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1.
Am J Physiol Heart Circ Physiol ; 320(3): H980-H990, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416457

RESUMO

Perinatal hypoxia induces permanent structural and functional changes in the lung and its pulmonary circulation that are associated with the development of pulmonary hypertension (PH) in later life. The mechanistic target of the rapamycin (mTOR) pathway is vital for fetal lung development and is implicated in hypoxia-associated PH, yet its involvement in the developmental programming of PH remains unclear. Pregnant C57/BL6 dams were placed in hyperbaric (760 mmHg) or hypobaric chambers during gestation (505 mmHg, day 15 through postnatal day 4) or from weaning through adulthood (420 mmHg, postnatal day 21 through 8 wk). Pulmonary hemodynamics and right ventricular systolic pressure (RVSP) were measured at 8 wk. mTOR pathway proteins were assessed in fetal (day 18.5) and adult lung (8 wk). Perinatal hypoxia induced PH during adulthood, even in the absence of a sustained secondary hypoxic exposure, as indicated by reduced pulmonary artery acceleration time (PAAT) and peak flow velocity through the pulmonary valve, as well as greater RVSP, right ventricular (RV) wall thickness, and RV/left ventricular (LV) weight. Such effects were independent of increased blood viscosity. In fetal lung homogenates, hypoxia reduced the expression of critical downstream mTOR targets, most prominently total and phosphorylated translation repressor protein (4EBP1), as well as vascular endothelial growth factor, a central regulator of angiogenesis in the fetal lung. In contrast, adult offspring of hypoxic dams tended to have elevated p4EBP1 compared with controls. Our data suggest that inhibition of mTORC1 activity in the fetal lung as a result of gestational hypoxia may interrupt pulmonary vascular development and thereby contribute to the developmental programming of PH.NEW & NOTEWORTHY We describe the first study to evaluate a role for the mTOR pathway in the developmental programming of pulmonary hypertension. Our findings suggest that gestational hypoxia impairs mTORC1 activation in the fetal lung and may impede pulmonary vascular development, setting the stage for pulmonary vascular disease in later life.


Assuntos
Hipóxia Fetal/complicações , Hipertensão Pulmonar/etiologia , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Neovascularização Fisiológica , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Modelos Animais de Doenças , Feminino , Hipóxia Fetal/metabolismo , Hipóxia Fetal/fisiopatologia , Idade Gestacional , Hemodinâmica , Oxigenação Hiperbárica , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Camundongos Endogâmicos C57BL , Fosforilação , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Circulação Pulmonar , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Direita , Pressão Ventricular
2.
BMJ Case Rep ; 14(1)2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495174

RESUMO

Constrictive pericarditis is a relatively uncommon form of cardiac failure and presents due to scarring and consequent loss of the normal elasticity of the pericardial sac. This results in abnormal/limited ventricular filling and symptoms of heart failure. The aetiology is varied, from infective causes to idiopathic causes, or can manifest after cardiothoracic surgery. This case involves a 46-year-old man presenting with acute group A beta haemolytic streptococcus infection, and over the subsequent 6 months develops constrictive pericarditis due to what is believed to be a rheumatic aetiology. The patient subsequently underwent pericardiectomy and had restoration of normal filling dynamics confirmed on follow-up echocardiography. This case provides a subject matter for the review of the features of constrictive pericarditis and its investigation and management. This case is that it highlights the fact that pericarditis is not a benign condition. Emerging evidence suggests that pericarditis is due to a failure in inflammatory regulatory mechanisms, and patients suffering this condition have a preponderance to 'autoinflammation'. Pericarditis should be recognised early and treated fully with anti-inflammatory agents.


