CELSO KIYOCHI TAKIMURA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
26 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 26
- 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.
- Tomografia de coerência óptica broncoscópica(2012) RODRIGUES, Ascedio Jose; TAKIMURA, Celso Kiyochi; LEMOS NETO, Pedro Alves; FIGUEIREDO, Viviane RossiObjective: To evaluate the feasibility of and the potential for using optical coherence tomography in conjunction with conventional bronchoscopy in the evaluation of the airways. Methods: This was a pilot study based on an ex vivo experimental model involving three animals: one adult New Zealand rabbit and two Landrace pigs. An optical coherence tomography imaging catheter was inserted through the working channel of a flexible bronchoscope in order to reach the distal trachea of the animals. images of the walls of the trachea were systematically taken along its entire length, from the distal to the proximal portion. Results: The imaging catheter was easily adapted to the working channel of the bronchoscope. High-resolution images of cross sections of the trachea were taken in real time, precisely delineating microstructures, such as the epithelium, submucosa, and cartilage, as well as the adventitia of the anterior and lateral tracheal walls. The corresponding layers of the epithelium, mucosa, and cartilage were clearly differentiated. The mucosa, submucosa, and trachealis muscle were clearly identified in the posterior wall. Conclusions: It is feasible to use an optical coherence tomography imaging catheter in combination with a flexible bronchoscope. Optical coherence tomography produces high-resolution images that reveal the microanatomy of the trachea, including structures that are typically seen only on images produced by conventional histology.
- Remoção Precoce do Introdutor Arterial Após Intervenção Coronária Percutânea por Via Femoral: Estudo de Segurança e Eficácia(2014) ZAGO, Gabriel; TRENTIN, Fabio; PRADO JR., Guy F. A.; SPADARO, Andre Gasparini; SILVA, Expedito Eustáquio Ribeiro da; CAMPOS, Carlos Magalhães; PERIN, Marco Antonio; FALCÃO, Breno de Alencar Araripe; ESTEVES-FILHO, Antonio; KAJITA, Luiz Junya; GAMA, Marcus Nogueira da; MARCHIORI, Gilberto; HORTA, Pedro Eduardo; TAKIMURA, Celso Kiyochi; MARIANI JR., Jose; GALON, Micheli Zanotti; SOARES, Paulo Rogerio; ZALC, Silvio; KALIL-FILHO, Roberto; LEMOS NETO, Pedro AlvesIntroduction: We evaluated the safety and efficacy of protamine administration, guided by activated clotting time, for the immediate femoral arterial sheath removal in patients undergoing percutaneous coronary intervention with unfractionated heparin in order to propose an algorithm for clinical practice. Methods: Prospective study with consecutive patients with stable angina or low-to-moderate risk acute coronary syndrome. We compared patients with an early removal of the arterial sheath to those whose sheath removal was based on a standard protocol. Results: The early removal group (n = 149) had lower access manipulation time than the conventional group (58.3 ± 21.4 minutes vs. 355.0 ± 62.9 minutes; p < 0.01), mainly due to a reduced time to sheath removal (42.3 ± 21.1 minutes vs. 338.6 ± 61.5 minutes; p < 0.01), with no impact on the duration of femoral compression (16.0 ± 3.6 minutes vs. 16.4 ± 5.1 minutes; p = 0.49). There was no stent thrombosis during hospitalization and no significant differences in the incidence of major vascular or bleeding events. The incidence of other bleeding events leading to a prolonged in-hospital length of stay was lower in the early removal group (1.3% vs. 5.1%; p = 0.05). Conclusions: The selective use of an approach for immediate femoral sheath removal, based on activated clotting time guidance and protamine administration, is a safe and effective option in patients undergoing percutaneous coronary intervention by femoral access.
- Células-tronco de tecido adiposo e a importância da padronização de um modelo animal para experimentação pré-clínica(2013) ZUTTION, Marilia Sanches Santos Rizzo; WENCESLAU, Cristiane Valverde; LEMOS, Pedro A.; TAKIMURA, Celso; KERKIS, IrinaStem cells are undifferentiated cells and can self-renew and differentiate into various cell types, besides having immunomodulating properties and paracrine effects in response to tissue injury, and may therefore treat injuries and diseases or even replace damaged or lost cells. Adipose tissue is an attractive source of adult stem cells, since the human body has a large reserve that is obtained in large amounts by minimally invasive methods. Interest in these cells has been increasing steadily due to their properties and possible applications in regenerative medicine and cell therapy. A large part of these investigations are focused on cardiovascular diseases, which are a leading cause of morbidity and mortality worldwide. Although in recent years treatments have advanced in cardiology, the development of new therapies to recover the damaged tissue still remains one of the main goals of cardiac research. However, to achieve effective results, in vivo and in vitro animal models for preclinical studies and consequently for application in humans must be standardized. The development of preclinical models in large animals requires the use of well-characterized animal cell lines, similar to human cells, and the use of the porcine model represents a great advantage for preclinical translational research.
- Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model(2018) GUIDO, Maria C.; DEBBAS, Victor; SALEMI, Vera M.; TAVARES, Elaine R.; MEIRELLES, Thayna; ARAUJO, Thais L. S.; NOLASCO, Patricia; FERREIRA-FILHO, Julio C. A.; TAKIMURA, Celso K.; PEREIRA, Lygia V.; LAURINDO, Francisco R.Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mg Delta(loxPneo) mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.
- 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.
conferenceObject Rat brain basal ganglia imaged with optical coherence tomography: Feasibility and future perspectives(2015) ANGELOS, J. S. dos; LOPEZ, W. O. C.; MARTINEZ, R. C. R.; REIS, P. R.; TAKIMURA, C. K.; TEIXEIRA, M. J.; LEMOS NETO, P. A.; FONOFF, E. T.conferenceObject A Novel Magnesium Bioresorbable Stent Allows Coronary Vascular Restoration and Positive Remodeling in a Large Animal Model: A Sequential Optical Coherence Tomography Study(2015) TAKIMURA, Celso K.; CAVALCANTI, Rafael R.; GALON, Micheli Z.; ARRIETA, Raul; TELLEZ, Armando; CAMPOS, Carlos M.; CURADO, Luciano; MEYER-KOBBE, Clemens; KRIEGER, Jose E.; LEMOS, Pedro A.- Assessment of Stent Strut Endothelialization in Iliac Arteries of Rabbits(2012) TAKIMURA, Celso Kiyochi; WATANABE, Ii-sei; LAURINDO, Francisco Rafael Martins; GUTIERREZ, Paulo Sampaio; AIELLO, Vera Demarchi; MORATO, Spero Penha; LEMOS NETO, Pedro AlvesBackground: Fast post-implantation stent endothelialization is desirable for theoretically reducing the possibility of stent thrombosis. Objective: To evaluate the extent of sirolimus-eluting stent strut endothelialization (delivered from the luminal and abluminal aspects or abluminal aspect only) in the iliac arteries of rabbits. Methods: The iliac arteries of 10 rabbits were implanted with four sirolimus-eluting stents in the luminal and abluminal aspects, three sirolimus-eluting stents in the abluminal aspect, six polymer-coated stents, and four uncoated stents. After four weeks, the rabbits were euthanized and scanning electron microscopy was performed to quantify the area of exposed stent strut as well as the percentage of endothelialization. Results: The area (mean +/- SD) (mm(2)) of exposed uncoated stent struts, polymer-coated stents, sirulimus-eluting stent in the abluminal and luminal aspects and sirolimus-eluting stent in the abluminal aspect was 0.12 +/- 0.08, 0.09 +/- 0.12, 0.60 +/- 0.67 and 0.05 +/- 0.04, respectively (p = 0.120). The percentage of endothelialization (mean +/- SD) (%) of uncoated stents, polymer-coated stents, sirolimus-eluting stents in the luminal and abluminal aspects and sirolimus-eluting stents in the abluminal aspect was 99 +/- 01, 99 +/- 0. 97 +/- 03 and 99 +/- 0, respectively (p = 0.133). Conclusion: After four weeks of implantation in the iliac arteries of rabbits, both the sirolimus-eluting stents in the luminal plus abluminal aspects and those in the abluminal aspect only showed stent strut endothelialization rates similar to those of the other types of non-drug eluting stents.
- Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter(2013) LEMOS, Pedro A.; FAROOQ, Vasim; TAKIMURA, Celso K.; GUTIERREZ, Paulo S.; VINNANI, Renu; KOLODGIE, Frank; CHRISTIANS, Uwe; KHARLAMOV, Alexander; DOSHI, Manish; SOJITRA, Prakash; BEUSEKOM, Heleen M. M. van; SERRUYS, Patrick W.Drug-eluting stents have proven to be effective in reducing the risk of late restenosis. In order to achieve a controlled and prolonged release of the antiproliferative agent, current drug-eluting stents utilise various biodegradable as well as non-erodible polymeric blends to coat the stent surface and to serve as drug carriers. The utilisation of polymeric compounds in current drug-eluting stents may eventually limit their performance as well as their clinical applicability due to the potential induction of undesirable local reactions. The development of alternative, polymer-free drug carriers has the potential to overcome some of the limitations of current drug-eluting stent formulations. Moreover, improvements in drug carriers may also result in an expansion of the technological possibilities for other intravascular drug delivery systems, such as metal-free or even implant-free solutions. This article describes the structure and the preclinical validation profile of a novel phospholipid encapsulated sirolimus nanocarrier, used as a coating in two formulations: a coronary stent-plus-balloon system and a stand-alone balloon catheter. The nanoparticles provided a stable, even and homogenous coating to the devices in both formulations. Dose-finding studies allowed the most appropriate identification of the best nanoparticle structure associated with an extremely efficient transfer of drug to all layers of the vessel wall, achieving high tissue concentrations that persisted days after the application, with low systemic drug leaks.
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