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1.
Int J Sports Med ; 41(1): 27-35, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791086

RESUMO

Several athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.


Assuntos
Futebol Americano/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Remodelação Ventricular/fisiologia , Adolescente , Afro-Americanos , Composição Corporal/fisiologia , Ecocardiografia , Grupo com Ancestrais do Continente Europeu , Ventrículos do Coração/anatomia & histologia , Humanos , Masculino , Fatores Raciais , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
2.
Expert Rev Cardiovasc Ther ; 17(11): 771-790, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31746657

RESUMO

Introduction: Obesity is associated with various diseases such as type 2 diabetes, hypertension, obstructive sleep apnea syndrome (OSAS), metabolic syndrome, and cardiovascular diseases. It affects several organ systems, including the pulmonary and cardiac systems. Furthermore, it induces pulmonary and cardiac changes that can result in right and/or left heart failure.Areas covered: In this review, authors provide an overview of obesity and cardiovascular remodeling, the individual actions of the gut hormones (like GLP-1 and PYY), the effects after bariatric/metabolic surgery and its influence on cardiac remodeling. In this review, we focussed and searched for literature in Pubmed and The Cochrane library (from the earliest date until April 2019), regarding cardiac function changes before and after bariatric surgery and literature regarding changes in gastrointestinal hormones.Expert opinion: Regarding the surgical treatment of obesity and metabolic diseases there is recognition of the importance of both weight loss (bariatric surgery) and improvement in metabolic milieu (metabolic surgery). A growing body of evidence further suggests that bariatric surgical procedures [like the Sleeve Gastrectomy (SG), Roux-en Y Gastric Bypass (RYGB), or One Anastomosis Gastric Bypass (OAGB)] have can improve outcomes of patients suffering from a number of cardiovascular diseases, including heart failure.


Assuntos
Hormônios Gastrointestinais/metabolismo , Obesidade/cirurgia , Remodelação Ventricular/fisiologia , Cirurgia Bariátrica/métodos , Gastrectomia , Derivação Gástrica , Humanos , Perda de Peso
3.
Basic Res Cardiol ; 114(5): 37, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31418072

RESUMO

In response to myocardial infarction (MI), neutrophils (PMNs) are early responders that initiate the inflammatory reaction. Because macrophages and fibroblasts show polarization states after MI, we hypothesized PMNs also undergo phenotypic changes over the MI time course. The objective of the current study was to map the continuum of polarization phenotypes in cardiac neutrophils over the first week of MI. C57BL/6J male mice (3-6 months old) underwent permanent coronary artery ligation to induce MI, and PMNs were isolated from the infarct region at days 1, 3, 5, and 7 after MI. Day 0 served as a no MI negative control. Aptamer proteomics was performed on biological replicates (n = 10-12) for each time point. Day (D)1 MI neutrophils had a high degranulation profile with increased matrix metalloproteinase (MMP) activity. D3 MI neutrophil profiles showed upregulation of apoptosis and induction of extracellular matrix (ECM) organization. D5 MI neutrophils further increased their ECM reorganization profile. D7 MI neutrophils had a reparative signature that included expression of fibronectin, galectin-3, and fibrinogen to contribute to scar formation by stimulating ECM reorganization. Of note, fibronectin was a key modulator of degranulation, as it amplified MMP-9 release in the presence of an inflammatory stimulus. Our results indicate that neutrophils selectively degranulate over the MI time course, reflective of both their intrinsic protein profiles as well as the ECM environment in which they reside. MMPs, cathepsins, and ECM proteins were prominent neutrophil degranulation indicators.


Assuntos
Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Neutrófilos , Animais , Degranulação Celular/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , Proteoma , Remodelação Ventricular/fisiologia
4.
Int J Mol Sci ; 20(16)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434314

