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1.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360595

RESUMO

After myocardial infarction (MI), a strong inflammatory response takes place in the heart to remove the dead tissue resulting from ischemic injury. A growing body of evidence suggests that timely resolution of this inflammatory process may aid in the prevention of adverse cardiac remodeling and heart failure post-MI. The present challenge is to find a way to stimulate this process without interfering with the reparative role of the immune system. Extracellular vesicles (EVs) are natural membrane particles that are released by cells and carry different macromolecules, including proteins and non-coding RNAs. In recent years, EVs derived from various stem and progenitor cells have been demonstrated to possess regenerative properties. They can provide cardioprotection via several mechanisms of action, including immunomodulation. In this review, we summarize the role of the innate immune system in post-MI healing. We then discuss the mechanisms by which EVs modulate cardiac inflammation in preclinical models of myocardial injury through regulation of monocyte influx and macrophage function. Finally, we provide suggestions for further optimization of EV-based therapy to improve its potential for the treatment of MI.


Assuntos
Cardiotônicos/administração & dosagem , Vesículas Extracelulares/transplante , Inflamação/terapia , Infarto do Miocárdio/complicações , Células-Tronco/citologia , Animais , Humanos , Inflamação/etiologia , Inflamação/patologia
2.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203800

RESUMO

Accumulating evidence support the cardioprotective properties of the nuclear receptor peroxisome proliferator activated receptor ß/δ (PPARß/δ); however, the underlying mechanisms are not yet fully elucidated. The aim of the study was to further investigate the mechanisms underlying PPARß/δ-mediated cardioprotection in the setting of myocardial ischemia/reperfusion (I/R). For this purpose, rats were treated with PPARß/δ agonist GW0742 and/or antagonist GSK0660 in vivo and hearts were subjected to ex vivo global ischemia followed by reperfusion. PPARß/δ activation improved left ventricular developed pressure recovery, reduced infarct size (IS) and incidence of reperfusion-induced ventricular arrhythmias while it also up-regulated superoxide dismutase 2, catalase and uncoupling protein 3 resulting in attenuation of oxidative stress as evidenced by the reduction in 4-hydroxy-2-nonenal protein adducts and protein carbonyl formation. PPARß/δ activation also increased both mRNA expression and enzymatic activity of aldehyde dehydrogenase 2 (ALDH2); inhibition of ALDH2 abrogated the IS limiting effect of PPARß/δ activation. Furthermore, upregulation of PGC-1α and isocitrate dehydrogenase 2 mRNA expression, increased citrate synthase activity as well as mitochondrial ATP content indicated improvement in mitochondrial content and energy production. These data provide new mechanistic insight into the cardioprotective properties of PPARß/δ in I/R pointing to ALDH2 as a direct downstream target and suggesting that PPARß/δ activation alleviates myocardial I/R injury through coordinated stimulation of the antioxidant defense of the heart and preservation of mitochondrial function.


Assuntos
Aldeído-Desidrogenase Mitocondrial/metabolismo , Cardiotônicos/uso terapêutico , Metabolismo Energético , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo , PPAR delta/metabolismo , PPAR beta/metabolismo , Proteína 4 Semelhante a Angiopoietina/metabolismo , Animais , Antioxidantes/metabolismo , Caderinas/metabolismo , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacologia , Catalase/metabolismo , Metabolismo Energético/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Modelos Biológicos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , PPAR delta/agonistas , PPAR beta/agonistas , Ratos Wistar , Superóxido Dismutase/metabolismo , Tiazóis/administração & dosagem , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Proteína Desacopladora 3/metabolismo , Regulação para Cima/efeitos dos fármacos
3.
Phytomedicine ; 88: 153597, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34111614

