ANTONIO AUGUSTO BARBOSA LOPES

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Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina

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Autor: MAEDA, Nair Y. ×

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  • article 0 Citação(ões) na Scopus
    Respiratory viruses and postoperative hemodynamics in patients with unrestrictive congenital cardiac communications: a prospective cohort study
    (2023) ABUD, Kelly C. O.; MACHADO, Clarisse M.; BOAS, Lucy S. Vilas S.; MAEDA, Nair Y.; CARVALHO, Eloisa S.; SOUZA, Maria Francilene S.; GAIOLLA, Paula V.; CASTRO, Claudia R. P.; PEREIRA, Juliana; RABINOVITCH, Marlene; LOPES, Antonio Augusto
    BackgroundPulmonary vascular abnormalities pose a risk for severe life-threatening hemodynamic disturbances following surgical repair of congenital cardiac communications (CCCs). In the distal lung, small airways and vessels share a common microenvironment, where biological crosstalks take place. Because respiratory cells infected by viruses express a number of molecules with potential impact on airway and vascular remodeling, we decided to test the hypothesis that CCC patients carrying viral genomes in the airways might be at a higher risk for pulmonary (and systemic) hemodynamic disturbances postoperatively.MethodsSixty patients were prospectively enrolled (age 11 [7-16] months, median with interquartile range). Preoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP) was 0.78 (0.63-0.88). The presence or absence of genetic material for respiratory viruses in nasopharyngeal and tracheal aspirates was investigated preoperatively in the absence of respiratory symptoms using real-time polymerase chain reaction (kit for detection of 19 pathogens). Post-cardiopulmonary bypass (CPB) inflammatory reaction was analyzed by measuring serum levels of 36 inflammatory proteins (immunoblotting) 4 h after its termination. Postoperative hemodynamics was assessed using continuous recording of PAP and SAP with calculation of PAP/SAP ratio.ResultsViral genomes were detected in nasopharynx and the trachea in 64% and 38% of patients, respectively. Rhinovirus was the most prevalent agent. The presence of viral genomes in the trachea was associated with an upward shift of postoperative PAP curve (p = 0.011) with a PAP/SAP of 0.44 (0.36-0.50) in patients who were positive versus 0.34 (0.30-0.45) in those who were negative (p = 0.008). The presence or absence of viral genomes in nasopharynx did not help predict postoperative hemodynamics. Postoperative PAP/SAP was positively correlated with post-CPB levels of interleukin-1 receptor antagonist (p = 0.026), macrophage migration inhibitory factor (p = 0.019) and monocyte chemoattractant protein-1 (p = 0.031), particularly in patients with virus-positive tracheal aspirates.ConclusionsPatients with CCCs carrying respiratory viral genomes in lower airways are at a higher risk for postoperative pulmonary hypertension, thus deserving special attention and care. Preoperative exposure to respiratory viruses and post-CPB inflammatory reaction seem to play a combined role in determining the postoperative behavior of the pulmonary circulation.
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    Circulating Levels of MIF, GRO alpha And RANTES Chemokines and Interleukin 17E Correlate With Severity of Pulmonary Hypertension in Young Pediatric Patients With Congenital Heart Disease
    (2015) ZORZANELLI, Leina; MAEDA, Nair Y.; CLEVE, Mariana M.; THOMAZ, Ana M.; RABINOVITCH, Marlene; LOPES, Antonio A.
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    Increased Expression of Platelet Membrane Glycoprotein IIb/IIIa (GPIIb/IIIa) is Associated With Pulmonary Vasoreactivity After Pediatric Cardiac Surgery.
    (2018) MAEDA, Nair Y.; CLAVE, Mariana M.; CARVALHO, Eloisa S.; GALAS, Filomena R.; BYDLOWSKI, Sergio P.; LOPES, Antonio A.