RESUMO

Chagas disease (CD) affects approximately 6-7 million people worldwide, from which 30% develop chronic Chagas cardiomyopathy (CCC), usually after being asymptomatic for years. Currently available diagnostic methods are capable of adequately identifying infected patients, but do not provide information regarding the individual risk of developing the most severe form of the disease. The identification of biomarkers that predict the progression from asymptomatic or indeterminate form to CCC, may guide early implementation of pharmacological therapy. Here, six circulating microRNAs (miR-19a-3p, miR-21-5p, miR-29b-3p, miR-30a-5p, miR-199b-5p and miR-208a-3p) were evaluated and compared among patients with CCC (n = 28), CD indeterminate form (n = 10) and healthy controls (n = 10). MiR-19a-3p, miR-21-5p, and miR-29b-3p were differentially expressed in CCC patients when compared to indeterminate form, showing a positive correlation with cardiac dysfunction, functional class, and fibrosis, and a negative correlation with ejection fraction and left ventricular strain. Cardiac tissue analysis confirmed increased expression of microRNAs in CCC patients. In vitro studies using human cells indicated the involvement of these microRNAs in the processes of cardiac hypertrophy and fibrosis. Our study suggests that miRNAs are involved in the process of cardiac fibrosis and remodeling presented in CD and indicate a group of miRNAs as potential biomarkers of disease progression in CCC.


Assuntos
Biomarcadores/metabolismo , Cardiomiopatia Chagásica/metabolismo , Cardiomiopatia Chagásica/patologia , Fibrose/patologia , MicroRNAs/metabolismo , Biomarcadores/química , Cardiomiopatia Chagásica/genética , Feminino , Fibrose/genética , Fibrose/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Curva ROC , Remodelação Ventricular/genética , Remodelação Ventricular/fisiologia
5.
J Card Surg ; 34(10): 913-918, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31269266

RESUMO

OBJECTIVES: Degenerative mitral valve (MV) regurgitation (MR) is associated with left ventricular (LV) dilatation. Surgical treatment of MR has been shown to favorably affect LV remodeling. We prospectively compared the long-term echocardiographic outcomes of LV remodeling following mini-mitral repair for simple versus complex MV disease. METHODS: We prospectively followed up 203 consecutive patients who underwent mini-MV repair for severe degenerative MR over a 9-year period. Simple disease (n = 122 patients: posterior leaflet prolapse) was compared to complex disease (n = 81 patients: anterior, bilateral or commissural prolapse). Baseline demographics were similar between simple and complex groups (age: 63 ± 13 years vs 60 ± 15 years; p = .2; sex: 71% male vs 72% male, p = 1; preoperative MR grade ≥ 3+: 100%; n = 122; vs 100%; n = 81; p = 1), respectively. RESULTS: Preoperative left ventricular ejection fraction (LVEF) was significantly lower in the complex group as compared to the simple group (57.2% simple vs 56.0% complex; p = .04). Preoperative LV end-systolic diameter (LVESD: 35 mm simple vs 36 mm complex, p < .05) and LV end-diastolic diameter (LVEDD: 50 mm simple vs 51 mm complex; p < .05), as well as LV mass index (99.5 g/m2 vs 102.4 g/m2 ; p = .06) were larger in the complex group. Despite different baseline characteristics of LV function and geometry, both groups had similar remodeling of LV after MV repair. CONCLUSIONS: Patients with complex MV disease are referred late for surgical repair, causing LV function and dimensions to never fully recover. This suggests that earlier referral (before LV changes and potentially before symptoms) may be the preferred approach in those with complex disease.


Assuntos
Ventrículos do Coração/fisiopatologia , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Ecocardiografia , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/fisiopatologia , Período Pós-Operatório , Estudos Prospectivos , Índice de Gravidade de Doença , Volume Sistólico/fisiologia , Fatores de Tempo
6.
Clin Cardiol ; 42(10): 919-924, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301152

