Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.635
Filtrar
1.
Int Heart J ; 62(4): 801-810, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276005

RESUMO

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to prevent left ventricular remodeling and improve outcomes of patients with heart failure (HF). This study aimed to investigate whether the use of ACEi/ARB could be associated with HF with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM).We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM between 2003 and 2014 from the clinical personal record, a national database of the Japanese Ministry of Health, Labour and Welfare. Patients with left ventricular ejection fraction (LVEF) < 40% were included. Eligible patients were divided into two groups according to the use of ACEi/ARB. A propensity score matching analysis was employed. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up.Out of 5,955 patients with DCM and LVEF < 40%, propensity score matching yielded 830 pairs. The mean age was 58.8 years, and 1,184 (71.3%) of the patients were male. The primary outcome was observed more frequently in the ACEi/ARB group than in the no ACEi/ARB group (57.0% versus 49.3%; odds ratio 1.36; 95% confidence interval (CI) 1.12-1.65; P = 0.002). Subgroup analysis revealed that the use of ACEi and ARB was associated with recovery of LVEF regardless of atrial fibrillation. The change in LVEF from baseline to 3 years of follow-up was greater in the ACEi-ARB group (14.9% ± 0.6% versus 12.3% ± 0.5%; P = 0.001).The use of ACEi/ARB is associated with HFrecEF in patients with DCM and reduced LVEF.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Cardiomiopatia Dilatada/tratamento farmacológico , Sistema de Registros , Volume Sistólico/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299304

RESUMO

Heart failure (HF) remains the leading cause of morbidity and death in the western world, and new therapeutic modalities are urgently needed to improve the lifespan and quality of life of HF patients. The sodium-glucose co-transporter-2 (SGLT2) inhibitors, originally developed and mainly indicated for diabetes mellitus treatment, have been increasingly shown to ameliorate heart disease, and specifically HF, in humans, regardless of diabetes co-existence. Indeed, dapagliflozin has been reported to reduce cardiovascular mortality and hospitalizations in patients with HF and reduced ejection fraction (HFrEF). This SGLT2 inhibitor demonstrates these benefits also in non-diabetic subjects, indicating that dapagliflozin's efficacy in HF is independent of blood glucose control. Evidence for the effectiveness of various SGLT2 inhibitors in providing cardiovascular benefits irrespective of their effects on blood glucose regulation have spurred the use of these agents in HFrEF treatment and resulted in FDA approvals for cardiovascular indications. The obvious question arising from all these studies is, of course, which molecular/pharmacological mechanisms underlie these cardiovascular benefits of the drugs in diabetics and non-diabetics alike. The fact that SGLT2 is not significantly expressed in cardiac myocytes (SGLT1 appears to be the dominant isoform) adds even greater perplexity to this answer. A variety of mechanisms have been proposed over the past few years and tested in cell and animal models and prominent among those is the potential for sympatholysis, i.e., reduction in sympathetic nervous system activity. The latter is known to be high in HF patients, contributing significantly to the morbidity and mortality of the disease. The present minireview first summarizes the current evidence in the literature supporting the notion that SGLT2 inhibitors, such as dapagliflozin and empagliflozin, exert sympatholysis, and also outlines the main putative underlying mechanisms for these sympatholytic effects. Then, we propose a novel hypothesis, centered on the adrenal medulla, for the sympatholytic effects specifically of dapagliflozin. Adrenal medulla is responsible for the production and secretion of almost the entire amount of circulating epinephrine and of a significant percentage of circulating norepinephrine in the human body. If proven true experimentally, this hypothesis, along with other emerging experimental evidence for sympatholytic effects in neurons, will shed new light on the pharmacological effects that mediate the cardiovascular benefits of SGLT2 inhibitor drugs, independently of their blood glucose-lowering effects.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Simpatolíticos/farmacologia , Glândulas Suprarrenais/fisiologia , Animais , Compostos Benzidrílicos/química , Fármacos Cardiovasculares/farmacologia , Catecolaminas/biossíntese , Glucosídeos/química , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Corpos Cetônicos/metabolismo , Modelos Biológicos , Receptores Acoplados a Proteínas G/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/química , Volume Sistólico/efeitos dos fármacos , Relação Estrutura-Atividade
3.
Biomed Pharmacother ; 138: 111531, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311530