  • article 3 Citação(ões) na Scopus
    Postoperative Pulmonary Hemodynamics and Systemic Inflammatory Response in Pediatric Patients Undergoing Surgery for Congenital Heart Defects
    (2022) SOUZA, Maria Francilene S.; PENHA, Juliano G.; MAEDA, Nair Y.; GALAS, Filomena R. B. G.; ABUD, Kelly C. O.; CARVALHO, Eloisa S.; THOMAZ, Ana Maria; CASTRO, Claudia R. P.; PEREIRA, Juliana; LOPES, Antonio Augusto
    There is scarce information about the relationships between postoperative pulmonary hemodynamics, inflammation, and outcomes in pediatric patients with congenital cardiac communications undergoing surgery. We prospectively studied 40 patients aged 11 (8-17) months (median with interquartile range) with a preoperative mean pulmonary arterial pressure of 48 (34-54) mmHg who were considered to be at risk for postoperative pulmonary hypertension. The immediate postoperative pulmonary/systemic mean arterial pressure ratio (PAP/SAP(IPO), mean of first 4 values obtained in the intensive care unit, readings at 2-hour intervals) was correlated directly with PAP/SAP registered in the surgical room just after cardiopulmonary bypass (r=0.68, p < 0.001). For the entire cohort, circulating levels of 15 inflammatory markers changed after surgery. Compared with patients with PAP/SAP(IPO)& LE;0.40 (n=22), those above this level (n=18) had increased pre- and postoperative serum levels of granulocyte colony-stimulating factor (p=0.040), interleukin-1 receptor antagonist (p=0.020), interleukin-6 (p=0.003), and interleukin-21 (p=0.047) (panel for 36 human cytokines) and increased mean platelet volume (p=0.018). Using logistic regression analysis, a PAP/SAP(IPO)> 0.40 and a heightened immediate postoperative serum level of macrophage migration inhibitory factor (quartile analysis) were shown to be predictive of significant postoperative cardiopulmonary events (respective hazard ratios with 95% CIs, 5.07 (1.10-23.45), and 3.29 (1.38-7.88)). Thus, the early postoperative behavior of the pulmonary circulation and systemic inflammatory response are closely related and can be used to predict outcomes in this population.
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    Circulating Levels of RANTES Chemokine Correlate With Pulmonary Hemodynamic Patterns in Pediatric Patients With Congenital Cardiac Communications
    (2018) SOUZA, Maria F.; MAEDA, Nair Y.; CASTRO, Claudia R.; ZORZANELLI, Leina; CLAVE, Mariana M.; LOPES, Antonio A.
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    Prothrombotic Endothelial Dysfunction in Pre-Fontan Subjects is Similar to Pulmonary Arterial Hypertension Associated with the Eisenmenger Syndrome (PAH-Eisenmenger)
    (2012) MAEDA, Nair Y.; SOARES, Rosangela P.; BINOTTO, Maria A.; BYDLOWSKI, Sergio P.; LOPES, Antonio A.
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    Flow-dependent Cardiac Dysfunction and Pressure-dependent Endothelial Activation in Patients With Atrial Septal Defect
    (2013) MAEDA, Nair Y.; COSTA, Henrique G.; SIQUEIRA, Adailson W.; SOARES, Rosangela P.; MESQUITA, Sonia; BYDLOWSKI, Sergio P.; MIURA, Nana; LOPES, Antonio A.
  • article 7 Citação(ões) na Scopus
    Phosphodiesterase type 5 inhibitors improve microvascular dysfunction markers in pulmonary arterial hypertension associated with congenital heart disease
    (2019) CLAVE, Mariana M.; MAEDA, Nair Y.; THOMAZ, Ana M.; BYDLOWSKI, Sergio P.; LOPES, Antonio A.
