PAULO SAMPAIO GUTIERREZ
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
38 resultados
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- Modelo porcino para avaliação e desenvolvimento de diferentes dispositivos coronários baseados em cateter: ferramenta pré-clínica fundamental(2013) GALON, Micheli Zanotti; TAKIMURA, Celso Kiyochi; CHAVES, Márcio J. Figueira; CAMPOS, Julliana Carvalho de; KRIEGER, J. Eduardo; GUTIERREZ, Paulo Sampaio; LAURINDO, Francisco Rafael Martins; KALIL FILHO, Roberto; LEMOS NETO, Pedro AlvesBACKGROUND: The experimental porcine model is anatomically and physiologically similar to the human heart, it is easily reproducible and very useful to test new stent and balloon generations. This study was aimed at analyzing an experimental model to evaluate different coronary devices for percutaneous coronary intervention. METHODS: We evaluated 131 juvenile commercial farm pigs, 109 were female, weighing 26.4 ± 3.2 kg. They were anesthetized and had mechanical ventilation and monitoring. Vascular access was obtained via the femoral artery by dissection or puncture. The coronary device was used after a selective catheterization of the coronary arteries with a JR 6 F catheter. Animals were maintained on mechanical ventilation until recovery and were submitted to angiographic evaluation 7, 28, 90 and/or 180 days after the procedure. After euthanasia, the hearts were collected and submitted to macro and microscopic analysis. RESULTS: Six drug-eluting stents, two drug-eluting balloons and two bare-metal stents were tested. Unplanned deaths were observed in 1.5% of the cases during the procedures and in 9.2% of the cases after the procedure, occurring within 12 hours to 6 days (2.3 ± 1.6 days). In addition to angiographic evaluations, intravascular ultrasound and optical coherence tomography were performed during the procedures in 20% and 60% of the cases, respectively. There was no deaths related to the use of the devices. CONCLUSIONS: The experimental percutaneous porcine model proved to be reproducible with similar outcomes and low mortality for the different devices tested and is an essential tool for the evaluation of new coronary devices.
- Male gender and smoking are related to single, but not to multiple, human aortic aneurysms(2015) GUTIERREZ, Paulo S.; LEITE, Thiago N. P.; MANGIONE, Fernanda M.There is scanty information concerning multiple aortic aneurysms. Thus, we verified if clinical or pathological characteristics are different in patients with multiple (two or more) aortic aneurysms in comparison with those with only one. Material and methods: We selected at the necropsy files of the Heart Institute, Sao Paulo University School of Medicine, the last 100 cases with aortic aneurysms, comparing between the two groups: sex, age, presence of systemic arterial hypertension, diabetes, dyslipedemia, history of smoking habit, cause of the aneurysm, cause of death, and if the diagnosis was reached during life. Age was analysed by Mann-Whitney test, and the other variables by chi-square or Fisher's exact test. Results: Multiple aneurysms corresponded to 14% of cases. The proportion of women among patients with multiple aneurysms was higher than among those with single aneurysm(64.3% versus 20.9%, P<.01), even if only cases with atherosclerosis were taken into consideration (women among multiple-6/10, 60.0%; among single-14/70, 20.0%; P=.01). Smoking was less reported in cases with multiple (4/14, 28.6%) than with single aneurysm (53/86, 61.6%; P=.04); considering cases with atherosclerosis, such difference decreases (40.0% of multiple versus 68.6% of single, P=.09). Conclusion: although atherosclerosis is present in most cases of both single and multiple aortic aneurysms, male gender and smoking, considered highly influential in such lesions, are less frequent in patients with multiple than in patients with single aneurysms. Thus mechanisms underlying multiple aortic aneurysms are probably different from those related to single, more common aneurysms.