RESUMO

Heart failure (HF) is the advanced heart disease with high morbidity and mortality. Compound DanShen Dripping Pill (CDDP) is a widely used Traditional Chinese Medicine for cardiovascular disease treatment. Herein, we investigated if CDDP can protect mice against doxorubicin (DOX) or isoprenaline (ISO)-induced HF. After 3 days feeding of normal chow containing CDDP, mice were started DOX or ISO treatment for 4 weeks or 18 days. At the end of treatment, mice were conducted electrocardiogram and echocardiographic test. Blood and heart samples were determined biochemical parameters, myocardial structure and expression of the related molecules. CDDP normalized DOX/ISO-induced heart weight changes, HF parameters and fibrogenesis. The DOX/ISO-impaired left ventricular ejection fraction and fractional shortening were restored by CDDP. Mechanistically, CDDP blocked DOX/ISO-inhibited expression of antioxidant enzymes and DOX/ISO-induced expression of pro-fibrotic molecules, inflammation and cell apoptosis. Additional DOX/ISO-impaired targets in cardiac function but protected by CDDP were identified by RNAseq, qRT-PCR and Western blot. In addition, CDDP protected cardiomyocytes against oxygen-glucose deprivation-induced injuries. Taken together, our study shows that CDDP can protect against myocardial injuries in different models, suggesting its potential application for HF treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Cardiopatias/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cardiotoxicidade , Linhagem Celular , Modelos Animais de Doenças , Doxorrubicina , Fibrose , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Mediadores da Inflamação/metabolismo , Isoproterenol , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
4.
Medicine (Baltimore) ; 100(25): e26396, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160422

RESUMO

BACKGROUND: Cardiovascular diseases have become a prominent threat to public health and quality of life. In recent years, some studies have reported that ivabradine can improve the cardiac function and prognosis of patients with acute myocardial infarction (AMI). Therefore, we perform a protocol for systematic review and meta-analysis to evaluate the efficacy of ivabradine for treating AMI. METHODS: This protocol of systematic review and meta-analysis has been drafted under the guidance of the preferred reporting items for systematic reviews and meta-analyses protocols. We will search PubMed, Cochrane Library, Embase, Web of Science, and Medline databases for relevant studies. In addition, we will also collect 4 databases of China: China National Knowledge Infrastructure, China Biomedical Literature Database, China Science Journal Database, and Wan-fang Database. Risk of bias will be assessed using the Cochrane Handbook risk of bias assessment tool version (V.5.1.0). We will use STATA 16.0 software (Stata Corporation, College Station, TX) to perform data analysis. RESULTS: The results of this systematic review and meta-analysis will be published in a peer-reviewed journal. CONCLUSION: We hypothesized that ivabradine can reduce the resting heart rate and improve heart function in patients with AMI.


Assuntos
Ivabradina/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Metanálise como Assunto , Infarto do Miocárdio/fisiopatologia , Descanso/fisiologia , Volume Sistólico/efeitos dos fármacos , Revisões Sistemáticas como Assunto , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
5.
Nurse Pract ; 46(7): 30-37, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34138811

RESUMO

ABSTRACT: Sodium-glucose cotransporter-2 (SGLT2) inhibitors can decrease risk for heart failure in patients with type 2 diabetes and can decrease risk of major cardiovascular events in patients with heart failure (HF) and diabetes. Specific SGLT2 inhibitors can also decrease major cardiovascular events in patients with HF only.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Ensaios Clínicos como Assunto , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/fisiopatologia , Humanos , Encaminhamento e Consulta , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Volume Sistólico/fisiologia , Resultado do Tratamento
8.
Muscle Nerve ; 64(2): 163-171, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34050938

RESUMO

INTRODUCTION/AIMS: The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin-converting enzyme-inhibitor (ACEi) and beta-blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated "cardiology-muscle" clinic. METHODS: This is an institutionally registered, retrospective, case-file-based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. RESULTS: Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1 ± 4.2 years, but older in those on maintenance steroid therapy (16.8 ± 4.2 vs 14.5 ± 4.1 years; P = .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. DISCUSSION: The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long-term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Cardiomiopatias/tratamento farmacológico , Distrofia Muscular de Duchenne/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Adolescente , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Cardiomiopatias/diagnóstico , Criança , Humanos , Masculino , Distrofia Muscular de Duchenne/diagnóstico , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Adulto Jovem
9.
J Toxicol Sci ; 46(5): 199-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952797

RESUMO

Cardiovascular complications have been well documented as the downside to conventional cancer chemotherapy. As a notable side effect of cisplatin (CDDP), cardiotoxicity represents a major obstacle to the successful treatment of cancer. It has been reported that Salvianolic acid B (SalB) possesses cardioprotective quality. However, the effect of SalB on cardiac damage caused by conventional cancer chemotherapy remains unclear. In this study, we clarified the protective effect of SalB on cisplatin-induced heart injury. Furthermore, in H9c2 cells, SalB dramatically reduced cisplatin-induced apoptosis and oxidative stress by modulating the nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway. In conclusion, SalB had great potential in mitigating cisplatin-induced cardiac injury. Furthermore, more attention should be placed on natural active compounds containing SalB with antioxidant effects for the treatment of cardiomyopathy.