RESUMO

BACKGROUND: Doxorubicin (DOX) is a widely used antitumor drug. However, its clinical application is limited for its serious cardiotoxicity. The mechanism of DOX-induced cardiotoxicity is attributed to the increasing of cell stress in cardiomyocytes, then following autophagic and apoptotic responses. Our previous studies have demonstrated the protective effect of Shenmai injection (SMI) on DOX-induced cardiotoxicity via regulation of inflammatory mediators for releasing cell stress. PURPOSE: To further investigate whether SMI attenuates the DOX-induced cell stress in cardiomyocytes, we explored the mechanism underlying cell stress as related to Jun N-terminal kinase (JNK) activity and the regulation of autophagic flux to determine the mechanism by which SMI antagonizes DOX-induced cardiotoxicity. STUDY DESIGN: The DOX-induced cardiotoxicity model of autophagic cell death was established in vitro to disclose the protected effects of SMI on oxidative stress, autophagic flux and JNK signaling pathway. Then the autophagic mechanism of SMI antagonizing DOX cardiotoxicity was validated in vivo. RESULTS: SMI was able to reduce the DOX-induced cardiomyocyte apoptosis associated with inhibition of activation of the JNK pathway and the accumulation of reactive oxygen species (ROS). Besides, SMI antagonized DOX cardiotoxicity, regulated cardiomyocytes homeostasis by restoring DOX-induced cardiomyocytes autophagy. Under specific circumstances, SMI depressed autophagic process by reducing the Beclin 1-Bcl-2 complex dissociation which was activated by DOX via stimulating the JNK signaling pathway. At the same time, SMI regulated lysosomal pH to restore the autophagic flux which was blocked by DOX in cardiomyocytes. CONCLUSION: SMI regulates cardiomyocytes apoptosis and autophagy by controlling JNK signaling pathway, blocking DOX-induced apoptotic pathway and autophagy formation. SMI was also found to play a key role in restoring autophagic flux for counteracting DOX-damaged cardiomyocyte homeostasis.


Assuntos
Cardiotônicos/farmacologia , Cardiotoxicidade/tratamento farmacológico , Doxorrubicina/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Cardiotônicos/administração & dosagem , Cardiotoxicidade/metabolismo , Linhagem Celular , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Injeções , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
4.
Am Heart J ; 239: 11-18, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33984317

RESUMO

OBJECTIVE: The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT). BACKGROUND: With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care. METHODS: We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded. RESULTS: Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT. CONCLUSIONS: AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.


Assuntos
Assistência Ambulatorial , Cardiotônicos , Insuficiência Cardíaca , Taquicardia Ventricular , Assistência Ambulatorial/métodos , Assistência Ambulatorial/estatística & dados numéricos , Circulação Assistida/instrumentação , Circulação Assistida/métodos , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Cardiotônicos/classificação , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/métodos , Hospitalização/estatística & dados numéricos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Gravidade do Paciente , Alta do Paciente , Medição de Risco , Índice de Gravidade de Doença , Volume Sistólico , Análise de Sobrevida , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/prevenção & controle , Estados Unidos/epidemiologia
5.
Food Funct ; 12(8): 3657-3671, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33900312

RESUMO

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3 polyunsaturated fatty acids, flavanols and phytosterols has many beneficial effects on cardiovascular disease. However, their combined actions on the risk factors for atherosclerosis remains poorly understood. We have previously shown that a formulation containing each of these active components at physiologically relevant doses modulated several monocyte/macrophage processes associated with atherosclerosis in vitro, including inhibition of cytokine-induced pro-inflammatory gene expression, chemokine-driven monocyte migration, expression of M1 phenotype markers, and promotion of cholesterol efflux. The objectives of the present study were to investigate whether the protective actions of the formulation extended in vivo and to delineate the potential underlying mechanisms. The formulation produced several favourable changes, including higher plasma levels of HDL and reduced levels of macrophages and myeloid-derived suppressor cells in the bone marrow. The mRNA expression of liver-X-receptor-α, peroxisome proliferator-activated receptor-γ and superoxide dismutase-1 was induced in the liver and that of interferon-γ and the chemokine (C-X-C motif) ligand 1 decreased, thereby suggesting the potential mechanisms for many beneficial effects. Other changes were also observed such as increased plasma levels of triglycerides and lipid peroxidation that may reflect potential activation of brown fat. This study provides new insights into the protective actions and the potential underlying mechanisms of the formulation in vivo, particularly in relation to risk factors together with changes in systemic inflammation and hepatic lipid alterations associated with atherosclerosis and metabolic syndrome, and supports further assessments in human trials.


