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3.
J Korean Med Sci ; 35(39): e349, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045772

RESUMO

BACKGROUNDS: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has spread worldwide. Cardiac injury after SARS-CoV-2 infection is a major concern. The present study investigated impact of the biomarkers indicating cardiac injury in coronavirus disease 2019 (COVID-19) on patients' outcomes. METHODS: This study enrolled patients who were confirmed to have COVID-19 and admitted at a tertiary university referral hospital between February 19, 2020 and March 15, 2020. Cardiac injury was defined as an abnormality in one of the following result markers: 1) myocardial damage marker (creatine kinase-MB or troponin-I), 2) heart failure marker (N-terminal-pro B-type natriuretic peptide), and 3) electrical abnormality marker (electrocardiography). The relationship between each cardiac injury marker and mortality was evaluated. Survival analysis of mortality according to the scoring by numbers of cardiac injury markers was also performed. RESULTS: A total of 38 patients with COVID-19 were enrolled. Twenty-two patients (57.9%) had at least one of cardiac injury markers. The patients with cardiac injuries were older (69.6 ± 14.9 vs. 58.6 ± 13.9 years old, P = 0.026), and were more male (59.1% vs. 18.8%, P = 0.013). They showed lower initial oxygen saturation (92.8 vs. 97.1%, P = 0.002) and a trend toward higher mortality (27.3 vs. 6.3%, P = 0.099). The increased number of cardiac injury markers was significantly related to a higher incidence of in-hospital mortality which was also evidenced by Kaplan-Meier survival analysis (P = 0.008). CONCLUSION: The increased number of cardiac injury markers is related to in-hospital mortality in patients with COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Miocárdio/metabolismo , Pneumonia Viral/diagnóstico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Creatina Quinase Forma MB/metabolismo , Eletrocardiografia , Feminino , Traumatismos Cardíacos/metabolismo , Traumatismos Cardíacos/patologia , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Peptídeo Natriurético Encefálico/metabolismo , Pandemias , Fragmentos de Peptídeos/metabolismo , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Fatores Sexuais , Centros de Atenção Terciária , Troponina I/metabolismo
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2557-2560, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018528

RESUMO

The heat production of cardiac muscle, determined by calorimetry, can be used as a measure of cardiac metabolism. However, heat produced while a muscle is actively-shortening, thereby performing force-length work, comprises both active and basal metabolic processes. In this paper, we present a method for post-experimental processing of calorimetric measurements of muscle heat production, that uncovers and compensates for the measured basal heat rate during work. In this method, the relationships between muscle length, velocity of length change and muscle heat output are coupled with a simulation of the measurement instrument, providing a model-based estimate of change of measured basal heat while the muscle is performing work. We demonstrate the use of this technique in an experiment conducted on a working cardiac muscle sample. The ability to identify the various components of heat release in these muscles provides useful insight into their mechanical and energetic capabilities.


Assuntos
Miocárdio , Termogênese , Metabolismo Basal , Calorimetria , Descanso
5.
Wiad Lek ; 73(8): 1712-1716, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33055339

RESUMO

OBJECTIVE: The aim: Study of the patterns of structural changes in the left ventricular myocardial capillaries of rats with arterial hypertension with combined pharmacotherapy with Bisoprolol and Thiotriazolinum. PATIENTS AND METHODS: Materials and methods: Experiments were conducted on 30 line rats with congenital stress-induced arterial hypertension: 10 animals without treatment and 10 animals with treatment. Pharmacological correction of spontaneous arterial hypertension was performed with 20 mg / kg of Bisoprolol and 50 mg / kg of Thiotriazolinum per os once a day. Pharmacotherapy began at 5 months of age, that is, at a time when compensated heart failure was formed in rats with arterial hypertension. Animals were withdrawn from the experiment 100 days after the start of the correction. Control was provided by intact animals (10 rats) of the corresponding age. While extracted from the experiment rats of all experimental groups had their arterial pressure measured using a plethysmograph, electron microscopic examination of the left ventricular myocardium and morphometric study of volumetric and quantitative densities, cross-section area and form factor of micropinocytotic vesicles were conducted. RESULTS: Results: In rats with arterial hypertension after application of Bisoprolol and Thiotriazolinum, arterial pressure significantly decreases in experimental rats compared to animals without correction. The number of capillaries in the myocardium after pharmacotherapy increases up to control values, which shows their reparation. In most endothelial cells, organelles retain their integrity and presence that are characteristic of intact rats. The well-expressed processes of transcytosis are shown by the statistical similarity of the quantitative density and the size of the micropinocytotic vesicles in the endothelial cells of the myocardium capillaries of compared experimental animals. CONCLUSION: Conclusions: In rats with arterial hypertension, the combination of Bisoprolol and Thiotriazolinum prevents the decrease in the number of capillaries in the myocardium of the left ventricle, promotes the preservation of the ultrastructure of their endothelial cells and maintains the processes of transedothelial transfer of substances at the level of intact animals.


