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1.
Physiol Rev ; 103(1): 391-432, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35953269

RESUMO

The heart is imbued with a vast lymphatic network that is responsible for fluid homeostasis and immune cell trafficking. Disturbances in the forces that regulate microvascular fluid movement can result in myocardial edema, which has profibrotic and proinflammatory consequences and contributes to cardiovascular dysfunction. This review explores the complex relationship between cardiac lymphatics, myocardial edema, and cardiac disease. It covers the revised paradigm of microvascular forces and fluid movement around the capillary as well as the arsenal of preclinical tools and animal models used to model myocardial edema and cardiac disease. Clinical studies of myocardial edema and their prognostic significance are examined in parallel to the recent elegant animal studies discerning the pathophysiological role and therapeutic potential of cardiac lymphatics in different cardiovascular disease models. This review highlights the outstanding questions of interest to both basic scientists and clinicians regarding the roles of cardiac lymphatics in health and disease.


Assuntos
Edema Cardíaco , Cardiopatias , Vasos Linfáticos , Animais , Modelos Animais de Doenças , Edema Cardíaco/fisiopatologia , Cardiopatias/fisiopatologia , Vasos Linfáticos/fisiopatologia
2.
Stud Health Technol Inform ; 295: 491-494, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35773918

RESUMO

This paper explores the capabilities of a sophisticated deep learning method, named Deep Time Growing Neural Network (DTGNN), and compares its possibilities against a generally well-known method, Convolutional Neural network (CNN). The comparison is performed by using time series of the heart sound signal, so-called Phonocardiography (PCG). The classification objective is to discriminate between healthy and patients with cardiac diseases by applying a deep machine learning method to PCGs. This approach which is called intelligent phonocardiography has received interest from the researchers toward the development of a smart stethoscope for decentralized diagnosis of heart disease. It is found that DTGNN associates further flexibility to the approach which enables the classifier to learn subtle contents of PCG, and meanwhile better copes with the complexities intrinsically that exist in the medical applications such as the imbalance training. The structural risk of the two methods is compared using the A-Test method.


Assuntos
Cardiopatias/diagnóstico , Ruídos Cardíacos , Redes Neurais de Computação , Fonocardiografia , Aprendizado Profundo , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Humanos
3.
J Electrocardiol ; 72: 44-48, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35306293

RESUMO

OBJECTIVE: The aim of this study is to examine the probability of de-novo fQRS in patients with mild COVID-19 disease, as an indicator of cardiac injury. METHODS: Data of 256 patients with normal admission electrocardiography and no comorbidities between 1.12.2020-31.12.2021, were examined retrospectively 6-month after mild COVID-19 disease. Patients were divided into two groups: fQRS+ group (n = 102) and non-fQRS group (n = 154). Relation between fQRS and other electrocardiography, echocardiographic and laboratory findings were investigated. RESULTS: No significant difference was found between the groups among age and gender. Troponin-I and creatine kinase myocardial band values (retrospectively 9.10 ± 1.76 vs 0.74 ± 1.43, 34.05 ± 82.20 vs. 14.68 ± 4.42), COVID-19 IgG levels (45.78 ± 14.82 vs. 36.49 ± 17.68), diastolic dysfunction (39.21% vs. 15.07%), EF value (58.02 ± 1.95 vs. 64.27 ± 3.07), dyspnea (41.17% vs. 6.84%), post-COVID-19 tachycardia syndrome (19.6% vs. 2.74) were more frequent in fQRS+ group compared to non-fQRS group. The EF value was lower in the presence of fQRS in the high lateral leads (57.12 ± 1.99, 58.47 ± 1.79, p:0.018). There was a positive correlation between IgG value and endsystolic diameter, septum thickness and left atrium diameter. In multivariate analysis de-novo fQRS, dyspnea, high troponin and IgG values, diastolic dysfunction, low EF value and left atrial diameter were determined as independent risk factors for post-COVID-19 tachycardia syndrome in follow-up. CONCLUSION: In COVID-19 disease de-novo fQRS, dyspnea, high IgG and troponin value, left atrial diameter, lower EF value, diastolic dysfunction were associated with post-COVID-19 tachycardia syndrome. The de-novo fQRS in SARS-COV-2 may be a predictor of future more important adverse cardiovascular outcomes and this should alert clinicians.