Assuntos
Bacteriemia/diagnóstico , Pericardite Constritiva/diagnóstico , Cardiopatia Reumática/diagnóstico , Infecções Estreptocócicas/diagnóstico , Antibacterianos/uso terapêutico , Antiestreptolisina/imunologia , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Hemocultura , Proteína C-Reativa/imunologia , Cateterismo Cardíaco , Ceftriaxona/uso terapêutico , Eletrocardiografia , Hospitalização , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pericardiectomia , Pericardite Constritiva/etiologia , Pericardite Constritiva/fisiopatologia , Pericardite Constritiva/cirurgia , Combinação Piperacilina e Tazobactam/uso terapêutico , Cardiopatia Reumática/etiologia , Cardiopatia Reumática/fisiopatologia , Cardiopatia Reumática/cirurgia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes , Pressão Ventricular
3.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431524

RESUMO

A 34-year-old woman was seen in the emergency department for shortness of breath and chest pain. During a pandemic, it is easy to 'think horses and not zebras', and with a patient presenting with the classic coronavirus symptoms it would have been easy to jump to that as her diagnosis. After a careful history and examination, it became clear that there was another underlying diagnosis. Chest X-ray, echocardiogram and CT scan revealed marked right ventricular dilatation and pulmonary hypertension, alongside a persistent left superior vena cava (PLSVC). Further investigation with cardiac MRI and coronary angiography at a tertiary centre demonstrated that she not only have a PLSVC but also a partial anomalous pulmonary venous drainage and sinus venosus atrial septal defect. This case highlights the importance of considering all differentials and approaching investigations in a logical manner.


Assuntos
/diagnóstico , Dor no Peito/fisiopatologia , Dispneia/fisiopatologia , Comunicação Interatrial/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Hipertrofia Ventricular Direita/diagnóstico por imagem , Síndrome de Cimitarra/diagnóstico por imagem , Adulto , Cateterismo Cardíaco , Dor no Peito/etiologia , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Diagnóstico Diferencial , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico por imagem , Dilatação Patológica/fisiopatologia , Dispneia/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Comunicação Interatrial/complicações , Comunicação Interatrial/fisiopatologia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/complicações , Hipertrofia Ventricular Direita/fisiopatologia , Imagem por Ressonância Magnética , /fisiopatologia , Síndrome de Cimitarra/complicações , Síndrome de Cimitarra/fisiopatologia , Tomografia Computadorizada por Raios X , Pressão Ventricular
4.
Am J Cardiol ; 143: 80-88, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33359198

RESUMO

The American Society of Echocardiography and/or the European Association of Cardiovascular Imaging recommend a conventional algorithm for estimating left ventricular (LV) filling pressure in heart failure. However, several patients are classed as "indeterminate" due to their LV filling pressures being impossible to calculate. We investigated whether our new echocardiographic algorithm can predict clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF). We enrolled 754 consecutive patients from the PURSUIT-HFpEF registry. We used the new algorithm to divide them into 2 groups; a normal LV filling pressure group (N group) and a high LV filling pressure group (H group). The H group consisted of 342 patients. Over a mean follow-up of 342 days, 185 patients reached the primary composite end point (157 readmissions for worsening heart failure and 43 cardiovascular deaths). In a multivariable Cox analysis, being in the H group was significantly associated with an increased rate of cardiac events compared with the N group (hazard ratio: 1.71; 95% confidence interval: 1.17 to 2.50, p = 0.006). There were 56 patients (7%) who were assigned to "indeterminate" with the conventional algorithm. Using the new algorithm, we reclassified 16 patients (29%) into the H group and 40 patients (71%) into the N group. The Kaplan-Meier curves showed the reclassified H group had a significantly higher incidence of cardiac events than those assigned to the N group (p < 0.01). In conclusion, the present study demonstrated LV filling pressure assessed by our algorithm can predict clinical outcomes in patients with HFpEF.