Assuntos
Cardiotônicos/farmacologia , Doença da Artéria Coronariana/prevenção & controle , Animais , Cardiotônicos/administração & dosagem , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/administração & dosagem , Flavanonas/administração & dosagem , Alimento Funcional , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fitosteróis/administração & dosagem , Fatores de Risco
6.
Int J Mol Sci ; 22(9)2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33925062

RESUMO

Cardiovascular disease is a leading cause of death globally, presenting an immense public and economic burden. Studies on cardioprotective foods and their bioactive components are needed to address both personal and public health needs. Date fruit is rich in polyphenols, particularly flavonoids, certain micronutrients, and dietary fiber, which can impact vascular health, and have the potential to attenuate vascular disease in humans. Data from in vitro and animal studies report that consumption of date fruit or extracts can modulate select markers of vascular health, particularly plasma lipid levels including triglycerides and cholesterol, indices of oxidative stress and inflammation, but human data is scant. More investigation is needed to better characterize date polyphenols and unique bioactive compounds or fractions, establish safe and effective levels of intake, and delineate underlying mechanisms of action. Implementing scientific rigor in clinical trials and assessment of functional markers of vascular disease, such as flow-mediated dilation and peripheral arterial tonometry, along with gut microbiome profiles would provide useful information with respect to human health. Emerging data supports the notion that intake of date fruit and extracts can be a useful component of a healthy lifestyle for those seeking beneficial effects on vascular health.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Frutas , Phoeniceae , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/química , Doenças Cardiovasculares/sangue , Feminino , Frutas/química , Humanos , Lipídeos/sangue , Masculino , Phoeniceae/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem
7.
Medicine (Baltimore) ; 100(15): e25551, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847683

RESUMO

BACKGROUND: The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed. RESULTS: Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ±â€Š33.7 vs 93.4 ±â€Š30.9, P = .016; 114.3 ±â€Š34.3 vs 94.7 ±â€Š33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ±â€Š10.5 vs 13.5 ±â€Š5.0, P = .003; 20.2 ±â€Š7.4 vs 15.2 ±â€Š5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ±â€Š30.9 vs 112.1 ±â€Š31.9, P = .739), cTFC (19.4 ±â€Š7.2 vs 19.3 ±â€Š7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate. CONCLUSIONS: The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.


Assuntos
Alprostadil/administração & dosagem , Cardiotônicos/administração & dosagem , Infarto do Miocárdio/terapia , Nicorandil/administração & dosagem , Nitroglicerina/administração & dosagem , Vasodilatadores/administração & dosagem , Idoso , Vias de Administração de Medicamentos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Coração/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Perfusão , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
9.
Food Funct ; 12(7): 3069-3082, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33720242

