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1.
BMC Cardiovasc Disord ; 20(1): 415, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928149

RESUMO

BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.


Assuntos
Bloqueio Atrioventricular/induzido quimicamente , Cegueira/induzido quimicamente , Transtornos da Consciência/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Metanol/envenenamento , Infarto do Miocárdio/induzido quimicamente , Solventes/envenenamento , Taquicardia Sinusal/induzido quimicamente , Adolescente , Adulto , Idoso , Bebidas Alcoólicas , Bloqueio Atrioventricular/sangue , Bloqueio Atrioventricular/fisiopatologia , Betacoronavirus , Cegueira/sangue , Cegueira/fisiopatologia , Gasometria , Síndrome de Brugada/sangue , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/fisiopatologia , Transtornos da Consciência/sangue , Transtornos da Consciência/fisiopatologia , Infecções por Coronavirus , Eletrocardiografia , Feminino , Contaminação de Alimentos , Humanos , Concentração de Íons de Hidrogênio , Irã (Geográfico) , Síndrome do QT Longo/sangue , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Pandemias , Pneumonia Viral , Envenenamento/sangue , Envenenamento/fisiopatologia , Fatores Sexuais , Taquicardia Sinusal/sangue , Taquicardia Sinusal/fisiopatologia , Adulto Jovem
2.
Nat Commun ; 11(1): 4416, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887881

RESUMO

Despite the clear association between myocardial injury, heart failure and depressed myocardial energetics, little is known about upstream signals responsible for remodeling myocardial metabolism after pathological stress. Here, we report increased mitochondrial calmodulin kinase II (CaMKII) activation and left ventricular dilation in mice one week after myocardial infarction (MI) surgery. By contrast, mice with genetic mitochondrial CaMKII inhibition are protected from left ventricular dilation and dysfunction after MI. Mice with myocardial and mitochondrial CaMKII overexpression (mtCaMKII) have severe dilated cardiomyopathy and decreased ATP that causes elevated cytoplasmic resting (diastolic) Ca2+ concentration and reduced mechanical performance. We map a metabolic pathway that rescues disease phenotypes in mtCaMKII mice, providing insights into physiological and pathological metabolic consequences of CaMKII signaling in mitochondria. Our findings suggest myocardial dilation, a disease phenotype lacking specific therapies, can be prevented by targeted replacement of mitochondrial creatine kinase or mitochondrial-targeted CaMKII inhibition.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomiopatia Dilatada/metabolismo , Infarto do Miocárdio/fisiopatologia , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Insuficiência Cardíaca/metabolismo , Ventrículos do Coração/fisiopatologia , Camundongos , Camundongos Transgênicos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Infarto do Miocárdio/cirurgia , Transdução de Sinais
3.
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
4.
PLoS One ; 15(8): e0237866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804979

RESUMO

Bedrest and immobilization following a myocardial infarction (MI) can lead to functional impairment that can persist following hospitalization. Early mobilization (EM) is associated with good functional and clinical outcomes in critical care, medical and surgical settings. However, the impact and current role of EM in post-MI care has not been well-defined. Our objective was to assess the evidence for post-MI mobilization, define current post-MI mobilization practice, and understand perspectives of cardiovascular professionals toward mobilization. A scoping review related to "early mobilization" and "myocardial infarction" was performed using the Joanna Briggs Institute Methodology. Pubmed, Embase, Google Scholar, Cochrane Library and CINAHL databases were included. Results were categorized into six topic areas. There were 59 references included in the analysis. There was evidence for the effectiveness and safety of earlier mobilization in experimental studies of the pre-revascularization era, but there was a lack of strong evidence for EM in contemporary post-MI care. Mobilization appears to be safe following arterial catheterization and is associated with minimal hemodynamic and respiratory compromise. Most people are delayed in mobilizing post-MI and spend the majority of the initial hospitalization period lying in bed. Only 1 of 7 current major cardiovascular professional societies guidelines recommend EM post-MI. There were no studies exploring the perspectives of cardiovascular professionals toward mobilization. EM may be beneficial in the post-MI care. However, there is an evidence gap for the impact of EM post-MI in the contemporary literature. More robust evidence from randomized clinical trials is required to inform clinicians and influence practice.