Assuntos
Algoritmos , Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Pressão Ventricular , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico por imagem , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Volume Sistólico , Disfunção Ventricular Esquerda/fisiopatologia
5.
Am J Physiol Heart Circ Physiol ; 320(3): H1037-H1054, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33356963

RESUMO

Mechanical dyssynchrony (MD) affects left ventricular (LV) mechanics and coronary perfusion. To understand the multifactorial effects of MD, we developed a computational model that bidirectionally couples the systemic circulation with the LV and coronary perfusion with flow regulation. In the model, coronary flow in the left anterior descending (LAD) and left circumflex (LCX) arteries affects the corresponding regional contractility based on a prescribed linear LV contractility-coronary flow relationship. The model is calibrated with experimental measurements of LV pressure and volume, as well as LAD and LCX flow rate waveforms acquired under regulated and fully dilated conditions from a swine under right atrial (RA) pacing. The calibrated model is applied to simulate MD. The model can simultaneously reproduce the reduction in mean LV pressure (39.3%), regulated flow (LAD: 7.9%; LCX: 1.9%), LAD passive flow (21.6%), and increase in LCX passive flow (15.9%). These changes are associated with right ventricular pacing compared with RA pacing measured in the same swine only when LV contractility is affected by flow alterations with a slope of 1.4 mmHg/mL2 in a contractility-flow relationship. In sensitivity analyses, the model predicts that coronary flow reserve (CFR) decreases and increases in the LAD and LCX with increasing delay in LV free wall contraction. These findings suggest that asynchronous activation associated with MD impacts 1) the loading conditions that further affect the coronary flow, which may explain some of the changes in CFR, and 2) the coronary flow that reduces global contractility, which contributes to the reduction in LV pressure.NEW & NOTEWORTHY A computational model that couples the systemic circulation of the left ventricular (LV) and coronary perfusion with flow regulation is developed to study the effects of mechanical dyssynchrony. The delayed contraction in the LV free wall with respect to the septum has a significant effect on LV function and coronary flow reserve.


Assuntos
Estimulação Cardíaca Artificial/efeitos adversos , Circulação Coronária , Modelos Cardiovasculares , Contração Miocárdica , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Função Ventricular Direita , Animais , Simulação por Computador , Modelos Animais de Doenças , Volume Sistólico , Sus scrofa , Fatores de Tempo , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular
6.
Am J Physiol Heart Circ Physiol ; 319(4): H882-H892, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32822212

RESUMO

Diastolic dysfunction (DD) is a major component of heart failure with preserved ejection fraction (HFpEF). Accordingly, a profound understanding of the underlying biomechanical mechanisms involved in DD is needed to elucidate all aspects of HFpEF. In this study, we have developed a computational model of DD by leveraging the power of an advanced one-dimensional arterial network coupled to a four-chambered zero-dimensional cardiac model. The two main pathologies investigated were linked to the active relaxation of the myocardium and the passive stiffness of the left ventricular wall. These pathologies were quantified through two parameters for the biphasic delay of active relaxation, which simulate the early and late-phase relaxation delay, and one parameter for passive stiffness, which simulates the increased nonlinear stiffness of the ventricular wall. A parameter sensitivity analysis was conducted on each of the three parameters to investigate their effect in isolation. The three parameters were then concurrently adjusted to produce the three main phenotypes of DD. It was found that the impaired relaxation phenotype can be replicated by mainly manipulating the active relaxation, the pseudo-normal phenotype was replicated by manipulating both the active relaxation and passive stiffness, and, finally, the restricted phenotype was replicated by mainly changing the passive stiffness. This article presents a simple model producing a holistic and comprehensive replication of the main DD phenotypes and presents novel biomechanical insights on how key parameters defining the relaxation and stiffness properties of the myocardium affect the development and manifestation of DD.NEW & NOTEWORTHY This study uses a complete and validated computational model of the cardiovascular system to simulate the two main pathologies involved in diastolic dysfunction (DD), i.e., abnormal active relaxation and increased ventricular diastolic stiffness. The three phenotypes of DD were successfully replicated according to literature data. We elucidate the biomechanical effect of the relaxation pathologies involved and how these pathologies interact to create the various phenotypes of DD.