RESUMO

The reduction in estrogen levels is associated with the increased risk factors for cardiovascular disease development. The present study aimed to evaluate the effect of chia consumption in a standard diet (SD) or high fat diet (HFD) on ovariectomized (OVX) and non-ovariectomized (SHAM) rats, in relation to biometric measurements, oxidative stress, mineral content and ATPase enzymes in the heart. The study was conducted with 80 female Wistar rats, which received a SD or HFD for 18 weeks. During the first 7 weeks, the animals received the SD or HFD. Then, 40 rats were ovariectomized and 40 rats were SHAM operated. After recovery from surgery, the animals were allocated to 8 groups (n = 10) and they received one of the following diets for 8 weeks: SD, SD + chia, HFD and HFD + chia. In the OVX group, HFD increased weight gain, adiposity, cardiac hypertrophy, and nitric oxide (NO) and K concentration and decreased the Na+/K+ATPase activity. In combination with HFD, ovariectomy decreased the catalase activity, Mg, Cu and Zn concentration, total ATPase activity, and Na+/K+ATPase and Mg2 + ATPase activities; this group also presented higher NO, Ca, K, Fe and Mn concentration in the heart. The SHAM group fed chia presented a lower fat content in the heart. In the OVX group fed HFD, chia increased the activity of superoxide dismutase, decreased NO and maintained the content of minerals and ATPase enzymes. Thus, chia improved the biometric parameters of the heart, the antioxidant activity and maintained the content of minerals and ATPase enzymes, showing a cardioprotective action, but without reversing the deleterious effects of ovariectomy.


Assuntos
Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Extratos Vegetais/uso terapêutico , Salvia , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Obesidade , Ovariectomia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
11.
Expert Rev Anti Infect Ther ; 19(9): 1083-1092, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33618607

RESUMO

Introduction: The novel coronavirus has caused significant mortality worldwide and is primarily associated with severe acute respiratory distress syndrome (ARDS). Apart from ARDS, clinical reports have shown noticeable cardiovascular complications among the patients of COVID-19. Infection from virus, stimulation of cytokine storm, altered immune response, and damage to myocardial tissue are some of the proposed mechanisms of cardiovascular complications in COVID-19.Areas covered: Based on the clinical reports of CVDs among COVID-19 patients, we have discussed the molecular mechanisms involved in cardiovascular pathogenesis, its prevalence, and association with COVID-19, and various available therapeutic modality for the treatment.Expert opinion: Seeing the cardiovascular complications in COVID-19 patients and its association with the existing drug, risk-benefit ratio of treatment paradigm, as well as the level of cardiac injury biomarkers must be monitored regularly. Additionally, a well-designed clinical trial should be conducted where head to head comparison can be made with anti-COVID-19 drugs and cardioprotective anti-inflammatory drugs. Nevertheless, vaccines are the best-suited approach, but until then, sanitization, social distancing, and active lifestyle are the best ways to beat this global pandemic situation.


Assuntos
COVID-19/complicações , Doenças Cardiovasculares/prevenção & controle , Anti-Inflamatórios/administração & dosagem , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Cardiotônicos/administração & dosagem , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/virologia , Humanos
12.
J Tradit Chin Med ; 41(1): 140-149, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33522207

RESUMO

OBJECTIVE: To investigate the relationship between the cardiotonic activity of Fuzi (Radix Aconiti Lateralis Preparata, RALP) and its fingerprint determined by liquid chromatography-mass spectrometry (LC-MS). METHODS: First, the fingerprints of six processed products of RALP were established by high performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS) followed by analysis of the principal component of the relative peak area of its common peaks. Next, the scores of the first five principal components were used as input for an artificial neural network (ANN). Additionally, the therapeutic effect of RALP was assessed by measuring the hemodynamic indexes of heart failure model rats. Subsequently, fluorescence semi-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay kit were used to determine the effects of RALP-processed products on the serum levels of noradrenaline (NA), angiotensin-Ⅰ (Ang-Ⅰ), and the expression of ß-norepinephrine receptor mRNA (ß-NRm) in the rat cardiac tissues. P < 0.05 was used as the output of the ANN. Finally, a network was constructed to display the relationship between the LC-MS fingerprints and the cardiotonic activity of the RALP-processed products. RESULTS: Several types of RALPs can improve diastolic function, systolic function and heart rate. On the basis of the findings from the principal component analysis (PCA) of 16 common peaks of fingerprints of six RALP-processed products, it was revealed that the first five principal components may include 100% of the information of the original data. As observed from the multilayer perceptron neural network analysis, principal component 4 presented with the strongest effects on serum levels of NA and Ang-Ⅰ in rats, while principal component 1 exerted the greatest effect on ß-NRm expression in cardiac tissue. CONCLUSION: The key findings obtained from this study indicated that the network constructed by the PCA-ANN may predict pharmacodynamic effects of the main ingredients of Traditional Chinese Medicine (TCM). This method may serve as a new approach to identify the relationship between LC-MS fingerprints and the pharmacodynamic effects of TCM ingredients.