Assuntos
Células Endoteliais , Hipertensão , Animais , Bisoprolol/uso terapêutico , Coração , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Miocárdio , Ratos
6.
J Oleo Sci ; 69(10): 1287-1295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33028753

RESUMO

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol.


Assuntos
Cardiotônicos , Álcoois Graxos/farmacologia , Álcoois Graxos/uso terapêutico , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Fígado/metabolismo , Fígado/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Oryza/química , PPAR gama/genética , PPAR gama/metabolismo , Fitoterapia , Ceras/química , Animais , Dieta Hiperlipídica/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Homocisteína/sangue , Hiperlipidemias/etiologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley
7.
Turk Kardiyol Dern Ars ; 48(7): 703-706, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33034578

RESUMO

The clinical presentation of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, can range from only mild, flu-like symptoms to severe progressive pneumonia. Cardiac involvement may be observed during the course of the infection and may include myocarditis, acute myocardial infarction, heart failure, and cardiac rhythm disturbances, but cases describing cardiac tamponade in patients previously diagnosed with COVID-19 are very rare. A 58-year-old female had been hospitalized in another hospital 2 weeks prior to the currently described presentation due to atypical pneumonia. A nasopharyngeal swab specimen was positive for COVID-19. The hospitalization was uncomplicated and she was discharged after a week. She presented at our emergency department with symptoms of shortness of breath and swelling in both legs. A bedside transthoracic echocardiography showed globally depressed left ventricular contraction with an ejection fraction of 30% and there was significant pericardial effusion, which surrounded the entire heart and restricted diastolic filling. The patient was admitted to the coronary intensive care unit with the diagnosis of pericardial tamponade. Bedside pericardiocentesis was performed and serohemorrhagic fluid was drained. Pericardial effusion and pericardial tamponade should be considered in the differential diagnosis of patients with COVID-19 exhibiting dyspnea or worsening of dyspnea. A 58-year-old female has been hospitalized in another hospital two weeks ago due to atypical pneumonia. Her nasopharyngeal swab specimen was positive for COVID-19. She had an uncomplicated course during the hospitalization and was discharged a week ago. She presented to our emergency department (ED) with symptoms of shortness of breath and swelling in both legs. We performed bedside transthoracic echocardiography (TTE) which showed globally depressed left ventricular contraction with ejection fraction (EF) of 30% and there was significant pericardial effusion which surrounded the entire heart and restricted diastolic filling. The patient was admitted to the coronary intensive care unit (CICU) with the diagnosis of pericardial tamponade. Bedside pericardiosentesis was performed and serohemorrhagic fluid was drained. Patients with COVID-19 infection who develops or have worsening dyspnea, pericardial effusion and pericardial tamponade should be considered in differential diagnosis.