Assuntos
Deambulação Precoce , Infarto do Miocárdio/fisiopatologia , Atitude do Pessoal de Saúde , Hemodinâmica , Humanos , Guias de Prática Clínica como Assunto , Sociedades Médicas
5.
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
7.
Nat Commun ; 11(1): 3273, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601301

RESUMO

Restoration of coronary blood flow after a heart attack can cause reperfusion injury potentially leading to impaired cardiac function, adverse tissue remodeling and heart failure. Iron is an essential biometal that may have a pathologic role in this process. There is a clinical need for a precise noninvasive method to detect iron for risk stratification of patients and therapy evaluation. Here, we report that magnetic susceptibility imaging in a large animal model shows an infarct paramagnetic shift associated with duration of coronary artery occlusion and the presence of iron. Iron validation techniques used include histology, immunohistochemistry, spectrometry and spectroscopy. Further mRNA analysis shows upregulation of ferritin and heme oxygenase. While conventional imaging corroborates the findings of iron deposition, magnetic susceptibility imaging has improved sensitivity to iron and mitigates confounding factors such as edema and fibrosis. Myocardial infarction patients receiving reperfusion therapy show magnetic susceptibility changes associated with hypokinetic myocardial wall motion and microvascular obstruction, demonstrating potential for clinical translation.


Assuntos
Ferro/análise , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Idoso , Animais , Estudos Transversais , Feminino , Ferritinas/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/patologia , Cicatrização
8.
Am J Physiol Heart Circ Physiol ; 319(2): H443-H455, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618511

RESUMO

Neuregulin-1 (NRG1) is a paracrine growth factor, secreted by cardiac endothelial cells (ECs) in conditions of cardiac overload/injury. The current concept is that the cardiac effects of NRG1 are mediated by activation of erythroblastic leukemia viral oncogene homolog (ERBB)4/ERBB2 receptors on cardiomyocytes. However, recent studies have shown that paracrine effects of NRG1 on fibroblasts and macrophages are equally important. Here, we hypothesize that NRG1 autocrine signaling plays a role in cardiac remodeling. We generated EC-specific Erbb4 knockout mice to eliminate endothelial autocrine ERBB4 signaling without affecting paracrine NRG1/ERBB4 signaling in the heart. We first observed no basal cardiac phenotype in these mice up to 32 wk. We next studied these mice following transverse aortic constriction (TAC), exposure to angiotensin II (ANG II), or myocardial infarction in terms of cardiac performance, myocardial hypertrophy, myocardial fibrosis, and capillary density. In general, no major differences between EC-specific Erbb4 knockout mice and control littermates were observed. However, 8 wk following TAC both myocardial hypertrophy and fibrosis were attenuated by EC-specific Erbb4 deletion, albeit these responses were normalized after 20 wk. Similarly, 4 wk after ANG II treatment, myocardial fibrosis was less pronounced compared with control littermates. These observations were supported by RNA-sequencing experiments on cultured endothelial cells showing that NRG1 controls the expression of various hypertrophic and fibrotic pathways. Overall, this study shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling. This study contributes to understanding the spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury.NEW & NOTEWORTHY The role of NRG1/ERBB signaling in endothelial cells is not completely understood. Our study contributes to the understanding of spatiotemporal heterogeneity of myocardial autocrine and paracrine responses following cardiac injury and shows a role of endothelial autocrine NRG1/ERBB4 signaling in the modulation of hypertrophic and fibrotic responses during early cardiac remodeling.