Assuntos
Aconitum/química , Cardiotônicos/química , Medicamentos de Ervas Chinesas/química , Insuficiência Cardíaca/tratamento farmacológico , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Cardiotônicos/administração & dosagem , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Humanos , Masculino , Espectrometria de Massas , Norepinefrina/genética , Norepinefrina/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos/genética , Receptores Adrenérgicos/metabolismo
13.
Arch Dis Child Fetal Neonatal Ed ; 106(4): 398-403, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33627329

RESUMO

OBJECTIVE: To determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation. DESIGN: Double-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment. SETTING: 10 sites across Europe and Canada. PARTICIPANTS: Infants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage. INTERVENTION: Participants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management). PRIMARY OUTCOME: Survival to 36 weeks of PMA without severe brain injury. RESULTS: The trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038). CONCLUSION: Though this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area. TRIAL REGISTRATION NUMBER: NCT01482559, EudraCT 2010-023988-17.


Assuntos
Cardiotônicos/uso terapêutico , Dopamina/uso terapêutico , Hipotensão/tratamento farmacológico , Lactente Extremamente Prematuro , Lesões Encefálicas/induzido quimicamente , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Dopamina/administração & dosagem , Dopamina/efeitos adversos , Método Duplo-Cego , Idade Gestacional , Humanos , Hipotensão/mortalidade , Recém-Nascido
15.
Chem Phys Lipids ; 235: 105057, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33515592

RESUMO

A close link between cardiovascular diseases and cancer results from sharing the same modifiable risk factors (e.g. nutritional) and cardiotoxicity of anti-cancerous therapies. It justifies cardio-oncological preliminary studies on dietary factors, especially on those of possible anti-carcinogenic or cardioprotective properties. The main purpose was to evaluate the effect of pomegranate seed oil (PSO) and/or bitter melon extract (BME) supplementation of the diet of female rats suffering from mammary tumors on lipidomic profile (expressed as fatty acids, conjugated fatty acids (CFA), malondialdehyde (MDA), cholesterol and oxysterols content) of cardiac tissue. Total lipidomic profile and intensity of lipid peroxidation in hearts of DMBA-treated Sprague-Dawley rats and their healthy equivalents, both obtaining diet supplementation, were evaluated with different chromatographic techniques coupled with appropriate detection systems (GC-MS, GC-TOFMS, Ag+-HPLC-DAD, UF-HPLC-DAD). Dietary modifications neither diminished breast cancer incidence nor exerted explicit cardio-protective influence, however, they diminished cholesterol content, i.a. because of inhibition of the endogenous conversion of squalene to cholesterol in cardiac tissue. CFA were incorporated into cardiac tissue to a lesser extent in the cancerous process. PSO and BME anti-oxidant properties in pathological condition were only slightly reflected in MDA levels but not in oxysterols formation. Obtained results indicate considerable changes in dietary supplements' biological activity in pathological conditions and the need for clear distinction of drugs and dietary supplements, which is of utmost importance, especially for cancer survivors.