Assuntos
Antineoplásicos , Antioxidantes/uso terapêutico , Benzofuranos/uso terapêutico , Cisplatino , Cardiopatias/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Antioxidantes/farmacologia , Benzofuranos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Creatina Quinase Forma MB/sangue , Coração/efeitos dos fármacos , Coração/fisiopatologia , Cardiopatias/induzido quimicamente , Cardiopatias/metabolismo , Cardiopatias/patologia , Heme Oxigenase-1/genética , L-Lactato Desidrogenase/sangue , Masculino , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , NAD(P)H Desidrogenase (Quinona)/genética , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos
10.
Am J Physiol Heart Circ Physiol ; 321(1): H175-H184, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34018850

RESUMO

Inorganic nitrite is a source of nitric oxide (NO) and is considered as a potential therapy in settings where endogenous NO bioactivity is reduced and left ventricular (LV) function impaired. However, the effects of nitrite on human cardiac contractile function, and the extent to which these are direct or indirect, are unclear. We studied 40 patients undergoing diagnostic cardiac catheterization who had normal LV systolic function and were not found to have obstructive coronary disease. They received either an intracoronary sodium nitrite infusion (8.7-26 µmol/min, n = 20) or an intravenous sodium nitrite infusion (50 µg/kg/min, n = 20). LV pressure-volume relations were recorded. The primary end point was LV end-diastolic pressure (LVEDP). Secondary end points included indices of LV systolic and diastolic function. Intracoronary nitrite infusion induced a significant reduction in LVEDP, LV end-diastolic pressure-volume relationship (EDPVR), and the time to LV end-systole (LVEST) but had no significant effect on LV systolic function or systemic hemodynamics. Intravenous nitrite infusion induced greater effects, with significant decreases in LVEDP, EDPVR, LVEST, LV dP/dtmin, tau, and mean arterial pressure. Inorganic nitrite has modest direct effects on human LV diastolic function, independent of LV loading conditions and without affecting LV systolic properties. However, the systemic administration of nitrite has larger effects on LV diastolic function, which are related to reduction in both preload and afterload. These contractile effects of inorganic nitrite may indicate a favorable profile for conditions characterized by LV diastolic dysfunction.NEW & NOTEWORTHY This is the first study to assess the direct and indirect effects of inorganic nitrite on invasive measures of left ventricular function in humans in vivo. Inorganic nitrite has a modest direct myocardial effect, improving diastolic function. Systemic administration of nitrite has larger effects related to alterations in cardiac preload and afterload. The changes induced by nitrite appear favorable for potential use in conditions characterized by LV diastolic dysfunction.


Assuntos
Contração Miocárdica/efeitos dos fármacos , Nitrito de Sódio/administração & dosagem , Sístole/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico/efeitos dos fármacos
11.
Medicine (Baltimore) ; 100(16): e25621, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879733

RESUMO

ABSTRACT: This study aimed to investigate the effects of the basic treatment for heart failure and sequential treatment with rh-brain natriuretic peptide (rhBNP) alone or the combination of rhBNP and sacubitril/valsartan. Cardiac structure, pulmonary artery pressure, inflammation and oxidative stress in patients with acute heart failure were evaluated.Three hundred patients with acute heart failure were included. According to the random number table method, the patients were divided into 3 groups of 100 patients per group: the standard treatment group (treated with an angiotensin-converting enzyme inhibitor, ß receptor blocker, and corticosteroid antagonist), rhBNP group (basic treatment combined with rhBNP) and sequential treatment group (basic treatment for heart failure combined with rhBNP followed by sacubitril/valsartan). The changes in NT-probrain natriuretic peptide (BNP) levels, cardiac troponin T (cTnT) levels, cardiac structure, pulmonary artery pressure, and the levels inflammatory factors and oxidative stress factors were compared among the 3 groups at 1, 4, 12, and 36 weeks after treatment.The sequential treatment group displayed superior outcomes than the standard treatment group and the rhBNP group in terms of left atrium diameter, left ventricular end diastolic volume, left ventricular ejection fraction, pulmonary artery pressure, NT-proBNP levels, and cTnT levels, which respond to damage to the heart structure and myocardium. This result may be related to the decreased levels of inflammatory factors and the correction of oxidative stress imbalance.Sacubitril/valsartan significantly reduce the serum levels of inflammatory factors in patients with acute heart failure while decreasing the levels of oxidizing factors and increasing the levels of antioxidant factors. These changes may be one of the explanations for the better cardiac structure and better pulmonary artery pressure observed in the sequential treatment group.