Assuntos
Comunicação Autócrina , Cardiomiopatias/metabolismo , Células Endoteliais/metabolismo , Hipertrofia Ventricular Esquerda/metabolismo , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Neuregulina-1/metabolismo , Receptor ErbB-4/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Cardiomiopatias/genética , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Fibrose , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/genética , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Neovascularização Fisiológica , Comunicação Parácrina , Receptor ErbB-4/deficiência , Receptor ErbB-4/genética , Transdução de Sinais
9.
J Vis Exp ; (159)2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32510509

RESUMO

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


Assuntos
Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Infarto do Miocárdio/complicações , Transplante de Células-Tronco , Células-Tronco/citologia , Animais , Arritmias Cardíacas/fisiopatologia , Sobrevivência Celular , Modelos Animais de Doenças , Ecocardiografia , Estimulação Elétrica , Coração/fisiopatologia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Suínos , Função Ventricular Esquerda , Remodelação Ventricular
10.
J Biol Regul Homeost Agents ; 34(2): 367-378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32515175

RESUMO

To study changes in the sonic hedgehog (Shh) signaling pathway in acute myocardial infarction (AMI) and the protective effect of changes in Shh signaling pathway activity on AMI, specific pathogen-free (SPF) C57BL/6 mice were treated with left anterior descending (LAD) ligation to establish an AMI model. The samples were collected on the 1st, 3rd, 14th, and 21st days after AMI induction. After the operations, the mice were administered the Shh signaling pathway receptor agonist SAG1.3 (5 mg/kg/d) and antagonist SANT-1 (3.3 mg/kg/d) by intraperitoneal injection. The myocardial ischemia model was established by oxygen glucose deprivation (OGD) in vitro. The AMI mouse model and the in vitro OGD-induced myocardial ischemia model were established. The Smo agonist SAG1.3 was used to activate the Shh signaling pathway, thereby reducing the expression of Bcl-2 and Bax. The number of apoptotic cells was reduced. Administration of the antagonist SANT-1 inhibited Shh signaling pathway activity by increasing the expression of Bcl-2 and Bax, and the number of apoptotic cells increased. In conclusion, activation of the Shh signaling pathway improved cardiac functions and myocardial remodeling and reduced the apoptosis of myocardial cells.


Assuntos
Proteínas Hedgehog/fisiologia , Infarto do Miocárdio/fisiopatologia , Transdução de Sinais , Animais , Apoptose , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio
11.
J Vis Exp ; (160)2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32597875

RESUMO

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily and highly reproducible MI induction procedure is required to obtain further insight and better understanding of the underlying pathological changes. This procedure can also be used to evaluate the effects or potency of new and promising treatments (as drugs or interventions) in acute MI, subsequent remodeling and heart failure (HF). After intubation and pre-operative preparation of the animal, an anesthetic protocol with isoflurane was performed, and the surgical procedure was conducted quickly. Using a minimally invasive approach, the left anterior descending artery (LAD) was located and occluded by a ligature. The occlusion can be performed acutely for subsequent reperfusion (ischemia/reperfusion injury). Alternatively, the vessel can be ligated permanently to investigate the development of chronic MI, remodeling or HF. Despite common pitfalls, the drop-out rates are minimal. Various treatments such as remote ischemic conditioning can be examined for their cardioprotective potential pre-, peri- and post-operatively. The post-operative recovery was quick as the anesthesia was precisely controlled and the duration of the operation was short. Post-operative analgesia was administered for three days. The minimally invasive procedure reduces the risk of infection and inflammation. Furthermore, it facilitates rapid recovery. The "working heart" measurements were performed ex vivo and enabled precise control of preload, afterload and flow. This procedure requires specific equipment and training for adequate performance. This manuscript provides a detailed step-by-step introduction for conducting these measurements.