RESUMO

OBJECTIVES: The aim of the study was to confirm the value of the VALID-cardiac resynchronization therapy (CRT) risk score in predicting outcome and to assess its association with clinical response (CR) in an unselected real-world CRT population. METHODS AND RESULTS: The present analysis comprised all consecutive CRT patients (pts) enrolled in the CRT-MORE registry from 2011 to 2013. Pts were stratified into five groups (quintiles 1-5) according to the VALID-CRT risk predictor index applied to the CRT-MORE population. In the analysis of clinical outcome, adverse events comprised death from any cause and non-fatal heart failure (HF) events requiring hospitalization. CR at 12-month follow-up was also assessed. We enrolled 905 pts. During a median follow-up of 1005 [627-1361] days, 134 patients died, and 79 had at least one HF hospitalization. At 12 months, 69% of pts displayed an improvement in their CR. The mean VALID-CRT risk score derived from the CRT-MOdular Registry (MORE) population was 0.317, ranging from -0.419 in Q1 to 2.59 in Q5. The risk-stratification algorithm was able to predict total mortality after CRT (survival ranging from 93%-Q1 to 77%-Q5; hazards ratio [HR] = 1.42, 95% confidence interval [CI]: 1.25-1.61, P < .0001), and HF hospitalization (ranging from 95% to 90%; HR = 1.24, 95% CI: 1.06-1.45, P = .009). CR was significantly lower in pts with a high-to-very high risk profile (Q4-5) than in pts with a low-to-intermediate risk profile (Q1-2-3) (55% vs 79%, P < .0001). CONCLUSION: The VALID-CRT risk-stratification algorithm reliably predicts outcome and CRT response after CRT in an unselected, real-world population.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/terapia , Sistema de Registros , Medição de Risco/métodos , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Tempo
7.
Magn Reson Imaging Clin N Am ; 27(3): 427-437, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279447

RESUMO

Cardiac MR (CMR) imaging contributes uniquely to the comprehensive assessment and management of aortic stenosis (AS), beyond the information provided by transthoracic echocardiography. The severity of AS and subsequent ventricular remodeling response can be assessed using cine images and phase-contrast mapping. CMR imaging also identifies myocardial tissue characteristics, which are valuable markers of left ventricular decompensation and adverse outcomes in AS. CMR imaging may be used as an alternative modality for transcatheter aortic valve replacement (TAVR) planning and post-TAVR management. This article explores the clinical utility of CMR imaging evaluation.


Assuntos
Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Coração/diagnóstico por imagem , Coração/fisiopatologia , Imagem por Ressonância Magnética/métodos , Substituição da Valva Aórtica Transcateter , Velocidade do Fluxo Sanguíneo/fisiologia , Meios de Contraste , Gadolínio , Humanos , Aumento da Imagem/métodos , Imagem Cinética por Ressonância Magnética , Índice de Gravidade de Doença , Remodelação Ventricular/fisiologia
8.
Bull Exp Biol Med ; 167(3): 320-324, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31346866

RESUMO

Magnetic resonance imaging was employed to examine the morphofunctional status of myocardium in Wistar rats with multifactor cardiovasorenal model of arterial hypertension. In 3 months after the onset of experiment, the rats demonstrated a pronounced hypertrophy in left ventricular myocardium mostly due to thickening of the posterior and lateral walls against the background of relatively stable thickness of ventricular septum. The left ventricular endsystolic volume markedly increased in parallel with moderate increase of the end-diastolic volume. The standard calculated indices were used for precise assessment of the type of remodeling of individual myocardial structures. The study showed that multifactor arterial hypertension model was characterized by domination of hypertrophic mode of the left ventricular remodeling, whereas the concentric variant was observed more rarely by 2.5 times. The greatest alterations were observed in the posterior and lateral walls of the left ventricle, which could result from the hemodynamic effects of hypervolemic arterial hypertension.


Assuntos
Coração/fisiopatologia , Hipertensão/patologia , Miocárdio/patologia , Remodelação Ventricular/fisiologia , Animais , Imagem por Ressonância Magnética , Masculino , Ratos , Ratos Wistar , Função Ventricular Esquerda/fisiologia , Septo Interventricular/fisiologia
9.
Basic Res Cardiol ; 114(5): 33, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31312919

RESUMO

Leukocyte-mediated inflammation is central in atherothrombosis and ST-segment elevation myocardial infarction (STEMI). Neutrophil extracellular traps (NETs) have been shown to enhance atherothrombosis and stimulate fibroblast function. We analyzed the effects of NETs on cardiac remodeling after STEMI. We measured double-stranded (ds)DNA and citrullinated histone H3 (citH3) as NET surrogate markers in human culprit site and femoral blood collected during primary percutaneous coronary intervention (n = 50). Fibrocytes were characterized in whole blood by flow cytometry, and in culprit site thrombi and myocardium by immunofluorescence. To investigate mechanisms of fibrocyte activation, isolated NETs were used to induce fibrocyte responses in vitro. Enzymatic infarct size was assessed using creatine-phosphokinase isoform MB area under the curve. Left ventricular function was measured by transthoracic echocardiography. NET surrogate markers were increased at the culprit site compared to the femoral site and were positively correlated with infarct size and left ventricular dysfunction at follow-up. In vitro, NETs promoted fibrocyte differentiation from monocytes and induced fibrocyte activation. Highly activated fibrocytes accumulated at the culprit site and in the infarct transition zone. Our data suggest that NETs might be important mediators of fibrotic remodeling after STEMI, possibly by stimulating fibrocytes.