Assuntos
Tamponamento Cardíaco/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Betacoronavirus , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/patologia , Feminino , Coração/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pessoa de Meia-Idade , Miocárdio/patologia , Pandemias
8.
Braz J Cardiovasc Surg ; 35(4): 530-538, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32864934

RESUMO

In December 2019, a striking appearance of new cases of viral pneumonia in Wuhan led to the detection of a novel coronavirus (SARS-CoV2). By analyzing patients with severe manifestations, it became apparent that 20 to 35% of patients who died had preexisting cardiovascular disease. This finding warrants the important need to discuss the influence of SARS-CoV2 infection on the cardiovascular system and hemodynamics in the context of clinical management, particularly during mechanical ventilation. The SARS-CoV2 enters human cells through the spike protein binding to angiotensin-converting enzyme 2 (ACE2), which is important to cardiovascular modulation and endothelial signaling. As ACE2 is highly expressed in lung tissue, patients have been progressing to acute respiratory injury at an alarming frequency during the Coronavirus Disease (COVID-19) pandemic. Moreover, COVID-19 leads to high D-dimer levels and prothrombin time, which indicates a substantial coagulation disorder. It seems that an overwhelming inflammatory and thrombogenic condition is responsible for a mismatching of ventilation and perfusion, with a somewhat near-normal static lung compliance, which describes two types of pulmonary conditions. As such, positive pressure during invasive mechanical ventilation (IMV) must be applied with caution. The authors of this review appeal to the necessity of paying closer attention to assess microhemodynamic repercussion, by monitoring central venous oxygen saturation during strategies of IMV. It is well known that a severe respiratory infection and a scattered inflammatory process can cause non-ischemic myocardial injury, including progression to myocarditis. Early strategies that guide clinical decisions can be lifesaving and prevent extended myocardial damage. Moreover, cardiopulmonary failure refractory to standard treatment may necessitate the use of extreme therapeutic strategies, such as extracorporeal membrane oxygenation.


Assuntos
Sistema Cardiovascular/virologia , Infecções por Coronavirus/complicações , Hemodinâmica , Pneumonia Viral/complicações , Betacoronavirus , Sistema Cardiovascular/fisiopatologia , Humanos , Miocárdio/patologia , Pandemias , Respiração Artificial
9.
J Cardiovasc Magn Reson ; 22(1): 69, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32951605

RESUMO

PURPOSE: Common types of congenital heart disease exhibit a variety of structural and functional variations which may be accompanied by changes in the myocardial microstructure. We aimed to compare myocardial architecture from magnetic resonance diffusion tensor imaging (DTI) in preserved pathology specimens. MATERIALS AND METHODS: Pathology specimens (n = 24) formalin-fixed for 40.8 ± 7.9 years comprised tetralogy of Fallot (TOF, n = 10), dextro-transposition of great arteries (D-TGA, n = 8) five with ventricular septal defect (VSD), systemic right ventricle (n = 4), situs inversus totalis (SIT, n = 1) and levo-TGA (L-TGA, n = 1). Specimens were imaged using a custom spin-echo sequence and segmented automatically according to tissue volume fraction. In each specimen T1, T2, fractional anisotropy, mean diffusivity, helix angle (HA) and sheet angle (E2A) were quantified. Pathologies were compared according to their HA gradient, HA asymmetry and E2A mean value in each myocardial segment (anterior, posterior, septal and lateral walls). RESULTS: TOF and D-TGA with VSD had decreased helix angle gradient by - 0.34°/% and remained symmetric in the septum in comparison to D-TGA without VSD. Helix angle range was decreased by 45°. It was associated with a decreased HA gradient in the right ventricular (RV) wall, i.e. predominant circumferential myocytes. The sheet angle in the septum of TOF was opposing those of the left ventricular (LV) free wall. Univentricular systemic RV had the lowest HA gradient (- 0.43°/%) and the highest HA asymmetry (75%). HA in SIT was linear, asymmetric, and reversed with a sign change at about 70% of the depth at mid-ventricle. In L-TGA with VSD, HA was asymmetric (90%) and its gradients were decreased in the septum, anterior and lateral wall. CONCLUSION: The organization of the myocytes as determined by DTI differs between TOF, D-TGA, L-TGA, systemic RV and SIT specimens. These differences in cardiac structure may further enlighten our understanding of cardiac function in these diverse congenital heart diseases.