Assuntos
Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Anestesia , Animais , Cicatriz/patologia , Eletrocardiografia , Insuficiência Cardíaca , Hemodinâmica , Precondicionamento Isquêmico , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/cirurgia , Cuidados Pré-Operatórios , Ratos Sprague-Dawley , Remodelação Vascular , Função Ventricular
12.
J Cardiovasc Magn Reson ; 22(1): 34, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393281

RESUMO

BACKGROUND: The clinical application of cardiovascular magnetic resonance (CMR) T2 and T2* mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T2 and T2* mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated. METHODS: The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T2 or T2* values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data. RESULTS: One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T2 values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P <  0.01) compared with controls. T2 values in iron overload patients (SMD = - 0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T2* values were lower in patients with MI and iron overload (SMD of - 1.99 and - 2.39, respectively, P <  0.01) compared with controls. T2* values in HCM patients (SMD = - 0.61, P = 0.22), DCM patients (SMD = - 0.54, P = 0.06) and hypertension patients (SMD = - 1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies. CONCLUSIONS: The clinical utility of T2 and T2* mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T2 and T2* values of most cardiomyopathies are similar.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Transplante de Coração , Hipertensão/diagnóstico por imagem , Imagem por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Cardiomiopatias/epidemiologia , Cardiomiopatias/fisiopatologia , Diagnóstico Diferencial , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento
13.
PLoS One ; 15(5): e0232530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384091

RESUMO

BACKGROUND: Clinical and animal studies have found that anxiety and depression are significantly more common after acute myocardial infarction (AMI). The medial prefrontal cortex (PFC) has a dual role: in higher brain functions and in cardiovascular control, making it a logical candidate for explaining the perceived bidirectional heart-brain connection. We used parallel Electrocardiography (ECG) and Electrocorticography (ECoG) registration to investigate AMI-induced changes in medial PFC bioelectrical activity in a rat model of AMI. MATERIALS AND METHODS: Adult male Wistar albino rats were used in the study. Gold-plated recording electrodes were implanted over the frontal cortex for ECoG recording. ECG was recorded via two holter electrodes attached on the skin of the back fixed in place by a jacket. Induction of AMI was performed by isoprenaline (150 mg/kg, i.p.). ECoG and ECG signals were registered at baseline, during 3 hours after isoprenaline administration and at 24 hours after isoprenaline administration. RESULTS: Significant increases of theta, alpha, and beta electroencephalographic (EEG) band power were observed in different time intervals after isoprenaline administration. Significant increase of theta band peak frequency was also observed during the first hour after isoprenaline administration. No statistically significant differences in band-power activity were found between the pre-isoprenaline measurements and 24 hours after administration. CONCLUSION: Our results demonstrate significant increases in EEG band power of alpha beta and theta bands during isoprenaline-induced AMI model. These are the first findings to connect heart damage during isoprenaline- induced AMI to disturbances in the cortical bioelectrical activity.


Assuntos
Isoproterenol/farmacologia , Infarto do Miocárdio/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Ondas Encefálicas/fisiologia , Modelos Animais de Doenças , Eletrocardiografia , Eletrocorticografia , Eletroencefalografia , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos , Ratos Wistar
14.
Medicina (B Aires) ; 80(3): 253-270, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32442940

RESUMO

One in every four coronarographies performed to study myocardial ischemia shows coronary angiographic stenosis less than 50%. This data triggered an increasing interest in the medical community. The American Society of Cardiology recently published a position paper about the pathophysiology, diagnosis and treatment of this entity. Our group performed a narrative review reflecting the opinion of cardiology experts from different centers in Argentina. It aims physiopatologic and diagnostic aspect to understand the current approach in patients with MINOCA (myocardial infarction with non-obstructive coronary arteries) e INOCA (demonstrated angina and ischemia but without coronary lesions that justify this syndrome).