Assuntos
Armadilhas Extracelulares , Fibroblastos/patologia , Leucócitos/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Idoso , Feminino , Fibrose/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia
10.
Int Heart J ; 60(3): 715-727, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31105143

RESUMO

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.


Assuntos
Oclusão Coronária/patologia , Vasos Coronários/patologia , Microvasos/fisiopatologia , Remodelação Ventricular/fisiologia , Adulto , Animais , Angiografia Coronária/métodos , Angiografia Coronária/tendências , Oclusão Coronária/complicações , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Microcirculação/fisiologia , Microvasos/ultraestrutura , Modelos Animais , Infarto do Miocárdio/etiologia , Miocárdio/patologia , Suínos
11.
Minerva Cardioangiol ; 67(4): 261-271, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115242

RESUMO

BACKGROUND: Since left ventricular reverse remodeling (LVRR) and sphericity index (SI) are correlated with DCM patients' survival, we attempted to establish the relationship between LVRR, SI and left ventricle (LV) dimensions. METHODS: In 70 DCM patients, we measured EF, LV transverse (sLVd) and longitudinal (lLVd) diameters at hospital admission, then after 3 and 12 months. SI was assessed thus: SI=sLVd/lLVd. RESULTS: LVRR was present in 32 patients (52%). SI measurements were similar in LVRR-present and -absent groups at baseline (0.71 vs. 0.70) and differed after 3 and 12 months (0.61 vs. 0.72, P<0.005; 0.59 vs. 0.73, P<0.001; respectively). During 12 months, SI and sLVd decreased in the LVRR-present (0.71 vs. 0.61 vs. 0.59, P<0.05; 5.75 vs. 5.00 vs. 4.82 cm, P<0.001; respectively) and increased in the LVRR-absent cohort (0.70 vs. 0.72 vs. 0.73, P<0.001; 6.01 vs. 6.15 vs. 6.67, P<0.001; respectively). lLVd remained stable (8.23 vs. 8.16 vs. 8.38cm; 8.66 vs. 8.85 vs. 9.13 cm; respectively). SI was significantly correlated with sLVd but not with lLVd. At 3-month follow-up, SI (P<0.005, OR=14000 [95% CI: 5 - 3.9*107]) was found to be a significant LVRR predictor via univariate logistic regression. CONCLUSIONS: To summarize, changes in sLVd are crucial for changes in LV geometry, whereas lLVd has a negligible effect on this process. The presence of LVRR was not always associated with an improvement in SI and its absence with increase in SI. Since the assessment of SI is less complex than LVRR, SI as a significant LVRR predictor can be useful part of a regular echocardiography examination.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem
12.
Echocardiography ; 36(6): 1103-1109, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31116460

RESUMO

OBJECTIVE: The correlation between the echocardiographic Doppler flow parameters of microvascular obstruction (MVO) and coronary wedge pressure (CWP) measured as a marker of severe compressive microvascular dysfunction and a predictor of adverse left ventricular remodeling was evaluated in a group of high-risk acute anterior myocardial infarction survivors. METHODS: Twenty-four patients with mechanically reperfused anterior STEMI were divided into two groups based on the 38 mm Hg CWP cutoff for adverse left ventricular remodeling. Diastolic deceleration time (DDT), coronary flow reserve (CFR), systolic retrograde flow, peak systolic and peak diastolic velocities in the infarct-related artery were determined 3-5 days after revascularization. An echocardiographic 20% increase in left ventricular volumes defined adverse remodeling. RESULTS: No significant differences were recorded between groups with regard to the echocardiographic parameters of MVO. No significant correlation was identified between CWP on one side and DDT (P = 0.30) and CFR (P = 0.39) on the other, irrespective of total ischemic time and extracted thrombus length. No difference in 5 years of follow-up left ventricular remodeling was detected in patients with DDT<900 msec as compared to those with DDT≥900 msec. The medium increase in left ventricular end-systolic volume in patients with low CWP was 24.78%, while it reached 127.27% (P = 0.03) in patients with CWP>38 mm Hg. CONCLUSIONS: Coronary wedge pressure did not correlate with the surrogate parameters for MVO, but it was a predictor of left ventricular remodeling. None of the echocardiographic MVO parameters was associated with adverse remodeling at 5 years of follow-up.