Assuntos
Imagem de Difusão por Ressonância Magnética , Ventrículos do Coração/diagnóstico por imagem , Miocárdio/patologia , Tetralogia de Fallot/diagnóstico por imagem , Adulto , Feminino , Ventrículos do Coração/anormalidades , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tetralogia de Fallot/patologia , Tetralogia de Fallot/fisiopatologia , Função Ventricular Esquerda , Função Ventricular Direita
10.
Br J Sports Med ; 54(19): 1157-1161, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32878870

RESUMO

SARS-CoV-2 is the causative virus responsible for the COVID-19 pandemic. This pandemic has necessitated that all professional and elite sport is either suspended, postponed or cancelled altogether to minimise the risk of viral spread. As infection rates drop and quarantine restrictions are lifted, the question how athletes can safely resume competitive sport is being asked. Given the rapidly evolving knowledge base about the virus and changing governmental and public health recommendations, a precise answer to this question is fraught with complexity and nuance. Without robust data to inform policy, return-to-play (RTP) decisions are especially difficult for elite athletes on the suspicion that the COVID-19 virus could result in significant cardiorespiratory compromise in a minority of afflicted athletes. There are now consistent reports of athletes reporting persistent and residual symptoms many weeks to months after initial COVID-19 infection. These symptoms include cough, tachycardia and extreme fatigue. To support safe RTP, we provide sport and exercise medicine physicians with practical recommendations on how to exclude cardiorespiratory complications of COVID-19 in elite athletes who place high demand on their cardiorespiratory system. As new evidence emerges, guidance for a safe RTP should be updated.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Miocardite/diagnóstico , Pneumonia Viral/complicações , Guias de Prática Clínica como Assunto , Transtornos Respiratórios/diagnóstico , Volta ao Esporte/normas , Atletas , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Humanos , Miocardite/sangue , Miocardite/etiologia , Miocárdio/patologia , Necrose/etiologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Transtornos Respiratórios/etiologia , Medicina Esportiva/normas , Avaliação de Sintomas , Troponina/sangue
11.
Biomed Environ Sci ; 33(8): 603-613, 2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32933612

RESUMO

Objective: To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment. Methods: One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm 2 for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca 2+, glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy. Results: The results showed that the 5, 10, and 30 mW/cm 2 shortwave radiation caused a significant increased in the levels of Ca 2+, AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation. Conclusion: Shortwave radiation of 5, 10, and 30 mW/cm 2 can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm 2 induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.


Assuntos
Cardiopatias/patologia , Coração/efeitos da radiação , Miocárdio/patologia , Ondas de Rádio/efeitos adversos , Animais , Relação Dose-Resposta à Radiação , Cardiopatias/etnologia , Cardiopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
12.
J Toxicol Sci ; 45(9): 549-558, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879254

RESUMO

Trimethyltin chloride (TMT) is a stabilizer by-product in the process of manufacturing plastic, which is a kind of very strong toxic substance, and has acute, cumulative and chronic toxicity. TMT may cause bradycardia in patients with occupational poisoning, the mechanism of which has not been reported. This study explored the mechanism of TMT resulting in bradycardia of C57BL/6 mice. TMT was administered to mice to measure heart rate, serum succinate dehydrogenase (SDH) level, and myocardial Na+/K+-ATPase activity and expression. The effects of TMT on myocardial apoptosis were observed by changing the expressions of caspase-3, Bax and Bcl-2 in myocardium. It was found that the heart rate and SDH activity in serum of mice gradually decreased with the increase of TMT dose compared with the control group. The activity and the expression of Na+/K+-ATPase in the heart tissue of mice exposed to TMT was measured and gradually decreased with the increase of dose and time. We measured the expression of Bcl-2, Bax, caspase-3 and cleaved caspase-3 in the heart tissues of TMT exposed mice and found that the expressions of Bax, caspase-3 and cleaved caspase-3 increased and the expressions of Bcl-2 decreased in the heart tissues of the TMT-exposed mice at different doses. With the extension of TMT exposure time, the expression of Bax and caspase-3 increased and the expression of Bcl-2 decreased in the heart tissues of TMT exposed mice. Our findings suggest the mechanisms of TMT resulting in bradycardia may be associated with the inhibited activity and decreased content of Na+/K+-ATPase, thus further leading to the changes of Bcl-2, Bax, caspase-3 and cleaved caspase-3 in the mice's ventricular tissues.