Assuntos
Anticarcinógenos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cardiotônicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Oxisteróis/metabolismo , Extratos Vegetais/farmacologia , Óleos Vegetais/farmacologia , Animais , Anticarcinógenos/administração & dosagem , Anticarcinógenos/química , Neoplasias da Mama/metabolismo , Cardiotônicos/administração & dosagem , Cardiotônicos/química , Doenças Cardiovasculares/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Lipidômica , Momordica charantia/química , Miocárdio/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Óleos Vegetais/administração & dosagem , Óleos Vegetais/química , Romã (Fruta)/química , Ratos , Ratos Sprague-Dawley
16.
Sci Rep ; 11(1): 683, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436841

RESUMO

Ballistocardiography (BCG) and Seismocardiography (SCG) assess the vibrations produced by cardiac contraction and blood flow, respectively, by means of micro-accelerometers and micro-gyroscopes. From the BCG and SCG signals, maximal velocities (VMax), integral of kinetic energy (iK), and maximal power (PMax) can be computed as scalar parameters, both in linear and rotational dimensions. Standard echocardiography and 2-dimensional speckle tracking imaging echocardiography were performed on 34 healthy volunteers who were infused with increasing doses of dobutamine (5-10-20 µg/kg/min). Linear VMax of BCG predicts the rates of left ventricular (LV) twisting and untwisting (both p < 0.0001). The linear PMax of both SCG and BCG and the linear iK of BCG are the best predictors of the LV ejection fraction (LVEF) (p < 0.0001). This result is further confirmed by mathematical models combining the metrics from SCG and BCG signals with heart rate, in which both linear PMax and iK strongly correlate with LVEF (R = 0.7, p < 0.0001). In this setting of enhanced inotropism, the linear VMax of BCG, rather than the VMax of SCG, is the metric which best explains the LV twist mechanics, in particular the rates of twisting and untwisting. PMax and iK metrics are strongly associated with the LVEF and account for 50% of the variance of the LVEF.


Assuntos
Balistocardiografia/métodos , Dobutamina/administração & dosagem , Ecocardiografia/métodos , Ventrículos do Coração/fisiopatologia , Contração Miocárdica , Função Ventricular Esquerda/fisiologia , Adolescente , Adulto , Cardiotônicos/administração & dosagem , Feminino , Voluntários Saudáveis , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Adulto Jovem
17.
Mar Drugs ; 19(2)2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33498729

RESUMO

Several cardioprotective mechanisms attributed to Omega-3 polyunsaturated fatty acids (PUFAs) have been studied and widely documented. However, in recent years, studies have supported the concept that the intestinal microbiota can play a much larger role than we had anticipated. Microbiota could contribute to several pathologies, including cardiovascular diseases. Indeed, an imbalance in the microbiota has often been reported in patients with cardiovascular disease and produces low-level inflammation. This inflammation contributes to, more or less, long-term development of cardiovascular diseases. It can also worsen the symptoms and the consequences of these pathologies. According to some studies, omega-3 PUFAs in the diet could restore this imbalance and mitigate its harmful effects on cardiovascular diseases. Many mechanisms are involved and included: (1) a reduction of bacteria producing trimethylamine (TMA); (2) an increase in bacteria producing butyrate, which has anti-inflammatory properties; and (3) a decrease in the production of pro-inflammatory cytokines. Additionally, omega-3 PUFAs would help maintain better integrity in the intestinal barrier, thereby preventing the translocation of intestinal contents into circulation. This review will summarize the effects of omega-3 PUFAs on gut micro-biota and the potential impact on cardiac health.


Assuntos
Cardiotônicos/administração & dosagem , Doenças Cardiovasculares/dietoterapia , Ácidos Graxos Ômega-3/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Cardiotônicos/metabolismo , Doenças Cardiovasculares/metabolismo , Dieta Saudável/métodos , Dieta Saudável/tendências , Disbiose/dietoterapia , Disbiose/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Humanos
19.
J Pharmacol Exp Ther ; 376(1): 127-135, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33100271