Assuntos
Circulação Coronária/fisiologia , Trombose Coronária/diagnóstico por imagem , Ecocardiografia Doppler/métodos , Microcirculação/fisiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Remodelação Ventricular/fisiologia , Trombose Coronária/complicações , Trombose Coronária/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pressão Propulsora Pulmonar , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações
13.
Am J Physiol Regul Integr Comp Physiol ; 316(6): R776-R782, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042418

RESUMO

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.


Assuntos
Cardiomegalia/metabolismo , Miocárdio/metabolismo , Sistema Renina-Angiotensina/fisiologia , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Animais , Cardiomegalia/fisiopatologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos Endogâmicos BALB C , Miocárdio/patologia , Fragmentos de Peptídeos/metabolismo , Condicionamento Físico Animal , Receptor Tipo 1 de Angiotensina/metabolismo , Natação , Remodelação Ventricular/fisiologia
14.
Hypertension ; 74(1): 47-55, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132949

RESUMO

Emerging preclinical data suggest that splanchnic sympathetic nerve activation may play an important role in the pathophysiology of hypertension. We sought to determine the potential therapeutic application of catheter-based splanchnic denervation in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). Sustained elevated blood pressure was induced in adult pigs using a combination of intravenous infusion of Ang II (angiotensin II) and subcutaneous implantation of deoxycorticosterone acetate pellets to establish a large animal model of hCMP. Serial changes in cardiac echocardiographic and invasive hemodynamic parameters and neurohumoral biomarkers were investigated in animals with hypertension alone (n=9) and hypertension with catheter-based splanchnic denervation (n=6). Another 6 pigs without hypertension induction served as controls. At 10 weeks, hypertensive animals developed sustained elevated blood pressure and phenotype of hCMP with significant systolic and diastolic dysfunction, and left ventricular remodeling and hypertrophy as determined by invasive hemodynamic and echocardiogram assessments, respectively, and increased venoarterial norepinephrine gradient over the myocardium, kidneys, and splanchnic organs compared with baseline. Catheter-based splanchnic denervation decreased the venoarterial norepinephrine gradient over the splanchnic organs associated with the reduced splenic sympathetic nerve innervation; attenuated the elevated blood pressure, left ventricular remodeling, and hypertrophy; and preserved left ventricular systolic and diastolic function at 20 weeks in pigs with hCMP. Our results provide novel mechanistic insight into the role of splenic sympathetic nerve innervation in hypertension and important proof-of-principle data for the therapeutic application of catheter-based splanchnic denervation in a large animal model of hCMP.


Assuntos
Cateterismo Cardíaco/métodos , Cardiomiopatia Dilatada/cirurgia , Hipertensão/cirurgia , Nervos Esplâncnicos/cirurgia , Simpatectomia/métodos , Remodelação Ventricular/fisiologia , Análise de Variância , Animais , Determinação da Pressão Arterial , Cardiomiopatia Dilatada/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia/métodos , Feminino , Hemodinâmica , Hipertensão/fisiopatologia , Distribuição Aleatória , Valores de Referência , Medição de Risco , Sus scrofa , Resultado do Tratamento
15.
Cardiovasc Ultrasound ; 17(1): 6, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954080