Assuntos
Apoptose/efeitos dos fármacos , Bradicardia/etiologia , Miocárdio/metabolismo , Miocárdio/patologia , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Compostos de Trimetilestanho/toxicidade , Animais , Apoptose/genética , Bradicardia/genética , Caspase 3/genética , Caspase 3/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
14.
Ann Hematol ; 99(11): 2507-2512, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32918595

RESUMO

Iron overload comprises one of the main complications of congenital dyserythropoietic anemia type I (CDA-I). When analyzing magnetic resonance imaging T2* (MRI T2*) results in CDA patients, two previous studies reported discordant results regarding iron load in these patients. To further understand iron loading pattern in this group of patients, we analyzed MRI T2* findings in 46 CDA-I patients. Mild to moderate hepatic iron overload was detected in 28/46 (60.8%) patients. A significant correlation was found between serum ferritin and liver iron concentration (LIC). A significant correlation (p value = 0.02) was also found between the patient's age and LIC, reflecting increased iron loading over time, even in the absence of transfusion therapy. Notably, no cardiac iron overload was detected in any patient. Transfusion-naive patients had better LIC and better cardiac T2* values. These results demonstrate that a high percentage of CDA-I patients have liver iron concentration above the normal values, risking them with significant morbidity and mortality, and emphasize the importance of periodic MRI T2* studies for direct assessment of tissue iron concentration in these patients, taking age and transfusional burden into consideration.


Assuntos
Anemia Diseritropoética Congênita , Sobrecarga de Ferro , Ferro/sangue , Fígado , Imagem por Ressonância Magnética , Miocárdio/metabolismo , Adolescente , Adulto , Anemia Diseritropoética Congênita/sangue , Anemia Diseritropoética Congênita/diagnóstico por imagem , Criança , Pré-Escolar , Ferritinas/sangue , Seguimentos , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Int Heart J ; 61(5): 1070-1074, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921673

RESUMO

We report a case of lethal myocarditis and myositis after pembrolizumab treatment for advanced upper urinary tract urothelial carcinoma. A 69-year-old man underwent pembrolizumab therapy as a second-line treatment. He had myalgia and a slightly elevated creatinine kinase (CK) on the day of the second administration of pembrolizumab. Five days later, the patient was admitted with severe fatigue and an abnormal gait. Physical examination revealed reduced muscle reflexes and proximal muscle weakness. An electrocardiogram (ECG) demonstrated a wide QRS complex ventricular rhythm. A marked elevation of cardiac enzymes, including CK, myoglobin, and cardiac troponin I, was detected. Myocardial biopsy revealed inflammatory cell infiltration and the partial impairment of myocardial tissue. The electromyogram was normal, but inflammation in myofibers was noted in a muscle biopsy. Myocarditis and myositis as immune-related adverse events (irAEs) were suspected, and the patient began intravenous steroid therapy and plasma exchange. However, the patient underwent cardiac arrest three days after admission and began extracorporeal membrane oxygenation and intra-aortic balloon pumping therapy. Despite steroid pulse therapy, the patient demonstrated no sign of improvement and subsequently died 17 days after admission. Immune-mediated myocarditis is a rare but fatal irAE of an immune checkpoint inhibitor (ICI). The present case suggests that myositis precedes myocarditis. Therefore, if myositis is suspected, subsequent myocarditis may need attention. In conclusion, we found that myositis and myocarditis developed in a patient with advanced urothelial carcinoma after pembrolizumab treatment. A routine follow-up of CK and cardiac troponin I, as well as an ECG, should be performed to identify any possible ICI-induced myocarditis and myositis quickly.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Miocardite/induzido quimicamente , Miosite/induzido quimicamente , Idoso , Carcinoma de Células de Transição/secundário , Creatina Quinase/sangue , Creatina Quinase Forma MB/sangue , Ecocardiografia , Eletromiografia , Oxigenação por Membrana Extracorpórea , Evolução Fatal , Glucocorticoides/uso terapêutico , Parada Cardíaca , Humanos , Balão Intra-Aórtico , Pelve Renal , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Músculo Esquelético/patologia , Miocardite/sangue , Miocardite/diagnóstico por imagem , Miocardite/patologia , Miocárdio/patologia , Mioglobina/sangue , Miosite/sangue , Miosite/patologia , Miosite/fisiopatologia , Troca Plasmática , Troponina I/sangue
16.
PLoS Biol ; 18(9): e3000848, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898131