Assuntos
Aminobutiratos/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/administração & dosagem , Tetrazóis/administração & dosagem , Doença Aguda , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Pressão Arterial/efeitos dos fármacos , Biomarcadores/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Antagonistas de Hormônios/administração & dosagem , Humanos , Inflamação , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Volume Sistólico/efeitos dos fármacos , Resultado do Tratamento , Troponina T/sangue
12.
Curr Probl Cardiol ; 46(6): 100818, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33756178

RESUMO

In recent years, the cancer survival of patients has improved thanks to advances in the pharmacological field. In many guidelines, cardiotoxicity induced by anticancer drugs was defined as a reduction from baseline in the left ventricular ejection fraction (LVEF) assessed by echocardiography. It is known that LVEF is not a sensible parameter in the detection of cardiotoxicity. Therefore, a decrease from baseline in the global longitudinal strain (GLS) or troponins elevation is used to detect subclinical cardiotoxicity. LVEF and GLS as well as the increase in some biomarkers are influenced by loading conditions that are frequent during chemotherapy. Other parameters not influenced by loading conditions should be used in the early diagnosis of cardiotoxicity. The aim of this review is to delineate the role of current strategies used in the early diagnosis of cardiotoxicity and to identify new strategies that could have greater application in the future in cardioncology.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade , Ecocardiografia/métodos , Disfunção Ventricular Esquerda , Antineoplásicos/farmacologia , Biomarcadores/sangue , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Diagnóstico Precoce , Humanos , Imageamento por Ressonância Magnética , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Volume Sistólico/efeitos dos fármacos , Troponina/sangue , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos
13.
Circ Heart Fail ; 14(3): e007351, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33663236

RESUMO

BACKGROUND: New heart failure therapies that safely augment cardiac contractility and output are needed. Previous apelin peptide studies have highlighted the potential for APJ (apelin receptor) agonism to enhance cardiac function in heart failure. However, apelin's short half-life limits its therapeutic utility. Here, we describe the preclinical characterization of a novel, orally bioavailable APJ agonist, BMS-986224. METHODS: BMS-986224 pharmacology was compared with (Pyr1) apelin-13 using radio ligand binding and signaling pathway assays downstream of APJ (cAMP, phosphorylated ERK [extracellular signal-regulated kinase], bioluminescence resonance energy transfer-based G-protein assays, ß-arrestin recruitment, and receptor internalization). Acute effects on cardiac function were studied in anesthetized instrumented rats. Chronic effects of BMS-986224 were assessed echocardiographically in the RHR (renal hypertensive rat) model of cardiac hypertrophy and decreased cardiac output. RESULTS: BMS-986224 was a potent (Kd=0.3 nmol/L) and selective APJ agonist, exhibiting similar receptor binding and signaling profile to (Pyr1) apelin-13. G-protein signaling assays in human embryonic kidney 293 cells and human cardiomyocytes confirmed this and demonstrated a lack of signaling bias relative to (Pyr1) apelin-13. In anesthetized instrumented rats, short-term BMS-986224 infusion increased cardiac output (10%-15%) without affecting heart rate, which was similar to (Pyr1) apelin-13 but differentiated from dobutamine. Subcutaneous and oral BMS-986224 administration in the RHR model increased stroke volume and cardiac output to levels seen in healthy animals but without preventing cardiac hypertrophy and fibrosis, effects differentiated from enalapril. CONCLUSIONS: We identify a novel, potent, and orally bioavailable nonpeptidic APJ agonist that closely recapitulates the signaling properties of (Pyr1) apelin-13. We show that oral APJ agonist administration induces a sustained increase in cardiac output in the cardiac disease setting and exhibits a differentiated profile from the renin-angiotensin system inhibitor enalapril, supporting further clinical evaluation of BMS-986224 in heart failure.