Assuntos
Tomada de Decisão Clínica , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Cineangiografia/métodos , Angiografia Coronária/métodos , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Prognóstico , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos
15.
Life Sci ; 256: 117811, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32422306

RESUMO

Acute myocardial infarction (AMI) is a major cardiovascular disease with high mortality worldwide. Hypoxia is a key inducing factor for AMI. We aimed to examine the expression and functions of Kcnq1ot1 (KCNQ1 overlapping transcript 1) in hypoxia-induced cardiomyocytes in the process of AMI. The left anterior descending coronary artery ligation (LAD) was used for inducing in-vivo AMI model and the primary cardiomyocytes were extracted; in-vitro H9c2 cell model was simulated by hypoxia treatment. TUNEL, flow cytometry and JC-1 assay were carried out to evaluate cell apoptosis. Mechanism assays including luciferase reporter assay and RIP assay revealed interplays between RNAs. To begin with, Kcnq1ot1 was revealed to be conspicuously upregulated in myocardium infracted zone and border zone within 2 days since establishment of the model. Moreover, inhibition of Kcnq1ot1 protected cardiomyocytes against hypoxia-triggered cell apoptosis during the process of AMI. Then, miR-466k and miR-466i-5p were proved to bind with Kcnq1ot1 and participated in Kcnq1ot1-mediated cardiomyocyte injury under hypoxia. Subsequently, Kcnq1ot1 was found to elevate Tead1 (TEA domain transcription factor 1) expression via sponging miR-466k and miR-466i-5p. Finally, it was verified that Kcnq1ot1 regulated hypoxia-induced cardiomyocyte injury dependent on Tead1. In conclusion, Kcnq1ot1 sponged miR-466k and miR-466i-5p to up-regulate Tead1, thus triggering cardiomyocyte injury in the process of AMI.


Assuntos
Apoptose/genética , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , RNA Longo não Codificante/genética , Animais , Modelos Animais de Doenças , Marcação In Situ das Extremidades Cortadas , Masculino , MicroRNAs/genética , Infarto do Miocárdio/genética , Ratos , Ratos Sprague-Dawley , Regulação para Cima
16.
Arch Biochem Biophys ; 690: 108430, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32473132

RESUMO

BACKGROUND: The severity and duration of hypoxia is known to determine apoptotic fate in heart; however, its implication during myocardial infarction (MI) remains unaddressed. Therefore the aim of the study was to determine apoptotic regulation in cardiomyocytes under varied hypoxic intensity and duration and to unravel the role of HIF-1α in such modulation. METHODS: Treatment of cardiomyocytes to varied hypoxic intensity and duration was carried out in vitro, which was mimicked in vivo by dose-dependent Isoproterenol hydrochloride treatment for varied time-points. Myocardium-targeted HIF-1α knockdown in vivo was performed to decipher its role in cardiomyocyte apoptosis under varied stress. Signaling intermediates were analyzed by RT-PCR, immunoblotting and co-immunoprecipitation. DCFDA-based ROS assay, Griess assay for NO release and biochemical assays for estimating caspase activity were performed. RESULTS: Severe stress resulted in cardiomyocyte apoptosis in both shorter and longer time-points. Moderate stress, on the other hand, induced apoptosis only in the shorter time-point which was downregulated in the longer time-point. ROS activity was upregulated under severe hypoxic stress for both time-points and only in the early time-point under moderate hypoxia. Increased ROS accumulation activated ERK-1/2 which stabilized nuclear HIF-1α, promoting bnip3-mediated apoptosis. Stable HSP90-IRE-1 association in such cells caused elevated endoplasmic reticulum stress-related caspase-12 activity. Sustained moderate hypoxia caused decline in ROS activity, but upregulated NFκB-dependent NO generation. NO-stabilized HIF-1α was predominantly cytosolic, since low ROS levels downregulated ERK-1/2 activity, thereby suppressing bnip3 expression. Cytosolic HIF-1α in such cells sequestered HSP90 from IRE-1, downregulating caspase-12 activity due to proteasomal degradation of IRE-1. Accordingly, myocardium-specific in vivo silencing of HIF-1α was beneficial at both time-points under severe stress as also for lesser duration of moderate stress. However, silencing of HIF-1α aggravated apoptotic injury during sustained moderate stress. CONCLUSION: ROS-mediated HIF-1α stabilization promotes cardiomyocyte apoptosis on one hand while NO-mediated stabilization of HIF-1α disrupts apoptosis depending upon the severity and duration of hypoxia. Therefore the outcome of modulation of cardiac HIF-1α activity is regulated by both the severity and duration of ischemic stress.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Infarto do Miocárdio/fisiopatologia , Animais , Apoptose , Caspase 12/metabolismo , Hipóxia Celular , Linhagem Celular , Estresse do Retículo Endoplasmático , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação da Expressão Gênica , Humanos , Mutação , Miócitos Cardíacos/citologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais , Fatores de Tempo , Transfecção
17.
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
18.
Nutr Metab Cardiovasc Dis ; 30(7): 1106-1114, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32448716