RESUMO

Improper lengths of actin-thin filaments are associated with altered contractile activity and lethal myopathies. Leiomodin, a member of the tropomodulin family of proteins, is critical in thin filament assembly and maintenance; however, its role is under dispute. Using nuclear magnetic resonance data and molecular dynamics simulations, we generated the first atomic structural model of the binding interface between the tropomyosin-binding site of cardiac leiomodin and the N-terminus of striated muscle tropomyosin. Our structural data indicate that the leiomodin/tropomyosin complex only forms at the pointed end of thin filaments, where the tropomyosin N-terminus is not blocked by an adjacent tropomyosin protomer. This discovery provides evidence supporting the debated mechanism where leiomodin and tropomodulin regulate thin filament lengths by competing for thin filament binding. Data from experiments performed in cardiomyocytes provide additional support for the competition model; specifically, expression of a leiomodin mutant that is unable to interact with tropomyosin fails to displace tropomodulin at thin filament pointed ends and fails to elongate thin filaments. Together with previous structural and biochemical data, we now propose a molecular mechanism of actin polymerization at the pointed end in the presence of bound leiomodin. In the proposed model, the N-terminal actin-binding site of leiomodin can act as a "swinging gate" allowing limited actin polymerization, thus making leiomodin a leaky pointed-end cap. Results presented in this work answer long-standing questions about the role of leiomodin in thin filament length regulation and maintenance.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Proteínas de Capeamento de Actina/química , Proteínas de Capeamento de Actina/metabolismo , Citoesqueleto de Actina/química , Actinas/química , Actinas/metabolismo , Animais , Animais Recém-Nascidos , Sítios de Ligação , Células Cultivadas , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/metabolismo , Humanos , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Miocárdio/metabolismo , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Ratos , Sarcômeros/metabolismo
17.
PLoS One ; 15(9): e0237810, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936824

RESUMO

Cardiovascular diseases are a leading cause of death worldwide. After an ischemic injury, the myocardium undergoes severe necrosis and apoptosis, leading to a dramatic degradation of function. Numerous studies have reported that cardiac fibroblasts (CFs) play a critical role in heart function even after injury. However, CFs present heterogeneous characteristics according to their development stage (i.e., fetal or adult), and the molecular mechanisms by which they maintain heart function are not fully understood. The aim of this study is to explore the hypothesis that a specific population of CFs can repair the injured myocardium in heart failure following ischemic infarction, and lead to a significant recovery of cardiac function. Flow cytometry analysis of CFs defined two subpopulations according to their relative expression of vascular cell adhesion molecule 1 (VCAM1). Whole-transcriptome analysis described distinct profiles for these groups, with a correlation between VCAM1 expression and lymphangiogenesis-related genes up-regulation. Vascular formation assays showed a significant stimulation of lymphatic cells network complexity by VCFs. Injection of human VCAM1-expressing CFs (VCFs) in postinfarct heart failure rat models (ligation of the left anterior descending artery) led to a significant restoration of the left ventricle contraction. Over the course of the experiment, left ventricular ejection fraction and fractional shortening increased by 16.65% ± 5.64% and 10.43% ± 6.02%, respectively, in VCF-treated rats. Histological examinations revealed that VCFs efficiently mobilized the lymphatic endothelial cells into the infarcted area. In conclusion, human CFs present heterogeneous expression of VCAM1 and lymphangiogenesis-promoting factors. VCFs restore the mechanical properties of ventricular walls by mobilizing lymphatic endothelial cells into the infarct when injected into a rat heart failure model. These results suggest a role of this specific population of CFs in the homeostasis of the lymphatic system in cardiac regeneration, providing new information for the study and therapy of cardiac diseases.


