-33) is a cytokine present in most cardiac cells and is secreted on necrosis where it acts as a functional ligand for the ST2 receptor. Although IL-33/ST2 axis is protective against various forms of cardiovascular diseases, some studies suggest potential detrimental roles for IL-33 signaling. The aim of the present study was to examine the effect of IL-33 administration on cardiac function post-MI in mice. MI was induced by coronary artery ligation. Mice were treated with IL-33 (1 µg/day) or vehicle for 4 and 7 days. Functional and molecular changes of the left ventricle (LV) were assessed. Single cell suspensions were obtained from bone marrow, heart, spleen, and peripheral blood to assess the immune cells using flow cytometry at 1, 3, and 7 days post-MI in IL-33 or vehicle-treated animals. The results of the present study suggest that IL-33 is effective in activating a type 2 cytokine milieu in the damaged heart, consistent with reduced early inflammatory and pro-fibrotic response. However, IL-33 administration was associated with worsened cardiac function and adverse cardiac remodeling in the MI mouse model. IL-33 administration increased infarct size, LV hypertrophy, cardiomyocyte death, and overall mortality rate due to cardiac rupture. Moreover, IL-33-treated MI mice displayed a significant myocardial eosinophil infiltration at 7 days post-MI when compared with vehicle-treated MI mice. The present study reveals that although IL-33 administration is associated with a reparative phenotype following MI, it worsens cardiac remodeling and promotes heart failure.


Assuntos
Eosinófilos/metabolismo , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Interleucina-33/farmacologia , Infarto do Miocárdio/fisiopatologia , Sístole/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Citocinas/sangue , Fragmentação do DNA/efeitos dos fármacos , Diástole/efeitos dos fármacos , Eosinofilia/patologia , Eosinófilos/efeitos dos fármacos , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/patologia , Mediadores da Inflamação/sangue , Interleucina-33/administração & dosagem , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esplenomegalia/patologia , Regulação para Cima/efeitos dos fármacos , Remodelação Ventricular/genética , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
19.
Am J Cardiol ; 127: 139-141, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32375998

RESUMO

Hypertrophic cardiomyopathy (HC) is associated with a well-recognized risk for unexpected sudden death (SD). Most such reported patients have been referred to dedicated centers and/or expert cardiologists for risk stratification, with the number of SDs decreasing sharply due to penetration of the implantable cardioverter-defibrillator (ICDs) into HC practice. However, the clinical circumstances, and morphologic features of HC patients who incur SD without the opportunity to be considered for preventive intervention with ICDs are largely undefined. Using the long-standing unique Jesse Edwards Registry (St. Paul, Minnesota), we studied 86 selected heart specimens from young HC patients who died suddenly and unexpectedly without prior clinical evaluation, ages 31 ± 16 years. The patients were predominantly male (87%) with only modest phenotypic expression and maximum LV wall thickening of only 18 ± 4 mm. SD events occurred predominantly with sedentary/mild activities (66%) often in bed or asleep (32%), but also during physical activity (22%) including with organized competitive sports. This largely unappreciated sub-population of patients with HC (and SD) is characterized by mild-to-moderate degree of LV hypertrophy, representing a clinical challenge which is particularly relevant in the current ICD era for HC, with the potential for SD prevention.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Morte Súbita Cardíaca/etiologia , Ventrículos do Coração/patologia , Autopsia , Cardiomiopatia Hipertrófica/complicações , Morte Súbita Cardíaca/patologia , Humanos
20.
Am J Physiol Heart Circ Physiol ; 319(1): H109-H122, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442025

RESUMO

Although cell therapy-mediated cardiac repair offers promise for treatment/management of heart failure, lack of fundamental understanding of how cell therapy works limits its translational potential. In particular, whether reparative cells from failing hearts differ from cells derived from nonfailing hearts remains unexplored. Here, we assessed differences between cardiac mesenchymal cells (CMC) derived from failing (HF) versus nonfailing (Sham) hearts and whether the source of donor cells (i.e., from HF vs. Sham) limits reparative capacity, particularly when administered late after infarction. To determine the impact of the donor source of CMCs, we characterized the transcriptional profile of CMCs isolated from sham (Sham-CMC) and failing (HF-CMC) hearts. RNA-seq analysis revealed unique transcriptional signatures in Sham-CMC and HF-CMC, suggesting that the donor source impacts CMC. To determine whether the donor source affects reparative potential, C57BL6/J female mice were subjected to 60 min of regional myocardial ischemia and then reperfused for 35 days. In a randomized, controlled, and blinded fashion, vehicle, HF-CMC, or Sham-CMC were injected into the lumen of the left ventricle at 35 days post-MI. An additional 5 weeks later, cardiac function was assessed by echocardiography, which indicated that delayed administration of Sham-CMC and HF-CMC attenuated ventricular dilation. We also determined whether Sham-CMC and HF-CMC treatments affected ventricular histopathology. Our data indicate that the donor source (nonfailing vs. failing hearts) affects certain aspects of CMC, and these insights may have implications for future studies. Our data indicate that delayed administration of CMC limits ventricular dilation and that the source of CMC may influence their reparative actions.NEW & NOTEWORTHY Most preclinical studies have used only cells from healthy, nonfailing hearts. Whether donor condition (i.e., heart failure) impacts cells used for cell therapy is not known. We directly tested whether donor condition impacted the reparative effects of cardiac mesenchymal cells in a chronic model of myocardial infarction. Although cells from failing hearts differed in multiple aspects, they retained the potential to limit ventricular remodeling.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Função Ventricular , Animais , Células Cultivadas , Feminino , Ventrículos do Coração/citologia , Ventrículos do Coração/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transcriptoma
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