Assuntos
Receptores de Apelina/agonistas , Débito Cardíaco/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Volume Sistólico/efeitos dos fármacos , Animais , Técnicas de Transferência de Energia por Ressonância de Bioluminescência , Células CHO , Cricetulus , Cães , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Haplorrinos , Humanos , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação , Ensaio Radioligante , Ratos , Trítio , Pressão Ventricular/efeitos dos fármacos , beta-Arrestinas/efeitos dos fármacos , beta-Arrestinas/metabolismo
14.
Biomed Pharmacother ; 138: 111316, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33684689

RESUMO

BACKGROUND: Cardiovascular diseases are the leading cause of death globally, and they are causing enormous socio-economic burden to the developed and developing countries. Allyl Methyl Sulfide (AMS) is a novel cardioprotective metabolite identified in the serum of rats after raw garlic administration. The present study explored the cardioprotective effect of AMS on thoracic aortic constriction (TAC)-induced cardiac hypertrophy and heart failure model in rats. METHODS: Thoracic aortic constriction (TAC) by titanium ligating clips resulted in the development of pressure overload-induced cardiac hypertrophy and heart failure model. Four weeks prior to TAC and for 8 weeks after TAC, Sprague Dawley (SD) rats were administered with AMS (25 and 50 mg/kg/day) or Enalapril (10 mg/kg/day). RESULTS: We have observed AMS (25 and 50 mg/kg/day) intervention significantly improved structural and functional parameters of the heart. mRNA expression of fetal genes i.e., atrial natriuretic peptide (ANP), alpha skeletal actin (α-SA) and beta myosin heavy chain (ß-MHC) were reduced in AMS treated TAC hearts along with decrease in perivascular and interstitial fibrosis. AMS attenuated lipid peroxidation and improved protein expression of endogenous antioxidant enzymes i.e., catalase and manganese superoxide dismutase (MnSOD) along with electron transport chain (ETC) complex activity. AMS increased mitochondrial fusion proteins i.e., mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy protein (OPA1), and reduced fission protein i.e., dynamin-related protein 1 (DRP1). Preliminary study suggests that AMS intervention upregulated genes involved in mitochondrial bioenergetics in normal rats. Further, in-vitro studies suggest that AMS reduced mitochondrial reactive oxygen species (ROS), preserved mitochondrial membrane potential and oxygen consumption rate (OCR) in isoproterenol-treated cardiomyoblast. CONCLUSION: This study demonstrated that AMS protected cardiac remodelling, LV dysfunction and fibrosis in pressure overload-induced cardiac hypertrophy and heart failure model by improving endogenous antioxidants and mitochondrial function.


Assuntos
Compostos Alílicos/uso terapêutico , Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Mitocôndrias Cardíacas/efeitos dos fármacos , Sulfetos/uso terapêutico , Compostos Alílicos/farmacologia , Animais , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/tratamento farmacológico , Cardiomegalia/fisiopatologia , Cardiotônicos/farmacologia , Linhagem Celular , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Masculino , Mitocôndrias Cardíacas/fisiologia , Ratos , Ratos Sprague-Dawley , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia , Sulfetos/farmacologia
15.
Oxid Med Cell Longev ; 2021: 8841575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33747351

RESUMO

The present study was performed to investigate whether H2S could restore the diurnal variation in cardiac function of aging mice and explore the potential mechanisms. We found that ejection fraction (EF) and fractional shortening (FS) in 3-month-old mice exhibited diurnal variations over a 24-hour period. However, the diurnal variations were disrupted in 18-month-old mice, and there was a decline in EF and FS. In addition, the plasma malondialdehyde (MDA) levels were increased, and H2S concentrations and superoxide dismutase (SOD) activities were decreased in 18-month-old mice. Then, CSE KO mice were used to determine if there was a relationship between endogenous H2S and diurnal variations in EF and FS. There was no difference in 12-hour averaged EF and FS between dark and light periods in CSE KO mice accompanying increased MDA levels and decreased SOD activities in plasma, indicating that deficiency of endogenous H2S blunted diurnal variations of cardiac function. To determine whether oxidative stress disrupted the diurnal variations in cardiac function, D-galactose-induced subacute aging mice were employed. After 3-month D-gal treatment, both 12-hour averaged EF and FS in dark or light periods were decreased; meanwhile, there was no difference in 12-hour averaged EF and FS between dark and light periods. After 3-month NaHS treatment in the D-gal group, the plasma MDA levels were decreased and SOD activities were increased. The EF and FS were lower during the 12-hour light period than those during the 12-hour dark period which was fit to sine curves in the D-gal+NaHS group. Identical findings were also observed in 18-month-old mice. In conclusion, our studies revealed that the disrupted diurnal variation in cardiac function was associated with increased oxidative stress and decreased H2S levels in aging mice. H2S could restore the diurnal variation in cardiac function of aging mice by reducing oxidative stress.