Assuntos
Fibroblastos/patologia , Insuficiência Cardíaca/fisiopatologia , Linfangiogênese , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Insuficiência Cardíaca/sangue , Humanos , Vasos Linfáticos/metabolismo , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Neovascularização Fisiológica , Ratos , Molécula 1 de Adesão de Célula Vascular/sangue
18.
Nat Commun ; 11(1): 4283, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883967

RESUMO

Our understanding of the spatiotemporal regulation of cardiogenesis is hindered by the difficulties in modeling this complex organ currently by in vitro models. Here we develop a method to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies. Consecutive morphological changes proceed in a self-organizing manner in the presence of the laminin-entactin (LN/ET) complex and fibroblast growth factor 4 (FGF4), and the resulting in vitro heart organoid possesses atrium- and ventricle-like parts containing cardiac muscle, conducting tissues, smooth muscle and endothelial cells that exhibited myocardial contraction and action potentials. The heart organoids exhibit ultrastructural, histochemical and gene expression characteristics of considerable similarity to those of developmental hearts in vivo. Our results demonstrate that this method not only provides a biomimetic model of the developing heart-like structure with simplified differentiation protocol, but also represents a promising research tool with a broad range of applications, including drug testing.


Assuntos
Matriz Extracelular/metabolismo , Fator 4 de Crescimento de Fibroblastos/metabolismo , Coração , Células-Tronco Embrionárias Murinas/metabolismo , Organoides , Potenciais de Ação , Diamino Aminoácidos/metabolismo , Animais , Biomimética/métodos , Diferenciação Celular , Linhagem Celular , Células Endoteliais , Coração/crescimento & desenvolvimento , Coração/fisiologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Contração Miocárdica , Miocárdio , Organoides/citologia , Organoides/crescimento & desenvolvimento , Organoides/ultraestrutura
19.
J Cardiovasc Magn Reson ; 22(1): 62, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32878630

RESUMO

BACKGROUND: Intensive endurance exercise may induce a broad spectrum of right ventricular (RV) adaptation/remodelling patterns. Late gadolinium enhancement (LGE) has also been described in cardiovascular magnetic resonance (CMR) of some endurance athletes and its clinical meaning remains controversial. Our aim was to characterize the features of contrast CMR and the observed patterns of the LGE distribution in a cohort of highly trained endurance athletes. METHODS: Ninety-three highly trained endurance athletes (> 12 h training/week at least during the last 5 years; 36 ± 6 years old; 53% male) and 72 age and gender-matched controls underwent a resting contrast CMR. In a subgroup of 28 athletes, T1 mapping was also performed. RESULTS: High endurance training load was associated with larger bi-ventricular and bi-atrial sizes and a slight reduction of biventricular ejection fraction, as compared to controls in both genders (p < 0.05). Focal LGE was significantly more prevalent in athletes than in healthy subjects (37.6% vs 2.8%; p < 0.001), with a typical pattern in the RV insertion points. In T1 mapping, those athletes who had focal LGE had higher extracellular volume (ECV) at the remote myocardium than those without (27 ± 2.2% vs 25.2 ± 2.1%; p < 0.05). CONCLUSIONS: Highly trained endurance athletes showed a ten-fold increase in the prevalence of focal LGE as compared to control subjects, always confined to the hinge points. Additionally, those athletes with focal LGE demonstrated globally higher myocardial ECV values. This matrix remodelling and potential presence of myocardial fibrosis may be another feature of the athlete's heart, of which the clinical and prognostic significance remains to be determined.


Assuntos
Atletas , Cardiomegalia Induzida por Exercícios , Meios de Contraste/administração & dosagem , Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Compostos Organometálicos/administração & dosagem , Resistência Física , Função Ventricular Direita , Remodelação Ventricular , Adaptação Fisiológica , Adulto , Estudos de Casos e Controles , Feminino , Fibrose , Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Adulto Jovem
20.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(8): 953-959, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32912409