Assuntos
COVID-19 , Eletrocardiografia , Cardiopatias , COVID-19/complicações , COVID-19/fisiopatologia , Dispneia/fisiopatologia , Dispneia/virologia , Seguimentos , Cardiopatias/fisiopatologia , Cardiopatias/virologia , Humanos , Imunoglobulina G , Estudos Retrospectivos , SARS-CoV-2 , Troponina
6.
Cardiovasc Res ; 118(2): 424-439, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512477

RESUMO

The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.


Assuntos
Cardiopatias/enzimologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Miócitos Cardíacos/enzimologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Cardiopatias/diagnóstico , Cardiopatias/tratamento farmacológico , Cardiopatias/fisiopatologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores
7.
Cardiovasc Res ; 118(2): 531-541, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33605403

RESUMO

AIMS: The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. METHODS AND RESULTS: Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. CONCLUSION: Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.


Assuntos
Circulação Coronária , Vasos Coronários/fisiopatologia , Cardiopatias/fisiopatologia , Microcirculação , Microvasos/fisiopatologia , Animais , Antibióticos Antineoplásicos , Cardiotoxicidade , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Modelos Animais de Doenças , Doxorrubicina , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico por imagem , Cardiopatias/patologia , Imageamento por Ressonância Magnética , Masculino , Microvasos/diagnóstico por imagem , Microvasos/patologia , Imagem de Perfusão do Miocárdio , Sus scrofa , Fatores de Tempo
8.
Cardiovasc Res ; 118(2): 386-398, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33483740

RESUMO

Protein kinase A (PKA) is a central regulator of cardiac performance and morphology. Myocardial PKA activation is induced by a variety of hormones, neurotransmitters, and stress signals, most notably catecholamines secreted by the sympathetic nervous system. Catecholamines bind ß-adrenergic receptors to stimulate cAMP-dependent PKA activation in cardiomyocytes. Elevated PKA activity enhances Ca2+ cycling and increases cardiac muscle contractility. Dynamic control of PKA is essential for cardiac homeostasis, as dysregulation of PKA signalling is associated with a broad range of heart diseases. Specifically, abnormal PKA activation or inactivation contributes to the pathogenesis of myocardial ischaemia, hypertrophy, heart failure, as well as diabetic, takotsubo, or anthracycline cardiomyopathies. PKA may also determine sex-dependent differences in contractile function and heart disease predisposition. Here, we describe the recent advances regarding the roles of PKA in cardiac physiology and pathology, highlighting previous study limitations and future research directions. Moreover, we discuss the therapeutic strategies and molecular mechanisms associated with cardiac PKA biology. In summary, PKA could serve as a promising drug target for cardioprotection. Depending on disease types and mechanisms, therapeutic intervention may require either inhibition or activation of PKA. Therefore, specific PKA inhibitors or activators may represent valuable drug candidates for the treatment of heart diseases.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Cardiopatias/enzimologia , Contração Miocárdica , Miocárdio/enzimologia , Animais , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Ativação Enzimática , Cardiopatias/tratamento farmacológico , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Terapia de Alvo Molecular , Miocárdio/patologia , Fosforilação , Inibidores de Proteínas Quinases/uso terapêutico , Transdução de Sinais
9.
Cardiovasc Res ; 118(1): 130-140, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33188592

RESUMO

Cardiovascular (CV) stiffening represents a complex series of events evolving from pathological changes in individual cells of the vasculature and heart which leads to overt tissue fibrosis. While vascular stiffening occurs naturally with ageing it is accelerated in states of insulin (INS) resistance, such as obesity and type 2 diabetes. CV stiffening is clinically manifested as increased arterial pulse wave velocity and myocardial fibrosis-induced diastolic dysfunction. A key question that remains is how are these events mechanistically linked. In this regard, heightened activation of vascular mineralocorticoid receptors (MR) and hyperinsulinaemia occur in obesity and INS resistance states. Further, a downstream mediator of MR and INS receptor activation, the endothelial cell Na+ channel (EnNaC), has recently been identified as a key molecular determinant of endothelial dysfunction and CV fibrosis and stiffening. Increased activity of the EnNaC results in a number of negative consequences including stiffening of the cortical actin cytoskeleton in endothelial cells, impaired endothelial NO release, increased oxidative stress-meditated NO destruction, increased vascular permeability, and stimulation of an inflammatory environment. Such endothelial alterations impact vascular function and stiffening through regulation of vascular tone and stimulation of tissue remodelling including fibrosis. In the case of the heart, obesity and INS resistance are associated with coronary vascular endothelial stiffening and associated reductions in bioavailable NO leading to heart failure with preserved systolic function (HFpEF). After a brief discussion on mechanisms leading to vascular stiffness per se, this review then focuses on recent findings regarding the role of INS and aldosterone to enhance EnNaC activity and associated CV stiffness in obesity/INS resistance states. Finally, we discuss how coronary artery-mediated EnNaC activation may lead to cardiac fibrosis and HFpEF, a condition that is especially pronounced in obese and diabetic females.