RESUMO

BACKGROUND AND AIMS: Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with a reduction of major cardiovascular events (MACE) and mortality on the basis of the results of cardiovascular outcome trials (CVOT). Several meta-analyses on this issue have been recently published; however, they were all restricted to CVOT, with the exclusion of all studies designed for other endpoints; moreover, other cardiovascular endpoints, such as atrial fibrillation and heart failure have not been fully explored. METHODS AND RESULTS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. We included 43 trials, enrolling 63,134 patients. A significant reduction of MACE (MH-OR 0.87 [0.83, 0.92]), all-cause mortality (MH-OR 0.89 [0.83, 0.96]), and a nonstatistical trend toward reduction of heart failure (MH-OR 0.93 [0.85, 1.01]) was observed - GLP1-RA did not increase the risk of atrial fibrillation (MH-OR 0.94 [0.84, 1.04]). CONCLUSION: The present meta-analysis confirms the favorable effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction. Conversely, the effects on heart failure remain uncertain. Available data on atrial fibrillation seems to exclude any major safety issues in this respect. REGISTRATION NUMBER (PROSPERO): CRD42018115577.


Assuntos
Fibrilação Atrial/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Insuficiência Cardíaca/prevenção & controle , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Incretinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
Adv Exp Med Biol ; 1177: 1-36, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32246442

RESUMO

In most developed countries, coronary artery disease (CAD), mostly caused by atherosclerosis of coronary arteries, is one of the primary causes of death. From 1990s to 2000s, mortality caused by acute MI declined up to 50%. The incidence of CAD is related with age, gender, economic, etc. Atherosclerosis contains some highly correlative processes such as lipid disturbances, thrombosis, inflammation, vascular smooth cell activation, remodeling, platelet activation, endothelial dysfunction, oxidative stress, altered matrix metabolism, and genetic factors. Risk factors of CAD exist among many individuals of the general population, which includes hypertension, lipids and lipoproteins metabolism disturbances, diabetes mellitus, chronic kidney disease, age, genders, lifestyle, cigarette smoking, diet, obesity, and family history. Angina pectoris is caused by myocardial ischemia in the main expression of pain in the chest or adjoining area, which is usually a result of exertion and related to myocardial function disorder. Typical angina pectoris would last for minutes with gradual exacerbation. Rest, sit, or stop walking are the usual preference for patients with angina, and reaching the maximum intensity in seconds is uncommon. Rest or nitroglycerin usage can relieve typical angina pectoris within minutes. So far, a widely accepted angina pectoris severity grading system included CCS (Canadian Cardiovascular Society) classification, Califf score, and Goldman scale. Patients with ST-segment elevated myocardial infarction (STEMI) may have different symptoms and signs of both severe angina pectoris and various complications. The combination of rising usage of sensitive MI biomarkers and precise imaging techniques, including electrocardiograph (ECG), computed tomography, and cardiac magnetic resonance imaging, made the new MI criteria necessary. Complications of acute myocardial infarction include left ventricular dysfunction, cardiogenic shock, structural complications, arrhythmia, recurrent chest discomfort, recurrent ischemia and infarction, pericardial effusion, pericarditis, post-myocardial infarction syndrome, venous thrombosis pulmonary embolism, left ventricular aneurysm, left ventricular thrombus, and arterial embolism.


Assuntos
Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Angina Pectoris/fisiopatologia , Angina Pectoris/terapia , Humanos , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/terapia
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