Assuntos
Envelhecimento/fisiologia , Ritmo Circadiano/efeitos dos fármacos , Coração/fisiopatologia , Sulfeto de Hidrogênio/farmacologia , Animais , Cistationina gama-Liase/metabolismo , Coração/efeitos dos fármacos , Testes de Função Cardíaca/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos
16.
Circ Heart Fail ; 14(3): e007048, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33663235

RESUMO

BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , COVID-19 , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Término Precoce de Ensaios Clínicos , Feminino , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Rim/fisiopatologia , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
17.
Circ Heart Fail ; 14(3): e007767, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33724883

RESUMO

BACKGROUND: The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS: One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS: The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS: CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


Assuntos
Canagliflozina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Telemedicina , Actigrafia/instrumentação , Canagliflozina/efeitos adversos , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Monitores de Aptidão Física , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Aplicativos Móveis , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Telemedicina/instrumentação , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Função Ventricular Esquerda/efeitos dos fármacos
18.
Ther Adv Cardiovasc Dis ; 15: 17539447211002678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33779401

RESUMO

Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic drug with salutary effects on glucose control, body weight, and blood pressure. Emerging evidence now indicates that these drugs may have a beneficial effect on outcomes in heart failure with reduced ejection fraction (HFrEF). Post-approval cardiovascular outcomes data for three of these agents (canagliflozin, empagliflozin, and dapagliflozin) showed an unexpected improvement in cardiovascular endpoints, including heart failure hospitalization and mortality, among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease or risk factors. These studies were followed by a placebo controlled trial of dapagliflozin in patients with HFrEF both with and without T2DM, showing a reduction in all-cause mortality comparable to current guideline-directed HFrEF medical therapies such as angiotensin-converting enzyme inhibitors and beta-blockers. In this review, we discuss the current landscape of evidence, safety and adverse effects, and proposed mechanisms of action for use of these agents for patients with HFrEF. The United States (US) and European guidelines are reviewed, as are the current US federally approved indications for each SGLT2 inhibitor. Use of these agents in clinical practice may be limited by an uncertain insurance environment, especially in patients without T2DM. Finally, we discuss practical considerations for the cardiovascular clinician, including within-class differences of the SGLT2 inhibitors currently available on the US market (217/300).


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Biomarcadores/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Progressão da Doença , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Recuperação de Função Fisiológica , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
20.
High Blood Press Cardiovasc Prev ; 28(2): 167-175, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33599965

RESUMO

INTRODUCTION: Sacubitril/valsartan (S-V) has been shown to reduce clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). This benefit has been mostly attributed to an improvement in systolic function. AIM: This study aimed to evaluate longitudinal changes in several echocardiographic parameters of diastolic function in a cohort of patients with HFrEF receiving S-V. METHODS: Echocardiographic parameters of consecutive patients receiving S-V, such as diastolic dysfunction (DD) grade and other individual diastolic and systolic function parameters, were prospectively collected at baseline and at 6-month follow-up. New York Heart Association (NYHA) functional class was also recorded. RESULTS: 65 patients (73.9% males; 61.5 ± 13 years) with HFrEF in NYHA class II-IV were evaluated. There was a significant reduction in DD grade after treatment with maximal tolerated doses (p < 0.001). Patients with advanced DD showed the most significant improvements: 75% and 60% of patients with initial grade 3 and 2, respectively, had better grade after 6 months of S-V. Moreover, there was a reduction in E/e' ratio (p = 0.004), left atrial longitudinal strain (p = 0.002), and an improvement of left ventricle ejection fraction (p < 0.001) and NYHA functional class (p = 0.001). Among those subjects who improved their functional class, a higher percentage improved their DD grade (39.3%, p = 0.025) in comparison with those not improving their NYHA class (25%, p = 0.434). CONCLUSIONS: In addition to an improvement in systolic function parameters, patients with HFrEF receiving S-V improved their diastolic function. This echocardiographic improvement is particularly relevant in those patients with better NYHA class at 6-month follow-up.


Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Idoso , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Diástole , Combinação de Medicamentos , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Recuperação de Função Fisiológica , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...