Assuntos
Simulação por Computador , Insuficiência Cardíaca/fisiopatologia , Modelos Cardiovasculares , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Fenômenos Biomecânicos , Diástole , Humanos , Fenótipo , Volume Sistólico , Pressão Ventricular
7.
Heart Fail Clin ; 16(3): 255-269, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32503750

RESUMO

Acute myocardial infarction (AMI) results in significant changes in cardiac structure and functions, leading to left ventricular remodeling and subsequent systolic and diastolic dysfunction. To improve current approaches in diagnoses, treatments, and prevention of cardiovascular diseases, a better understanding of cardiac mechanoenergetics, including systolic performance and energy demand, becomes paramount. In this review, we summarize cardiac mechanics, cardiac energetics, and their relationship in complications related to AMI using 2 important physiologic frameworks, pressure-volume loops and the Vo2-pressure-volume area relationship diagram, as they are powerful tools for understanding physiologic behavior and mechanoenergetics of the left ventricle.


Assuntos
Insuficiência Cardíaca/etiologia , Ventrículos do Coração , Infarto do Miocárdio , Miocárdio/metabolismo , Tamanho do Órgão/fisiologia , Consumo de Oxigênio/fisiologia , Pressão Ventricular/fisiologia , Metabolismo Energético , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Modelos Cardiovasculares , Infarto do Miocárdio/complicações , Infarto do Miocárdio/metabolismo
8.
Int J Cardiovasc Imaging ; 36(9): 1659-1666, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32363448

RESUMO

Left ventricular diastolic dysfunction (LVDD) remains challenging to be assessed by echocardiography. We sought to explore the relationship between left atrial strain and left ventricular (LV) diastolic function in patients with normal left ventricular ejection fraction (LVEF) by invasive left-heart catheterization. 55 consecutive individuals with LVEF > 50% underwent LV catheterization. Standard transthoracic echocardiography was performed during 12 h before or after the procedure. Left atrial (LA) strain were obtained by speckle tracking echocardiography. When LVEF ≥ 50%, the group with elevated left ventricular end-diastolic pressure (LVEDP) (n = 35) showed decreased left atrial reservoir strain (LASr) (35.2 ± 7.7% vs 21.3 ± 7.2%, p < 0.001), left atrial conduit strain (LASct) (17.6 ± 6.3% vs 11.9 ± 4.1%, p < 0.001), left atrial contraction strain (LAScd) (16.6 ± 7.2% vs 9.5 ± 5.0%, p < 0.001) and increased E/e' ration(8.9 ± 2.6 vs 10.1 ± 3.5, p = 0.17). LVEDP negatively correlated with LASr (R = 0.662, p < 0.001), LASct (R = 0.575, p < 0.001) and LAScd (R = 0.456, p < 0.001), but not with E/e'. LASr, LASct and LAScd were all independent predictors of elevated LVEDP (p < 0.05), with a higher C-statistic for the model including LASr (0.95, 0.86 and 0.93 respectively). The area under the curve (AUC) for LASr is 0.914 (cutoff value is 26.7%, sensitivity is 90%, specificity is 82.9%). In patients with normal LV ejection fraction, left atrial strain presented good correlation with LVEDP, and LASr was superior to LASct and LAScd to predict LVEDP. LA strain demonstrated better agreement with the invasive reference than E/e'.


Assuntos
Função do Átrio Esquerdo , Cateterismo Cardíaco , Ecocardiografia Doppler , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Pressão Ventricular , Idoso , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Transdutores de Pressão , Disfunção Ventricular Esquerda/fisiopatologia
9.
Cardiovasc Drugs Ther ; 34(4): 487-501, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32377826