Assuntos
Vasos Coronários/metabolismo , Células Endoteliais/metabolismo , Canais Epiteliais de Sódio/metabolismo , Cardiopatias/metabolismo , Miocárdio/metabolismo , Remodelação Vascular , Rigidez Vascular , Função Ventricular Esquerda , Remodelação Ventricular , Aldosterona/metabolismo , Circulação Coronária , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Células Endoteliais/patologia , Feminino , Fibrose , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Insulina/metabolismo , Masculino , Miocárdio/patologia , Receptores de Mineralocorticoides/metabolismo , Transdução de Sinais , Sódio/metabolismo
10.
Cardiol Rev ; 30(1): 38-43, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32991394

RESUMO

Systemic lupus erythematosus (SLE) is a complex connective tissue disease that can potentially affect every organ of the human body. In some cases, SLE may present with diverse cardiac manifestations including pericarditis, myocarditis, valvular disease, atherosclerosis, thrombosis, and arrhythmias. Heart disease in SLE is associated with increased morbidity and mortality. It is unclear whether traditional treatments for coronary artery disease significantly impact mortality in this population. Current therapeutic agents for SLE include glucocorticoids, hydroxychloroquine, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, and B cell-directed therapies. This article will provide a comprehensive review and update on this important disease state.


Assuntos
Cardiopatias , Lúpus Eritematoso Sistêmico , Cardiopatias/diagnóstico , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Humanos , Incidência , Lúpus Eritematoso Sistêmico/complicações , Fatores de Risco
11.
Sci Rep ; 11(1): 23576, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34880374

RESUMO

Acute sympathetic stress can result in cardiac fibrosis, but may also lead to mental dysfunction. Exercise training after isoproterenol (ISO)-induced acute sympathetic stress was investigated regarding cardiac damage, neuroinflammation, brain function and behavior. Male Wistar rats (12 months) received ISO or saline. One week later, treadmill running or control handling (sedentary) started. After 4 weeks, cognitive- and exploratory behavior were evaluated, and heart and brain tissues were analyzed regarding cardiac damage, hippocampal neuroinflammation and neuronal function. ISO did not affect cognitive performance nor hippocampal function. However, ISO reduced anxiety, coinciding with locally reduced microglia (processes) size in the hippocampus. Exercise in ISO rats reversed anxiety, did not affect microglia morphology, but increased brain function. Thus, exercise after ISO did not affect cardiac damage, cognition or hippocampal neuroinflammation, but normalized anxiety. Increased localized BDNF expression may indicate improved brain function.


Assuntos
Comportamento Exploratório/fisiologia , Cardiopatias/induzido quimicamente , Cardiopatias/fisiopatologia , Hipocampo/fisiopatologia , Isoproterenol/farmacologia , Condicionamento Físico Animal/fisiologia , Animais , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/fisiologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Cardiopatias/metabolismo , Hipocampo/metabolismo , Masculino , Microglia/metabolismo , Microglia/fisiologia , /fisiopatologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Wistar
12.
Front Endocrinol (Lausanne) ; 12: 760292, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858333