RESUMO

BACKGROUND: The contractile response of patients with heart failure (HF) may be assessed by exercise stress echocardiography (ESE)-derived indexes. We sought to test whether ESE parameters are useful to identify the risk of adverse left ventricular (LV) remodeling in patients with chronic HF and reduced or mildly reduced LV ejection fraction (EF). METHODS: We enrolled 155 stabilized patients (age: 62 ± 11 years, 17% female, coronary artery disease 47%) with chronic HF, LV EF ≤50% and LV end-diastolic volume index > 75 ml/m2. All patients underwent a symptom-limited graded bicycle semi-supine ESE, with evaluation of peak stress LV EF, end-systolic pressure-volume relation (ESPVR, i.e. LV elastance) and cardiac power output to LV mass (CPOM). A complete echocardiographic study was performed at baseline and after 6 ± 3 months. Adverse LV remodeling was defined as the association of eccentric LV hypertrophy (LV mass: ≥115 g/m2 for male and ≥ 95 g/m2 for women, and relative wall thickness < 0.32) with an increase in LV end-systolic volume index ≥10% at six months. RESULTS: Adverse LV remodeling was detected in 34 (22%) patients. After adjustment for clinical, biochemical and echocardiographic data, peak ESPVR resulted in the most powerful independent predictor of adverse LV remodeling (OR: 12.5 [95% CI 4.5-33]; p < 0.0001) followed by ischemic aetiology (OR: 2.64 [95% 1.04-6.73]; p = 0.04). CONCLUSION: In patients with HF and reduced or mildly reduced EF, a compromised ESE-derived peak ESPVR, that reflects impaired LV contractility, resulted to be the most powerful predictor of adverse LV remodeling.


Assuntos
Ecocardiografia sob Estresse/métodos , Insuficiência Cardíaca/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/diagnóstico , Volume Sistólico/fisiologia , Pressão Ventricular/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Função Ventricular Esquerda/fisiologia
16.
Int J Exp Pathol ; 100(2): 102-113, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31017330

RESUMO

A major translational barrier to the use of stem cell (SC)-based therapy in patients with myocardial infarction (MI) is the lack of a clear understanding of the mechanism(s) underlying the cardioprotective effect of SCs. Numerous paracrine factors from SCs may account for reduction in infarct size, but myocardial salvage associated with transdifferentiation of SCs into vascular cells as well as cardiomyocyte-like cells may be involved too. In this study, bone marrow-derived rat mesenchymal SC (MSCs) were microencapsulated in alginate preventing viable cell release while supporting their secretory phenotype. The hypothesis on the key role of paracrine factors from MSCs in their cardioprotective activity was tested by comparison of the effect of encapsulated vs free MSCs in the rat model of MI. Intramyocardial administration of both free and encapsulated MSCs after MI caused reduction in scar size (12.1 ± 6.83 and 14.7 ± 4.26%, respectively, vs 21.7 ± 6.88% in controls, P = 0.015 and P = 0.03 respectively). Scar size was not different in animals treated with free and encapsulated MSC (P = 0.637). These data provide evidence that MSC-derived growth factors and cytokines are crucial for cardioprotection elicited by MSC. Administration of either free or encapsulated MSCs was not arrhythmogenic in non-infarcted rats. The consistency of our data with the results of other studies on the major role of MSC secretome components in cardiac protection further support the theory that the use of live, though encapsulated, cells for MI therapy may be replaced with heart-targeted-sustained delivery of growth factors/cytokines.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Alginatos , Animais , Arritmias Cardíacas/etiologia , Células Cultivadas , Cicatriz/patologia , Citoproteção/fisiologia , Composição de Medicamentos , Ecocardiografia , Imunofenotipagem , Masculino , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/imunologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Comunicação Parácrina/fisiologia , Ratos Wistar , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia
17.
Can J Cardiol ; 35(4): 490-500, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935640