RESUMO

BACKGROUND: Previous studies have demonstrated that a high-carbohydrate intake could induce metabolic syndrome (MetS) in male rats with marked cardiac functional abnormalities. In addition, studies mentioned some benefits of insulin application on these complications, but there are considerable disagreements among their findings. Therefore, we aimed to extend our knowledge on the in-vitro influence of insulin on left ventricular dysfunction and also in the isolated cardiomyocytes from MetS rats. RESULTS: At the organ function level, an acute insulin application (100-nM) provided an important beneficial effect on the left ventricular developed pressure in MetS rats. Furthermore, to treat the freshly isolated cardiomyocytes from MetS rats with insulin provided marked recoveries in elevated resting intracellular Ca2+-level, as well as significant prevention of prolonged action potential through an augmentation in depressed K+-channel currents. Insulin also normalized the cellular levels of increased ROS and phosphorylation of PKCα, together with normalizations of apoptotic markers in MetS cardiomyocytes through the insulin-mediated regulation of phospho-Akt. Since not only elevated PKCα-activity but also reductions in phospho-Akt are key modulators of titin-based cardiomyocyte stiffening in hyperglycemia, insulin treatment of the cardiomyocytes prevented the activation of titin via the above pathways. Furthermore, CK2α-activation and NOS-phosphorylation could be prevented with insulin treatment. Mechanistically, we found that impaired insulin signaling and elevated PKCα and CK2α activities, as well as depressed Akt phosphorylation, are key modulators of titin-based cardiomyocyte stiffening in MetS rats. CONCLUSION: We propose that restoring normal kinase activities and also increases in phospho-Akt by insulin can contribute marked recoveries in MetS heart function, indicating a promising approach to modulate titin-associated factors in heart dysfunction associated with type-2 diabetes mellitus. Graphical Abstract.


Assuntos
Caseína Quinase II/metabolismo , Conectina/metabolismo , Hipoglicemiantes/farmacologia , Resistência à Insulina , Insulina/farmacologia , Síndrome Metabólica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Disfunção Ventricular Esquerda/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Modelos Animais de Doenças , Preparação de Coração Isolado , Masculino , Síndrome Metabólica/enzimologia , Síndrome Metabólica/fisiopatologia , Miócitos Cardíacos/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Disfunção Ventricular Esquerda/enzimologia , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular/efeitos dos fármacos
10.
Int J Cardiovasc Imaging ; 36(9): 1699-1709, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32440796

RESUMO

Measurement of pulmonary venous flow (PVF) parameters can be used to estimate left ventricular end-diastolic pressure (LVEDP) on transthoracic echocardiography. Despite that, 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging (EACVI) algorithm gave a secondary role to PVF to assess left ventricular filling pressure. We aimed to test correlations between several PVF parameters, including novel measurements, with LVEDP and to analyze whether PVF parameters have an incremental usefulness over ASE/EACVI algorithm to estimate LVEDP. Seventy-two patients that underwent left and right cardiac catheterization for assessment of heart failure or pulmonary hypertension were enrolled. All patients had a detailed echocardiographic study immediately before catheterization. Patients were categorized into those with an LVEDP < 15 mmHg vs. LVEDP ≥ 15 mmHg to analyze data. Patients with an elevated LVEDP had significantly lower peak S/D velocity ratio, S wave deceleration time, D wave acceleration time and D wave deceleration time (DWDT), as well as higher D wave acceleration rate (DWAR), but only peak S/D velocity ratio (ß = - 0.28, p = 0.01), DWDT (ß = - 0.33, p = 0.001) and DWAR (ß = 0.23, p = 0.03) were independent predictors for an elevated LVEDP. ASE/EACVI algorithm had a sensitivity of 71% and specificity of 74% to predict an elevated LVEDP. When PVF parameters were adjusted for ASE/EACVI algorithm; DWDT and DWAR remained as independent predictors. Sensitivity and specificity of ASE/EACVI algorithm increased to 79% and 96%, respectively, if either DWDT or DWAR was also suggestive of an elevated LVEDP. DWDT and DWAR have incremental usefulness over existing algorithm to determine LVEDP.