- Transforming growth factor-beta 1 SMAD effectors and medial cell number in ascending aorta diseases(2016) APARECIDA-SILVA, Rosemeire; BORGES, Luciano Figueiredo; KESSLER, Ketty; DIAS, Ricardo Ribeiro; MOREIRA, Luiz Felipe Pinho; KALIL, Jorge; GUTIERREZ, Paulo SampaioIn ascending aorta aneurysms and dissections, the extracellular matrix is degraded. Transforming growth factor (TGF)-beta 1 modulates its synthesis. The production and presence of SMADs, intracellular effectors of TGF-beta 1 signaling, were analyzed in patients with these diseases. To verify whether medial cells are lost, their total numbers were computed. Ascending aorta samples from 19 patients and 18 controls underwent immunoperoxidase reactions to SMADs 2, 3, 4, and 7. Positive and negative cells were counted, and total numbers of cells and positive/total ratios were calculated. Samples from other 14 patients and 7 normal controls were used for the quantification of SMAD3, SMAD4, and SMAD7 mRNA. For SMAD4, both mRNA (2.36 vs. 0.37, P=. 03) and ratio of positive cells (0.94 vs. 0.73, P=. 02) are increased in patients with ascending aortic diseases. SMAD3 mRNA was also increased (1.19 vs. 0.20, P=. 05). The cell ratios of this and the other SMADs, SMAD7 mRNA, and the total cell count did not differ between groups. In conclusion, in ascending aortic aneurysms and dissections, there is an increase in SMAD4, implicated in extracellular matrix production, possibly as an attempt to compensate for extracellular matrix deficiency. Lost medial cells are replaced, since their number is not diminished.
- Case 3/2017-A 47-Year-Old Female with Refractory Heart Failure and Embolic Acute Myocardial Infarction(2017) LAGE, Joao Gabriel Batista; GUTIERREZ, Paulo SampaioThe patient was a 47-year-old white single female referred for medical treatment to the Instituto do Coracao, born and coming from the state of Sao Paulo, with four children, unemployed, but reporting having worked in coffee farming in inner Minas Gerais state. At the time of her first medical consultation (September 25, 2015), she reported dyspnea on minimal exertion, orthopnea and anasarca, which had started 2 months earlier. She denied angina pectoris, previous myocardial infarction and syncope. She knew she had systemic arterial hypertension and diabetes mellitus, and was being treated at a basic health unit. She used to smoke (20 packs/year), but quit the habit 2 months before. She denied consuming alcoholic beverages and illicit drugs, as well as a family history of cardiovascular disease. She was on metformin (2550 mg/day), furosemide (80 mg/day), carvedilol (12.5 mg/day), and losartan (50 mg/day). On her first medical consultation, her physical exam showed regular general condition and dyspnea in the horizontal position. Her blood pressure was 100/70 mmHg, and heart rate, 102 bpm. Her pulmonary auscultation revealed no respiratory sound on the base of the right lung and no rales. Her cardiac auscultation showed regular gallop rhythm, due to the presence of the third heart sound, and no murmur. Her abdomen was globose, tense, painless, with signs of huge ascites. Her extremities were cold and edematous (++/4+), with symmetrical pulses. The electrocardiogram on the medical consultation showed sinus rhythm, heart rate of 97 bpm, left atrial overload and indirect signs of right atrial overload (Penaloza-Tranchesi sign), low voltage of the QRS complexes in the frontal plane and no progression of the R wave in V-1 to V-4 (probable electrically inactive area in the anterior wall), and diffuse changes of ventricular repolarization (Figure 1). Her chest X-ray showed bilateral veiling of costophrenic sinus, with pleural effusion up to half of the right hemithorax, normal aorta and global heart enlargement (++++/4+) (Figure 2).
- Short-Term Effects of Hydroxyethylstarch Resuscitation on Systemic and Regional Hemodynamics and Metabolism in a Brain-Dead Canine Model(2011) LUCA, Fabio A. De; GARRIDO, Alejandra Gallardo; PRIST, Ricardo; GUTIERREZ, Paulo Sampaio; ROCHA-E-SILVA, Mauricio; CRUZ JR., Ruy J.Background. Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. Methods. Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33mL/kg), and HES (6% HES 450/0.7, 17mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. Results. Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. Conclusion. Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.