RESUMO

The practice of prescribing ß-blockers to lower blood pressure and mitigate perioperative cardiovascular events has been questioned because of reports of an increased risk of stroke. The benefit of ß-blocker therapy primarily relies on preventing activation of cardiac ß1-adrenergic receptors (ARs). However, we reported that ß1ARs also mediate vasodilator responses of rat cerebral arteries (CAs), implying that ß-blockers may impair cerebral blood flow under some conditions. Here, we defined the impact of metoprolol (MET), a widely prescribed ß1AR-selective antagonist, on adrenergic-elicited diameter responses of rat CAs ex vivo and in vivo. MET (1-10 µmol/l) prevented ß1AR-mediated increases in diameter elicited by dobutamine in cannulated rat CAs. The ß1AR-mediated dilation elicited by the endogenous adrenergic agonist norepinephrine (NE) was reversed to a sustained constriction by MET. Acute oral administration of MET (30 mg/kg) to rats in doses that attenuated resting heart rate and dobutamine-induced tachycardia also blunted ß1AR-mediated dilation of CAs. In the same animals, NE-induced dilation of CAs was reversed to sustained constriction. Administration of MET for 2 weeks in drinking water (2 mg/ml) or subcutaneously (15 mg/kg per day) also resulted in NE-induced constriction of CAs in vivo. Thus, doses of MET that protect the heart from adrenergic stimulation also prevent ß1AR-mediated dilation of CAs and favor anomalous adrenergic constriction. Our findings raise the possibility that the increased risk of ischemic stroke in patients on ß-blockers relates in part to adrenergic dysregulation of cerebrovascular tone. SIGNIFICANCE STATEMENT: ß-Blocker therapy using second-generation, cardioselective ß-blockers is associated with an increased risk of stroke, but the responsible mechanisms are unclear. Here, we report that either acute or chronic systemic administration of a cardioselective ß-blocker, metoprolol, mitigates adrenergic stimulation of the heart as an intended beneficial action. However, metoprolol concomitantly eliminates vasodilator responses to adrenergic stimuli of rat cerebral arteries in vivo as a potential cause of dysregulated cerebral blood flow predisposing to ischemic stroke.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Cardiotônicos/farmacologia , Artérias Cerebrais/efeitos dos fármacos , Metoprolol/farmacologia , Receptores Adrenérgicos beta 1/metabolismo , Vasodilatação , Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/efeitos adversos , Artérias Cerebrais/fisiologia , Dobutamina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Metoprolol/administração & dosagem , Metoprolol/efeitos adversos , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley
20.
Curr Pharm Biotechnol ; 22(3): 367-379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-31696816

RESUMO

BACKGROUND: Oleaster or Elaeagnus angustifolia is a deciduous plant from Elaegnacea family and is well-known for its remedial applications. OBJECTIVE: This paper presents a comprehensive review of the potential application of Oleaster's flour incorporated in some food products. Emphasis is given to the physicochemical, biochemical, and functional properties of Oleaster's flour. METHODS: A comprehensive search was carried out to find publications on Oleaster's flour and its application as a prebiotic. The results of the related studies were extracted and summarized in this paper. RESULTS: Oleaster's flour as a prebiotic ingredient enhances antioxidants, polyphenols, fiber, flavonoids, Sterols, carbohydrates, and protein content of food products. CONCLUSION: Further advanced investigations on Oleaster and its functional ingredients revealed that these are efficacious and can be applied as a substitute source in pharmacological industries for medical applications.


Assuntos
Elaeagnaceae , Etnobotânica/métodos , Farinha/análise , Extratos Vegetais/análise , Prebióticos/análise , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/análise , Anti-Inflamatórios/química , Antioxidantes/administração & dosagem , Antioxidantes/análise , Antioxidantes/química , Cardiotônicos/administração & dosagem , Cardiotônicos/análise , Cardiotônicos/química , Elaeagnaceae/química , Flavonoides/administração & dosagem , Flavonoides/análise , Flavonoides/química , Humanos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Polifenóis/administração & dosagem , Polifenóis/análise , Polifenóis/química , Prebióticos/administração & dosagem
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