RESUMO

Introduction: Type 2 diabetes (T2D) is characterized by a metabolic disorder that elevates blood glucose concentration. Chronic hyperglycemia has been associated with several complications in patients with T2D, one of which is cardiac autonomic dysfunction that can be assessed from heart rate variability (HRV) and heart rate recovery (HRR) response, both associated with many aspects of health and fitness, including severe cardiovascular outcomes. Objective: To evaluate the effects of T2D on cardiac autonomic modulation by means of HRV and HRR measurements. Materials and Methods: This study has an observational with case-control characteristic and involved ninety-three middle-aged adults stratified into two groups (control group - CG, n = 34; diabetes group - DG, n = 59). After signing the free and informed consent form, the patients were submitted to the evaluation protocols, performed biochemical tests to confirm the diagnosis of T2D, collection of R-R intervals for HRV analysis and cardiopulmonary effort test to quantify HRR. Results: At rest, the DG showed a reduction in global HRV (SDNN= 19.31 ± 11.72 vs CG 43.09 ± 12.74, p < 0.0001), lower parasympathetic modulation (RMSSD= 20.49 ± 14.68 vs 52.41 ± 19.50, PNN50 = 4.76 ± 10.53 vs 31.24 ± 19.24, 2VD%= 19.97 ± 10.30 vs 28.81 ± 9.77, p < 0.0001 for both indices) and higher HRrest when compared to CG. After interruption of physical exercise, a slowed heart rate response was observed in the DG when compared to the CG. Finally, a simple linear regression showed that fasting glycemia was able to predict cardiac autonomic involvement in volunteers with T2D. Conclusion: Patients with T2D presented lower parasympathetic modulation at rest and slowed HRR after physical exercise, which may be associated with higher cardiovascular risks. The findings show the glycemic profile as an important predictor of impaired cardiac autonomic modulation.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Glicemia/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Jejum/fisiologia , Coração/fisiopatologia , Hiperglicemia/fisiopatologia , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Estudos de Casos e Controles , Exercício Físico/fisiologia , Cardiopatias/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Pessoa de Meia-Idade
13.
BMC Cardiovasc Disord ; 21(1): 620, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34963447

RESUMO

BACKGROUND: It is well established that body mass index (BMI) and troponins are independently associated. However, whether the obesity could cause myocardial injury independent of coronary heart disease (CHD) remains unclear. This study focuses on the relationship between BMI and troponins, and whether this relationship is being attenuated when CHD is accounted for. METHODS: In populations without acute ischemic events, 383 patients with coronary artery stenosis less than 75% were included, that is, people who have not yet reached the indications for coronary intervention, and of them 70 patients being obese according to BMI ≥ 28 kg/m2. Continuous variables were represented as mean ± SD or median(inter quartile range[IQR]). Chi-square test was adopted for categorical data. Correlations between variables were evaluated by Spearman analysis, multiple regression or logistic regression. RESULTS: The circulating hs-cTnT level was higher in the obese group [8(6,11) ng/L vs. 6(4,9) ng/L; p < 0.001). In subgroup analysis based on the presence or absence of coronary heart disease(CHD), the adjusted ß(95%CI) for circulating hs-cTnT exhibited a proportional relationship with BMI when the non-obesity were defined as the reference[ß; 2.22(95%CI, 0.73 to 3.71) in non-CHD, 5.58(95%CI, 0.70 to 10.46) in CHD, p < 0.05]. Additionally, the degree of coronary stenosis has shown a positive correlation with circulating hs-cTnT (rho = 0.1162; p < 0.05). CONCLUSION: When CHD is taken into account, obesity is independently associated to the elevation of circulating hs-cTnT, a biomarker of myocardial injury, potentially indicating the impact of obesity on non-ischemic subclinical myocardial injury.


Assuntos
Cardiopatias/etiologia , Obesidade/complicações , Troponina T/sangue , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Cardiopatias/sangue , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Regulação para Cima
14.
Int J Mol Sci ; 22(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34768996

RESUMO

Calcineurin, also known as protein phosphatase 2B, is a heterodimeric serine threonine phosphatase involved in numerous signaling pathways. During the past 50 years, calcineurin has been the subject of extensive investigation. Many of its cellular and physiological functions have been described, and the underlying biophysical mechanisms are the subject of active investigation. With the abundance of techniques and experimental designs utilized to study calcineurin and its numerous substrates, it is difficult to reconcile the available information. There have been a plethora of reports describing the role of calcineurin in cardiac disease. However, a physiological role of calcineurin in healthy cardiomyocyte function requires clarification. Here, we review the seminal biophysical and structural details that are responsible for the molecular function and inhibition of calcineurin. We then focus on literature describing the roles of calcineurin in cardiomyocyte physiology and disease.