- Fibrosis, myocardial crossings, disconnections, abrupt turns, and epicardial reflections: do they play an actual role in human permanent atrial fibrillation? A controlled necropsy study(2013) OLIVEIRA, Italo Martins de; OLIVEIRA, Barbara Daniela; SCANAVACCA, Mauricio Ibrahim; GUTIERREZ, Paulo SampaioAtrial myocardium fibrosis and other alterations of fiber continuity and potential circuit reentrancy (disconnections, abrupt turns, crossings, and epicardial reflections) are thought to play an important role in permanent atrial fibrillation. However, few studies have been performed in human beings. Some of them are only descriptive, and controls were usually normal hearts; thus, differences between cases and controls could be related to the underlying disease rather than the arrhythmia. We quantified by histomorphometry the above characteristics in nine samples (three from the left atrium, three from around fat pads, one from the right atrium, one from the cavum-tricuspid isthmus, and one from the ventricular septum) from 13 necropsy hearts of patients with permanent atrial fibrillation and compared the findings with those from 13 control cases with the same diseases but without any atrial arrhythmia. Statistical analysis was performed using generalized estimating equations and a normal linear mixed model for repeated measures, with significance defined as P <=.05. No differences were found in fibrosis (estimated as collagen/(collagen +myocardium) ratio-0.26 vs. 0.23, P=.35), the presence of disconnections (70.1 vs. 61.5, P=.09), abrupt turns (43.6 vs. 45.3, P=.84), or epicardial reflections (9.4 vs. 14.5, P=.12). The only difference identified was that cases with permanent atrial fibrillation exhibited fewer crossings than those without (79.5 vs. 91.5, P=.02). In conclusion, alterations in myocardial fiber continuity, including fibrosis, seem to reflect a generalized myocardial disorganization of the atria in cardiac disease but are not specifically related to permanent atrial fibrillation.
- Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect(2016) TANAKA, Leonardo Y.; ARAUJO, Haniel A.; HIRONAKA, Gustavo K.; ARAUJO, Thais L. S.; TAKIMURA, Celso K.; RODRIGUEZ, Andres I.; CASAGRANDE, Annelise S.; GUTIERREZ, Paulo S.; LEMOS-NETO, Pedro Alves; LAURINDO, Francisco R. M.Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (approximate to 25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to impaired viscoelastic ductility. Total and PDI-associated expressions of 1-integrin, and levels of reduced cell-surface 1-integrin, were diminished after PDI antibody treatment, implicating 1-integrin as a likely pecPDI target during vessel repair. Indeed, focal adhesion kinase phosphorylation, a downstream 1-integrin effector, was decreased by PDI antibody. Thus, the upregulated pecPDI pool tunes matrix/cytoskeleton reshaping to counteract inward remodeling in vascular pathophysiology.
- Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study(2023) PIRES, Lucas T.; ROSA, Vitor E. E.; MORAIS, Thamara C.; BELLO, Juliana H. S. M.; FERNANDES, Joao R. C.; SANTIS, Antonio de; LOPES, Mariana P.; GUTIERREZ, Paulo S.; ROCHITTE, Carlos E.; NOMURA, Cesar H.; POMERANTZEFF, Pablo M. A.; SAMPAIO, Roney O.; TARASOUTCHI, FlavioAims Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. Methods and results Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m(2); AS: 86 vs. 68 g/m(2), both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m(2) vs. 22 mL/m(2), P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m(2), AS: 22-18.2 mL/m(2), both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m(2) vs. AS: 18.2 mL/m(2), P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). Conclusion Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.
