ANTONIO AUGUSTO BARBOSA LOPES
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina
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- 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 AugustoBackgroundPulmonary 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.
conferenceObject 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.- 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 AugustoThere 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.
- Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics(2022) CARVALHO, Eloisa Sassa; SOUZA, Maria Francilene S.; ABUD, Kelly Cristina O.; CASTRO, Claudia R. P.; PENHA, Juliano G.; THOMAZ, Ana Maria; GUIMARAES, Vanessa A.; LOPES, Antonio AugustoBackground: Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications. Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies. Methods: We analyzed a prospective cohort of 52 pediatric patients (age 3 to 35 months) looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery, defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography. This corresponds to a mean pulmonary arterial pressure of >20 mmHg. Clinical, echocardiographic and hemodynamic parameters were investigated. Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters. Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio (PAP/SAP) obtained per patient during the first 6 h of postoperative care. Results: Among the factors that were investigated as possible predictors, perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis (p < 0.030). Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass (r = 0.70, p < 0.001), and it was higher in subjects with Down syndrome than in nonsyndromic individuals (p = 0.003). Early postoperative PAP/SAP was the only predictor selected using multivariate analysis. It was characterized as an independent predictor after adjustments for possible confounders. An early postoperative PAP/SAP of >0.35 was 76% sensitive and 74% specific at predicting a systolic pulmonary arterial pressure of >30 mmHg 6 months after surgery (hazard ratio with 95% CI 8.972 [2.428-33.158], p = 0.002). Conclusion: The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome, and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.
- Macrophage migration inhibitory factor and chemokine RANTES in young pediatric patients with congenital cardiac communications: Relation to hemodynamic parameters and the presence of Down syndrome(2020) SOUZA, Maria Francilene S.; CARVALHO, Eloisa S.; MAEDA, Nair Y.; THOMAZ, Ana M.; ZORZANELLI, Leina; CASTRO, Claudia R.; PEREIRA, Juliana; LOPES, Antonio AugustoInflammation and immunity are central in the pathobiology of pulmonary vascular disorders. Preliminary headway has been made in understanding the relationships between inflammatory proteins and clinical parameters in pediatric congenital heart disease. In this study, we analyzed serum levels of macrophage migration inhibitory factor (MIF) and regulated on activation normal T cell expressed and secreted chemokine (RANTES) in 87 patients with unrestrictive congenital cardiac communications and signs of pulmonary hypertension (age 2-36 months) and 50 pediatric controls. They were investigated in relation to clinical and hemodynamic parameters and the presence of Down syndrome. Hemodynamics was assessed by transthoracic Doppler echocardiography and cardiac catheterization. Chemokines were analyzed in serum using a chemiluminescence assay. The highest MIF levels were observed in very young subjects with heightened pulmonary vascular resistance but who presented a positive response to vasodilator challenge with inhaled nitric oxide. In contrast, RANTES levels were higher in patients with pulmonary overcirculation and congestion, correlating nonlinearly with pulmonary blood flow. Levels of both chemokines were higher in subjects with Down syndrome than in nonsyndromic individuals, but the difference was observed only in patients, not in the control group. In patients with Down syndrome, there was a direct relationship between preoperative serum MIF and the level of pulmonary artery pressure observed 6 months after surgical repair of cardiac anomalies. Thus, it was interesting to observe that MIF, which is key in the innate immune response and chemokine RANTES, which is highly expressed in respiratory viral infections were related to clinical and hemodynamic abnormalities associated with pediatric congenital heart disease.