    Background Ideally, vasodilator therapies for pulmonary arterial hypertension (PAH) should have a favorable impact on markers of vascular dysfunction, in addition to their known effects on hemodynamics, cardiac function, and patient's physical capacity. Methods We analyzed circulating (plasma) markers of endothelial and platelet activation/dysfunction (enzyme-linked immunoassays) in the specific setting of advanced PAH associated with congenital heart disease, during the course of sildenafil and tadalafil therapies. Thirty-one patients were enrolled (age 10-54 years), most of them with chronic hypoxemia and elevated hematocrit. Drugs were administered orally for 6 months (sildenafil [n = 16], 20 mg t.i.d.; tadalafil [n = 15], single daily dose of 40 mg). Measurements were performed at baseline, and 90 and 180 days. Results Compared to controls, patients had elevated baseline beta-thromboglobulin (beta-TG, P = .002), P-selectin (P = .027), tissue-type plasminogen activator (t-PA, P = .009), and von Willebrand factor antigen (VWF:Ag, P = .010). Thrombomodulin was importantly reduced (TM, P < .001), while soluble CD40 Ligand was not changed (P = .320). Tadalafil administration was associated with improvement of beta-TG (P = .004), t-PA (P = .003) and TM (P = .046) levels, while P-selectin was improved by sildenafil treatment only (P = .034). VWF:Ag improved transiently in the sildenafil group (P = .019). Both therapies were associated with improvement of the physical capacity (functional class and distance walked during the 6-minute test, P < .05), hematocrit and hemoglobin level (P < .05), and health-related quality of life (physical and mental components, P < .05). Conclusion In PAH associated with congenital heart disease, phosphodiesterase 5 inhibitors seem to have beneficial actions at microcirculatory level, beyond the proposed effects as vasodilators.
  • article 6 Citação(ões) na Scopus
    Relation of Macrophage Migration Inhibitory Factor to Pulmonary Hemodynamics and Vascular Structure and Carbamyl-Phosphate Synthetase I Genetic Variations in Pediatric Patients with Congenital Cardiac Shunts
    (2019) MAEDA, Nair Y.; AIELLO, Vera D.; SANTOS, Paulo C.; THOMAZ, Ana M.; KAJITA, Luiz J.; BYDLOWSKI, Sergio P.; LOPES, Antonio Augusto
    Macrophage migration inhibitory factor (MIF) plays an important pathophysiological role in pulmonary hypertension (PHT). Previously, we demonstrated that serum MIF is increased in pediatric PHT associated with congenital heart disease (CHD). In the present study, we determined possible associations between MIF levels, hemodynamic and histological parameters, and mitochondrial carbamyl-phosphate synthetase I (CPSI) T1405N polymorphism in a similar population. The asparagine 1405 variant (related to A alleles in the C-to-A transversion) has been shown to be advantageous in pediatric PHT compared to the threonine 1405 variant (C alleles). Forty-one patients were enrolled (aged 2-36 months) and subsequently divided into 2 groups after diagnostic evaluation: the high-pulmonary blood flow (high PBF) group (pulmonary-to-systemic blood flow ratio 2.58 (2.21-3.01), geometric mean with 95% CI) and the high-pulmonary vascular resistance (high PVR) group (pulmonary vascular resistance 6.12 (4.78-7.89) Wood unitsxm2). Serum MIF was measured using a chemiluminescence assay. The CPSI polymorphism was analyzed by polymerase chain reaction followed by high-resolution melting analysis. Medial hypertrophy of pulmonary arteries was assessed by the histological examination of biopsy specimens. Serum MIF was elevated in patients compared to controls (p=0.045), particularly in the high-PVR group (n=16) (p=0.022) and in subjects with the AC CPSI T1405N genotype (n=16) compared to those with the CC genotype (n=25) (p=0.017). Patients with high-PVR/AC-genotype profile (n=9) had the highest MIF levels (p=0.030 compared with the high-PBF/CC-genotype subgroup, n=18). In high-PVR/AC-genotype patients, the medial wall thickness of intra-acinar pulmonary arteries was directly related to MIF levels (p=0.033). There were no patients with the relatively rare AA genotype in the study population. Thus, in the advantageous scenario of the asparagine 1405 variant (AC heterozygosity in this study), heightened pulmonary vascular resistance in CHD-PHT is associated with medial hypertrophy of pulmonary arteries where MIF chemokine very likely plays a biological role.