Assuntos
Ecocardiografia Doppler de Pulso , Insuficiência Cardíaca/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico por imagem , Circulação Pulmonar , Veias Pulmonares/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Pressão Ventricular , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Cateterismo Cardíaco , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Veias Pulmonares/fisiopatologia , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologia
11.
PLoS One ; 15(5): e0232544, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396557

RESUMO

This study examined the impact of septal flattening on left ventricular (LV) torsion in patients with precapillary pulmonary hypertension (PH). Fifty-two patients with proven precapillary PH and 13 healthy controls were included. Ventricular function was assessed including 4D-measurements, tissue velocity imaging, and speckle tracking analysis. Increased eccentricity index (1.39 vs. 1.08, p<0.001), systolic pulmonary artery pressure (64 vs. 29mmHg, p<0.001) and right ventricular Tei index (0.55 vs. 0.28, p = 0.007), and reduced tricuspid annular plane systolic excursion (19.0 vs. 26.5mm, p<0.001) were detected in PH patients as compared to controls. With increasing eccentricity of left ventricle, LV torsion was both decreased and delayed. Torsion rate paralleled this pattern of change during systole, but not during diastole. In conclusion, right ventricular pressure overload directly affects LV torsion mechanics. The echocardiographic methodology applied provides novel insights in the interrelation of right- and left ventricular function.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Direita/fisiologia , Pressão Ventricular/fisiologia , Adulto , Idoso , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Ecocardiografia , Humanos , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Estudos Retrospectivos , Torção Mecânica , Disfunção Ventricular Esquerda/etiologia
12.
Sci Rep ; 10(1): 7180, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32346030

RESUMO

Assessment of intraventricular pressure gradients (IVPG) using color Doppler M-mode echocardiography has gained increasing interest in the evaluation of cardiac function. However, standardized analysis tools for IVPG quantification are missing. We aimed to evaluate the feasibility, the test-retest observer reproducibility, and the inter-system variability of a semi-automated IVPG quantification algorithm. The study included forty healthy volunteers (50% were men). All volunteers were examined using two ultrasound systems, the Philips Epiq 7 and the General Electric Vivid 6. Left ventricular diastolic (DIVPG) and systolic (SIVPG) intraventricular pressure gradients were measured from the spatiotemporal distribution of intraventricular propagation flow velocities using color Doppler M-mode in standard apical views. There was good feasibility for both systolic and diastolic IVPG measurements (82.5% and 85%, respectively). Intra and inter-observer test-retest variability measured with the intraclass correlation coefficient were 0.98 and 0.93 for DIVPG respectively, and 0.95 and 0.89 for SIVPG respectively. The inter-system concordance was weak to moderate with Lin's concordance correlation coefficient of 0.59 for DIVPG and 0.25 for SIVPG. In conclusion, it is feasible and reproducible to assess systolic and diastolic IVPG using color Doppler M-mode in healthy volunteers. However, the inter-system variability in IVPG analysis needs to be taken into account, especially when using displayed data.


Assuntos
Pressão Sanguínea , Diástole , Ecocardiografia Doppler em Cores , Ventrículos do Coração , Sístole , Pressão Ventricular , Adolescente , Adulto , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Masculino
14.
Methodist Debakey Cardiovasc J ; 16(1): 43-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280417

RESUMO

Cardiogenic shock (CS) is a complex syndrome of end-organ hypoperfusion that requires timely and thorough decision making. While many pathophysiologic and technical principles have been delineated in this issue, the purpose of this case-based report is to reflect upon some of these principles in the context of real-life scenarios. Given the obvious lacuna of evidence-based recommendations in CS, the authors provide a rationale for their decision-making process. The first case is a young post-heart-transplant patient with graft failure who was in a state of biventricular failure and restrictive physiology and required acute mechanical circulatory support (MCS). The second case is a patient who suffered a mechanical complication after experiencing an acute myocardial infarction that required MCS.


Assuntos
Rejeição de Enxerto/etiologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração/efeitos adversos , Modelos Cardiovasculares , Infarto do Miocárdio/complicações , Choque Cardiogênico/fisiopatologia , Função Ventricular Esquerda , Função Ventricular Direita , Pressão Ventricular , Idoso , Cardiotônicos/uso terapêutico , Oxigenação por Membrana Extracorpórea , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Coração Auxiliar , Humanos , Balão Intra-Aórtico/instrumentação , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Volume Sistólico , Resultado do Tratamento , Adulto Jovem
16.
J Cardiovasc Magn Reson ; 22(1): 21, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32241289

RESUMO

BACKGROUND: Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. METHODS: We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. RESULTS: We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections (p < 0.001, R2 = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. CONCLUSIONS: These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a non-invasive, comprehensive method to detect regional structural myocyte LV remodeling during disease.