RESUMO

BACKGROUND: The IκB kinase (IKK) complex has been found to have critical functions in cancer and the immune system. In particular, IKKα, which is a member of the IKK complex, has been shown to influence the inflammatory response and malignant diseases. However, the role of IKKα in macrophages after myocardial infarction (MI) remains largely unknown. METHODS: Sham or MI operations were performed on macrophage-specific IKKɑ knockout (mIKKɑ-/-) mice and IKKɑflox/flox littermates. We ligated the left anterior descending coronary artery of the MI group and observed the results at 3, 7, and 30 days after MI. RESULTS: We discovered more severe cardiac dysfunction with reduced angiogenesis, fibrosis, and collagen deposition in mIKKɑ-/- than in IKKɑflox/flox. In addition, we also observed that macrophages in mIKKɑ-/- were easier to polarize to the M1 phenotype and expressed more proinflammatory factors than IKKɑflox/flox. Mechanistically, IKKα deficiency in macrophages inhibited the alternative nuclear factor-κB/RelB pathway and enhanced the MEK1/2/ERK1/2 pathway. CONCLUSIONS: Overall, our data identified IKKɑ in the heart as a novel mediator that protected the heart from a severe inflammatory response and attenuated ventricular remodelling after MI by negatively regulating macrophage polarization to the M1 phenotype. Therefore, IKKα may serve as a potential therapeutic target for treatment after MI.


Assuntos
Quinase I-kappa B/metabolismo , Macrófagos/metabolismo , Infarto do Miocárdio/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Colágeno/metabolismo , Fibrose , Quinase I-kappa B/genética , MAP Quinase Quinase 1/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Macrófagos/imunologia , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Neovascularização Patológica/metabolismo
18.
J Cardiothorac Surg ; 14(1): 77, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30987651

RESUMO

PURPOSE: To evaluate the potential for right ventricular reverse remodelling after pulmonary valve replacement using cardiac magnetic resonance imaging, in adults with corrected tetralogy of Fallot and severe pulmonary insufficiency. MATERIAL AND METHODS: Ten patients with previous correction of tetralogy of Fallot with severe pulmonary insufficiency accepted for pulmonary valve replacement were evaluated prospectively with cardiac magnetic resonance imaging preoperatively and re-evaluated 10 ± 5 months postoperatively. Follow up for survival was 100% complete with mean of 37 ± 12 months. RESULTS: The preoperative mean indexed right ventricular end-diastolic volume was reduced from 161 ± 33 ml/m2 to 120 ± 23 ml/m2 postoperatively, p < 0.001. The preoperative mean indexed right ventricular stroke volume was reduced from 72 ± 20 ml/m2 to 50 ± 6 ml/m2 postoperatively, p = 0.002. After pulmonary valve replacement, the right ventricular ejection fraction did not change significantly (46% versus 42%, p = 0.337). Pulmonary insufficiency fraction decreased from 49% ± 11 to 1% ± 1 postoperatively, p < 0.001. CONCLUSIONS: Pulmonary valve replacement leads to a favourable early reverse remodelling with a reduction in RV volumes and improved function in all patients regardless of their preoperative indexed right ventricular volume.


Assuntos
Implante de Prótese de Valva Cardíaca , Imagem por Ressonância Magnética/métodos , Insuficiência da Valva Pulmonar/fisiopatologia , Tetralogia de Fallot/fisiopatologia , Função Ventricular Direita/fisiologia , Remodelação Ventricular/fisiologia , Adolescente , Adulto , Procedimentos Cirúrgicos Cardíacos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Prospectivos , Valva Pulmonar/diagnóstico por imagem , Valva Pulmonar/fisiopatologia , Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/cirurgia , Adulto Jovem
19.
Circ Res ; 124(9): 1323-1336, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30832557

RESUMO

RATIONALE: Targeting inflammation has been shown to provide clinical benefit in the field of cardiovascular diseases. Although manipulating regulatory T-cell function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. IL (interleukin)-35, an immunosuppressive cytokine mainly produced by regulatory T cells, is a novel member of the IL-12 family and is composed of an EBI3 (Epstein-Barr virus-induced gene 3) subunit and a p35 subunit. However, the role of IL-35 in infarct healing remains elusive. OBJECTIVE: This study aimed to determine whether IL-35 signaling is involved in healing and cardiac remodeling after myocardial infarction (MI) and, if so, to elucidate the underlying molecular mechanisms. METHODS AND RESULTS: IL-35 subunits (EBI3 and p35), which are mainly expressed in regulatory T cells, were upregulated in mice after MI. After IL-35 inhibition, mice showed impaired infarct healing and aggravated cardiac remodeling, as demonstrated by a significant increase in mortality because of cardiac rupture, decreased wall thickness, and worse cardiac function compared with wild-type MI mice. IL-35 inhibition also led to decreased expression of α-SMA (α-smooth muscle actin) and collagen I/III in the hearts of mice after MI. Pharmacological inhibition of IL-35 suppressed the accumulation of Ly6Clow and major histocompatibility complex IIlow/C-C motif chemokine receptor type 2- (MHC IIlow CCR2-) macrophages in infarcted hearts. IL-35 activated transcription of CX3CR1 (C-X3-C motif chemokine receptor 1) and TGF (transforming growth factor) ß1 in macrophages by inducing GP130 signaling, via IL12Rß2 and phosphorylation of STAT1 (signal transducer and activator of transcription family) and STAT4 and subsequently promoted Ly6Clow macrophage survival and extracellular matrix deposition. Moreover, compared with control MI mice, IL-35-treated MI mice showed increased expression of α-SMA and collagen within scars, correlating with decreased left ventricular rupture rates. CONCLUSIONS: IL-35 reduces cardiac rupture, improves wound healing, and attenuates cardiac remodeling after MI by promoting reparative CX3CR1+Ly6Clow macrophage survival.