Assuntos
Calcineurina/metabolismo , Cardiopatias/metabolismo , Coração/fisiologia , Animais , Biofísica/métodos , Cardiopatias/fisiopatologia , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Transdução de Sinais/fisiologia
16.
Anticancer Res ; 41(11): 5355-5364, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732405

RESUMO

Cardiotoxicity is a common side effect induced by cancer therapies, which increases the risk of long-term morbidity and mortality in cancer survivors. To date, the mechanism leading to this toxicity is still unclear, thus complicating cardiac safety assessment and predictive factor identification. The advances in technology, particularly regarding radiation therapy and constant development of novel antineoplastic agents, require urgent development of efficient preclinical models to detect drug cardiotoxicity. A myriad of empirical preclinical models have been used to investigate cardiotoxicity, though with limited success. Recently, multicellular spheroid models have gained attention by mimicking the in vivo microenvironment. The aim of this review is to focus on the most relevant preclinical models used to assess antineoplastic drug- and radiotherapy-related cardiotoxicities, with an overview on their current use. It also aims to discuss the possible directions of translational research in the cardio-oncology field.


Assuntos
Antineoplásicos , Cardiopatias/induzido quimicamente , Lesões por Radiação/etiologia , Animais , Técnicas Biossensoriais , Cardiotoxicidade , Linhagem Celular , Técnicas de Cocultura , Modelos Animais de Doenças , Cardiopatias/metabolismo , Cardiopatias/patologia , Cardiopatias/fisiopatologia , Humanos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Radioterapia , Fatores de Risco , Especificidade da Espécie , Microambiente Tumoral
17.
Circulation ; 144(17): 1429-1443, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34694887

RESUMO

Heart disease remains one of the greatest killers. In addition to genetics and traditional lifestyle risk factors, we now understand that adverse conditions during pregnancy can also increase susceptibility to cardiovascular disease in the offspring. Therefore, the mechanisms by which this occurs and possible preventative therapies are of significant contemporary interest to the cardiovascular community. A common suboptimal pregnancy condition is a sustained reduction in fetal oxygenation. Chronic fetal hypoxia results from any pregnancy with increased placental vascular resistance, such as in preeclampsia, placental infection, or maternal obesity. Chronic fetal hypoxia may also arise during pregnancy at high altitude or because of maternal respiratory disease. This article reviews the short- and long-term effects of hypoxia on the fetal cardiovascular system, and the importance of chronic fetal hypoxia in triggering a developmental origin of future heart disease in the adult progeny. The work summarizes evidence derived from human studies as well as from rodent, avian, and ovine models. There is a focus on the discovery of the molecular link between prenatal hypoxia, oxidative stress, and increased cardiovascular risk in adult offspring. Discussion of mitochondria-targeted antioxidant therapy offers potential targets for clinical intervention in human pregnancy complicated by chronic fetal hypoxia.


Assuntos
Hipóxia Celular/genética , Cardiopatias/fisiopatologia , Estresse Oxidativo/genética , Animais , Feminino , Humanos , Masculino
18.
Sci Rep ; 11(1): 20333, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645892

RESUMO

Levosimendan and dobutamine are extensively used to treat sepsis-associated cardiovascular failure in ICU. Nevertheless, the role and mechanism of levosimendan in patients with sepsis-induced cardiomyopathy remains unclear. Moreover, previous studies on whether levosimendan is superior to dobutamine are still controversial. More importantly, these studies did not take changes (before-after comparison to the baseline) in quantitative parameters such as ejection fraction into account with the baseline level. Here, we aimed to determine the pros and cons of the two medicines by assessing the changes in cardiac function and blood lactate, mortality, with the standardized mean difference used as a summary statistic. Relevant studies were obtained by a thorough and disciplined literature search in several notable academic databases, including Google Scholar, PubMed, Cochrane Library and Embase until November 2020. Outcomes included changes in cardiac function, lactic acid, mortality and length of hospital stay. A total of 6 randomized controlled trials were included in this study, including 192 patients. Compared with dobutamine, patients treated with levosimendan had a greater improvement of cardiac index (ΔCI) (random effects, SMD = 0.90 [0.20,1.60]; I2 = 76%, P < 0.01) and left ventricular stroke work index (ΔLVSWI) (random effects, SMD = 1.56 [0.90,2.21]; I2 = 65%, P = 0.04), a significant decrease of blood lactate (Δblood lactate) (random effects, MD = - 0.79 [- 1.33, - 0.25]; I2 = 68%, P < 0.01) at 24-h after drug intervention, respectively. There was no significant difference between levosimendan and dobutamine on all-cause mortality in ICU (fixed effect, OR = 0.72 [0.39,1.33]; I2 = 0%, P = 0.99). We combine effect sizes related to different measurement parameters to evaluate cardiac function, which implied that septic patients with myocardial dysfunction might have a better improvement of cardiac function by levosimendan than dobutamine (random effects, SMD = 1.05 [0.69,1.41]; I2 = 67%, P < 0.01). This study suggested a significant improvement of CI, LVSWI, and decrease of blood lactate in septic patients with myocardial dysfunction in ICU after 24-h administration of levosimendan than dobutamine. However, the administration of levosimendan has neither an impact on mortality nor LVEF. Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.