- Cardiac Autonomic Nervous System Remodeling May Play a Role in Atrial Fibrillation: A Study of the Autonomic Nervous System and Myocardial Receptors(2021) OLIVEIRA, Italo Martins de; SILVA JR., Evilasio Leobino da; MARTINS, Yasmin de Oliveira; ROCHA, Hermano Alexandre Lima; SCANAVACCA, Mauricio Ibrahim; GUTIERREZ, Paulo SampaioBackground: The primary factors that originate and perpetuate atrial fibrillation (AF) are electrical and anatomical substrate alterations. However, the central mechanisms governing AF perpetuation have not been elucidated yet, which is reflected on the modest results of the treatment in patients with long persistent AF. Objective: To evaluate if human intrinsic cardiac autonomic nervous system (ICANS) remodeling, including nervous system fibers and muscarinic and beta-adrenergic receptors, play a role in permanent AF. Methods: Heart necropsy samples from thirteen patients with heart disease and permanent AF and thirteen controls without AF were used. By using immunoperoxidase and histomorphometry quantification, we identified the following: the density of all fibers of the ICANS, sympathetic and parasympathetic fibers; and the percentage of myocardium positive for beta-adrenergic receptors 1, 2 and 3; G protein-coupled receptor kinase-5 (GRK-5); and muscarinic receptors M1 to M5. The results were compared using ANOVA and nested ANOVA and were adjusted according to the left atrium volume for all variables, and beta-blocker use to evaluate the expression of beta-receptors and GRK-5. Results: There was an overall increase in the density of fibers of the ICANS (p=0.006), especially in atrial sympathetic nerve fibers (p=0.017). Only M1 muscarinic receptors were increased (5.87 vs 2.35, p=0.032). For adrenergic receptors, the results were positive for increased expression of beta-3 (37.41 vs 34.18, p=0.039) and GRK-5 (51.16 vs 47.66; p<0.001). beta-blocker use had no impact on beta-receptor expression. Conclusion: Increased ICANS innervation and remodeling receptor expression in regions prone to triggering AF may play a role in permanent AF.
- Associations between clinical features and therapy with macrophage subpopulations and T cells in inflammatory lesions in the aorta from patients with Takayasu arteritis(2020) SANTOS, J. P. dos; NETO, R. Artigiani; MANGUEIRA, C. L. P.; FILIPPI, R. Z.; GUTIERREZ, P. S.; WESTRA, J.; BROUWER, E.; SOUZA, A. W. S. deTakayasu arteritis (TAK) is a large-vessel granulomatous vasculitis; the inflammatory infiltration in arteries comprises macrophages, multi-nucleated giant cells, CD4(+)and CD8(+)T cells, gamma delta T cells, natural killer (NK) cells and neutrophils. However, it is unknown which subtype of macrophages predominates. This study aims to evaluate macrophages subpopulations in the aorta in TAK. Immunohistochemistry was performed in the aorta from TAK patients (n = 22), patients with atherosclerotic disease (n = 9) and heart transplant donors (n = 8) using the markers CD68, CD86, CD206, CD3, CD20 and CD56. Active disease was observed in 54 center dot 5% of patients and active histological lesions were found in 40 center dot 9%. TAK patients presented atherosclerotic lesions in 27 center dot 3% of cases. The frequency of macrophages, M1 macrophages, T, B and NK cells was higher in the aorta from TAK and atherosclerotic patients compared to heart transplant donors. In TAK, macrophages and T cells were the most abundant cells in the aorta, and the expression of CD206 was higher than CD86 (P = 0 center dot 0007). No associations were found between the expression of cell markers and active disease or with atherosclerotic lesions. In TAK patients, histological disease activity led to higher T cell counts than chronic fibrotic lesions (P = 0.030), whereas prednisone use was associated with lower T cell counts (P = 0 center dot 035). In conclusion, M1 macrophages were more frequent in TAK and atherosclerotic patients compared to heart transplant donors, while M2 macrophages dominated M1 macrophages in TAK. T cells were associated with histological disease activity and with prednisone use in TAK.