RESUMO

OBJECTIVE: To prepare primary cardiomyocyte (PCM) specific peptide-conjugated mesoporous silicon nanoparticles (MSN) with L-arginine (LA) as a core (PCM-MSN@LA), and evaluate its specific protective effect on septic myocardium. METHODS: PCM-MSN@LA was prepared by condensation reaction, the characterization of PCM-MSN@LA, the amount of LA modification and release was detected, and the phagocytosis of PCM-MSN@LA and its affinity to myocardial tissue was observed. (1) Experiment one: SD neonatal rat cardiomyocytes were divided into control group (Con group), lipopolysaccharide (LPS) group, MSN@LA/LPS group and PCM-MSN@LA/LPS group. The LPS group was stimulated with 5 mg/L LPS for 16 hours, while the MSN@LA/LPS group and PCM-MSN@LA/LPS group were treated with 5 mg/L LPS and 25 mg/L LA-containing nanoparticles (MSN@LA and PCM-MSN@LA) for 16 hours. Cell viability and reactive oxygen species (ROS) production levels were detected. Apoptosis was observed via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method (TUNEL). Western Blot was used to detect the changes in endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) proteins. (2) Experiment two: 64 healthy male C57BL/6 mice were divided into Sham group, LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group by random number table method, 16 mice in each group. LPS group were injected 50 mg/kg LPS intraperitoneally. MSN@LA/LPS group and PCM-MSN@LA/LPS group were injected with 0.5 mg/kg MSN@LA and PCM-MSN@LA via tail vein immediately after intraperitoneal injection of LPS. Eight animals in each group were used to observe the 24-hour survival rate, and the other 8 mice were used to detect cardiac function by echocardiography at 12 hours after operation; mRNA expressions of interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) were measured by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). RESULTS: PCM-MSN@LA was spherical, with particle size of about 180 nm, Zeta potential of about -21 mV, with LA loaded. The amount of LA modification and release rate were 12.3% and 24.3%, respectively. Cell phagocytosis experiments showed that PCM-MSN@LA had the targeting ability of cardiomyocytes and myocardial tissue. Experiment one: after LPS stimulation of myocardial cells, cell viability decreased, while ROS generation, apoptosis, eNOS and iNOS protein expressions increased. Compared with LPS group, MSN@LA/LPS group and PCM-MSN@LA/LPS group had higher cell viability, reduced ROS levels and apoptosis, increased expressions of eNOS and iNOS. PCM-MSN@LA/LPS group changed the above effect further than MSN@LA/LPS group [cell viability (A value): 0.51±0.08 vs. 0.41±0.03, ROS (relative fluorescence intensity): 28 450±1 941 vs. 35 628±2 551, TUNEL positive cells/total cells: 0.27±0.03 vs. 0.35±0.04, eNOS/ß-Tubulin: 1.467±0.046 vs. 1.201±0.131, iNOS/ß-Tubulin: 1.700±0.033 vs. 1.577±0.068, all P < 0.05]. Experiment two: the number of 24-hour survive in MSN@LA/LPS group and PCM-MSN@LA/LPS group were higher than LPS group (number: 2, 4 vs. 1, P values were 0.36 and 0.03 respectively). Compared with Sham group, the cardiac function of LPS group was significantly inhibited and the mRNA expression of inflammatory factors increased. The PCM-MSN@LA/LPS group had higher left ventricular ejection fraction (LVEF) and left ventricular short-axis shortening rate (LVFS) than LPS group, and lower mRNA expressions of IL-1, IL-6, and TNF-α mRNA [LVEF: 0.456±0.019 vs. 0.337±0.017, LVFS: (21.97±1.78)% vs. (15.53±1.67)%, IL-1 mRNA (2-ΔΔCT): 169.22±8.95 vs. 189.79±6.79, IL-6 mRNA (2-ΔΔCT): 19.90±1.60 vs. 23.74±1.45, TNF-α mRNA (2-ΔΔCT): 8.21±0.81 vs. 11.00±1.48, all P < 0.05]. There was no significant difference in each index between the MSN@LA/LPS group and LPS group. CONCLUSIONS: PCM-MSN@LA with myocardial targeting characteristic significantly increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis, and achieved the targeted treatment of myocardial injury in sepsis.


Assuntos
Nanopartículas , Substâncias Protetoras , Sepse , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio , Ratos , Volume Sistólico , Função Ventricular Esquerda
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