Assuntos
Dobutamina/uso terapêutico , Cardiopatias , Ácido Láctico/sangue , Sepse , Simendana/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Intervalo Livre de Doença , Cardiopatias/sangue , Cardiopatias/tratamento farmacológico , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Sepse/sangue , Sepse/tratamento farmacológico , Sepse/mortalidade , Sepse/fisiopatologia , Taxa de Sobrevida
19.
Biol Open ; 10(9)2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34494646

RESUMO

Well-orchestrated intercellular communication networks are pivotal to maintaining cardiac homeostasis and to ensuring adaptative responses and repair after injury. Intracardiac communication is sustained by cell-cell crosstalk, directly via gap junctions (GJ) and tunneling nanotubes (TNT), indirectly through the exchange of soluble factors and extracellular vesicles (EV), and by cell-extracellular matrix (ECM) interactions. GJ-mediated communication between cardiomyocytes and with other cardiac cell types enables electrical impulse propagation, required to sustain synchronized heart beating. In addition, TNT-mediated organelle transfer has been associated with cardioprotection, whilst communication via EV plays diverse pathophysiological roles, being implicated in angiogenesis, inflammation and fibrosis. Connecting various cell populations, the ECM plays important functions not only in maintaining the heart structure, but also acting as a signal transducer for intercellular crosstalk. Although with distinct etiologies and clinical manifestations, intercellular communication derailment has been implicated in several cardiac disorders, including myocardial infarction and hypertrophy, highlighting the importance of a comprehensive and integrated view of complex cell communication networks. In this review, I intend to provide a critical perspective about the main mechanisms contributing to regulate cellular crosstalk in the heart, which may be considered in the development of future therapeutic strategies, using cell-based therapies as a paradigmatic example. This Review has an associated Future Leader to Watch interview with the author.


Assuntos
Comunicação Celular/fisiologia , Estruturas da Membrana Celular/fisiologia , Junções Comunicantes/fisiologia , Cardiopatias/fisiopatologia , Miocárdio/citologia , Matriz Extracelular/fisiologia , Humanos , Miócitos Cardíacos/fisiologia , Nanotubos
20.
Pan Afr Med J ; 39: 173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34584599

RESUMO

The coronavirus disease-19 (COVID-19), first appearing in Wuhan, China, and later declared as a pandemic, has caused serious morbidity and mortality worldwide. Severe cases usually present with acute respiratory distress syndrome (ARDS), pneumonia, acute kidney injury (AKI), liver damage, or septic shock. However, with recent advances in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) research, the virus´s effect on cardiac tissues has become evident. Reportedly, an increased number of COVID-19 patients manifested serious cardiac complications such as heart failure, increased troponin, and N-terminal pro-B-type natriuretic peptide levels (NT-proBNP), cardiomyopathies, and myocarditis. These cardiac complications initially present as chest tightness, chest pain, and heart palpitations. Diagnostic investigations such as telemetry, electrocardiogram (ECG), cardiac biomarkers (troponin, NT-proBNP), and inflammatory markers (D-dimer, fibrinogen, PT, PTT), must be performed according to the patient´s condition. The best available options for treatment are the provision of supportive care, anti-viral therapy, hemodynamic monitoring, IL-6 blockers, statins, thrombolytic, and anti-hypertensive drugs. Cardiovascular disease (CVD) healthcare workers should be well-informed about the evolving research regarding COVID-19 and approach as a multi-disciplinary team to devise effective strategies for challenging situations to reduce cardiac complications.


Assuntos
COVID-19/complicações , Cardiopatias/virologia , SARS-CoV-2/isolamento & purificação , Biomarcadores/metabolismo , COVID-19/diagnóstico , Teste para COVID-19 , Cardiopatias/diagnóstico , Cardiopatias/fisiopatologia , Humanos , Equipe de Assistência ao Paciente/organização & administração
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