Assuntos
Interleucinas/fisiologia , Macrófagos/fisiologia , Infarto do Miocárdio/fisiopatologia , Cicatrização/fisiologia , Transferência Adotiva , Animais , Anticorpos Monoclonais/farmacologia , Receptor 1 de Quimiocina CX3C/biossíntese , Receptor 1 de Quimiocina CX3C/genética , Sobrevivência Celular , Cicatriz/metabolismo , Proteínas da Matriz Extracelular/biossíntese , Regulação da Expressão Gênica/fisiologia , Ruptura Cardíaca Pós-Infarto/fisiopatologia , Ruptura Cardíaca Pós-Infarto/prevenção & controle , Interleucinas/antagonistas & inibidores , Interleucinas/biossíntese , Interleucinas/genética , Camundongos , Camundongos Endogâmicos C57BL , Antígenos de Histocompatibilidade Menor/biossíntese , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/imunologia , Miocárdio/metabolismo , Receptores de Citocinas/antagonistas & inibidores , Receptores de Citocinas/biossíntese , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/genética , Regulação para Cima , Remodelação Ventricular/fisiologia
20.
Am Heart J ; 211: 60-67, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30893577

RESUMO

BACKGROUND: Mineralocorticoid receptor antagonist (MRA) therapy has been shown to prevent adverse left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients with heart failure. Whether initiating MRA therapy prior to primary percutaneous coronary intervention (PPCI) accrues additional benefit of reducing myocardial infarct size and preventing adverse LV remodeling is not known. We aimed to investigate whether MRA therapy initiated prior to reperfusion reduces myocardial infarct (MI) size and prevents adverse LV remodeling in STEMI patients. METHODS: STEMI patients presenting within 12 hours and with a proximal coronary artery occlusion with Thrombolysis In Myocardial Infarction flow grade 0 were consented and randomized to either an intravenous bolus of potassium canrenoate, followed by oral spironolactone for 3 months or matching placebo. The primary endpoint was MI size by cardiovascular magnetic resonance at 3 months. RESULTS: Sixty-seven patients completed the study. There was no significant difference in the final MI size at 3 months between the 2 groups (placebo: 17 ± 11%, MRA: 16 ± 10%, P = .574). There was also no difference in acute MI size (26 ± 16% versus 23 ± 14%, P = .425) or myocardial salvage (26 ± 12% versus 24 ± 8%, P = .456). At follow-up, there was a trend towards an improvement in LVEF (placebo: 49 ± 8%, MRA: 54 ± 11%, P = .053), and the MRA group had significantly greater percentage decrease in LVEDV (mean difference: -12.2 (95% CI -20.3 to -4.4)%, P = .003) and LVESV (mean difference: -18.2 (95% CI -30.1 to -6.3)%, P = .003). CONCLUSION: This pilot study showed no benefit of MRA therapy in reducing MI size in STEMI patients when initiated prior to reperfusion, but there was an improvement in LV remodeling at 3 months. Adequately powered studies are warranted to confirm these findings.


Assuntos
Ácido Canrenoico/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Espironolactona/uso terapêutico , Idoso , Técnicas de Imagem Cardíaca , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudo de Prova de Conceito , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia
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