Assuntos
Tamanho Celular , Imagem de Tensor de Difusão , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Miócitos Cardíacos/patologia , Função Ventricular Esquerda , Pressão Ventricular , Remodelação Ventricular , Animais , Modelos Animais de Doenças , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Valor Preditivo dos Testes , Ratos Sprague-Dawley
17.
PLoS One ; 15(3): e0229609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126071

RESUMO

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Modelos Cardiovasculares , Pressão Ventricular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Feminino , Humanos , Masculino , Método de Monte Carlo , Contração Miocárdica/fisiologia , Modelagem Computacional Específica para o Paciente , Estudos Prospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
18.
Braz J Med Biol Res ; 53(3): e8761, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159612

RESUMO

Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.


Assuntos
Cálcio/análise , Inibidores Enzimáticos/farmacologia , Contração Miocárdica/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/efeitos dos fármacos , Condicionamento Físico Animal/fisiologia , Adiposidade , Animais , Peso Corporal/fisiologia , Inibidores Enzimáticos/administração & dosagem , Hemodinâmica , Masculino , Modelos Animais , Atividade Motora/fisiologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , NG-Nitroarginina Metil Éster/administração & dosagem , Óxido Nítrico Sintase/metabolismo , Ratos Wistar , Pressão Ventricular/efeitos dos fármacos
20.
J Cardiovasc Pharmacol ; 75(5): 460-474, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32195757

RESUMO

Estrogenic deficiency is considered a risk of coronary disease in women. The phytoestrogen genistein could be a safe preventive strategy. The first aim of this work was to validate a model of cardiac stunning in which natural estrogenic deficiency rats, ie, adult young male (YM) and aged female (AgF), are compared with young female rats (YF). The second aim was to study whether the in vivo administration of genistein prevents the stunning in estrogenic deficiency rats. The third aim was to evaluate whether in our estrogenic deficiency model exists a synergy between genistein and estradiol. The fourth aim was to characterize the underlying mechanisms of genistein. Stunning was induced by ischemia/reperfusion (I/R) in isolated hearts inside a calorimeter. The left ventricular pressure (P) and total heat rate (Ht) were simultaneously measured, while diastolic contracture and muscle economy (P/Ht) were calculated. During R, P/Ht and P recovered less in AgF and YM than in YF rat hearts. Genistein through i.p. (GST-ip) improved P and P/Ht in AgF and YM, but not in YF. In YM, the cardioprotections of GST-ip and estradiol were synergistic. After ischemia, GST-ip increased SR Ca leak causing diastolic contracture. The GST-ip cardioprotection neither was affected by blockade of PI3K-Akt, NO synthases, or phosphatases, but it was sensitive to blockade of protein-kinase C and mKATP channels. Results suggest that (1) estrogenic deficiency worsens cardiac stunning, (2) GST-ip was more cardioprotective in estrogenic deficiency and synergistic with estradiol, and (3) cardioprotection of GST-ip depends on the protein-kinase C and mKATP channel pathway activation.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Genisteína/farmacologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio Atordoado/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fitoestrógenos/farmacologia , Canais de Potássio/metabolismo , Fatores Etários , Animais , Sinalização do Cálcio , Modelos Animais de Doenças , Estradiol/farmacologia , Feminino , Preparação de Coração Isolado , Masculino , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio Atordoado/enzimologia , Miocárdio Atordoado/patologia , Miocárdio Atordoado/fisiopatologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Proteína Quinase C/metabolismo , Ratos Sprague-Dawley , Fatores Sexuais , Função Ventricular Esquerda/efeitos dos fármacos , Pressão Ventricular/efeitos dos fármacos
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