RAFAEL SIMAS
Projetos de Pesquisa
Unidades Organizacionais
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
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conferenceObject Bilateral Sympathetic Denervation Improves Left Ventricular Function and Prevents Post-Infarction Chamber Remodeling in Rats(2016) ZANONI, F. L.; MOREIRA, L. F.; SIMAS, R.; SILVA, R. G. da; JATENE, F. B.- Bilateral sympathectomy improves postinfarction left ventricular remodeling and function(2017) ZANONI, Fernando Luiz; SIMAS, Rafael; SILVA, Raphael Grillo da; BREITHAUPT-FALOPPA, Ana Cristina; SILVA, Raphael dos Santos Coutinho e; JATENE, Fabio Biscegli; MOREIRA, Luiz Felipe P.Objectives: To evaluate the influence of bilateral or left sympathectomy on left ventricular remodeling and function after myocardial infarction in rats. Methods: Myocardial infarction was induced in rats by ligation of the left anterior descending coronary. Seven days later, rats were divided into 4 groups: the myocardial infarction, myocardial infarction with left sympathectomy, myocardial infarction with bilateral sympathectomy, and sham groups. After 8 weeks, left ventricular function was evaluated with the use of a pressure-volume conductance catheter under steady-state conditions and pharmacological stress. Infarct size and extracellular matrix fibrosis were evaluated, and cardiac matrix metalloproteinases and myocardial inflammatory markers were analyzed. Results: The myocardial infarction and left sympathectomy group had an increased end diastolic volume, whereas the bilateral sympathectomy group had a mean end-diastolic volume similar to that of the sham group (P <. 002). Significant reduction in ejection fraction was observed in the myocardial infarction and left sympathectomy group, whereas it was preserved after bilateral sympathectomy (P < .001). In response to dobutamine, left ventricular contractility increased in sham rats, rising stroke work, cardiac output, systolic volume, end-diastolic volume, ejection fraction, and dP/dt max. Only bilateral sympathectomy rats had significant increases in ejection fraction (P <. 001) with dobutamine. Fibrotic tissue and matrix metalloproteinase expression decreased in the bilateral sympathectomy group compared to that in the myocardial infarction group (P <. 001) and was associated with left ventricular wall thickness maintenance and better apoptotic markers in noninfarcted myocardium. Conclusions: Bilateral sympathectomy effectively attenuated left ventricular remodeling and preserved systolic function after myocardial infarction induction in rats.
- Intrathecal injection of human umbilical cord blood stem cells attenuates spinal cord ischaemic compromise in rats(2014) JUDAS, Gustavo Ieno; FERREIRA, Sueli Gomes; SIMAS, Rafael; SANNOMIYA, Paulina; BENICIO, Anderson; SILVA, Luiz Fernando Ferraz da; MOREIRA, Luiz Felipe PinhoOBECTIVES: Spinal cord ischaemia with resulting paraplegia remains a devastating and unpredictable complication after thoraco-abdominal aortic surgery. With the advent of stem cell therapy and its potential to induce nervous tissue regeneration processes, the interest in the use of these cells as a treatment for neurological disorders has increased. Human stem cells, derived from the umbilical cord, are one of the strong candidates used in cell therapy for spinal cord injury because of weak immunogenicity and ready availability. We sought to evaluate the use of human umbilical cord blood stem cells (HUCBSCs) to attenuate the neurological effects of spinal cord ischaemia induced by high thoracic aorta occlusion. METHODS: Forty Wistar rats were randomized to receive intrathecal injection of 10 mu l phosphate buffered saline (PBS) solution containing 1 x 10(4) HUCBSCs, 30 min before (Tpre group: n = 10) and 30 min after (Tpos group: n = 10) descending thoracic aorta occlusion by intraluminal balloon during 12 min. Control groups received only PBS solution (Cpre group: n = 10; and Cpos group: n = 10). During a 28-day observational period, motor function was assessed by a functional grading scale (Basso, Beattie and Bresnahan). Segments of thoracolumbar spinal cord specimens were analysed for histological and immunohistochemical assessment for detection and quantification of human haematopoietic cells (CD45(+)) and apoptosis (transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling). RESULTS: Overall mortality was 12 animals (30%). Therefore, the observational sample was composed of 28 animals. All groups showed similar incidence of paraplegia and mortality. The mean motor function scores showed no difference during time between the animals of each group, excepting for the Tpos group, which improved from 8.14 (+/- 8.6) to 14.28 (+/- 9.8) (P < 0.01). A treatment-by-time interaction was detected among animals that received HUCBSCs 30 min after ischaemia, with BBB scores higher from Days 14 to 28 compared with the first observational day with statistical difference (P = 0.01). Number of viable neurons was higher in the Tpos group (P = 0.14) and the incidence of apoptosis was lower in the same animals (P = 0.048), but showed no difference with its respective control. We confirmed the presence of CD45(+) cells 4 weeks after intrathecal injection in both therapeutic groups but mainly in the Tpos group. CONCLUSIONS: Intrathecal transplantation of HUCBSCs is feasible, and it improved spinal cord function, when they were delivered 30 min after spinal cord ischaemia, in a model of endovascular descending thoracic aorta occlusion in rats. Human umbilical cord blood is one of the potentially useful sources of stem cells for therapy of spinal cord ischaemia.
- Acute administration of oestradiol or progesterone in a spinal cord ischaemia-reperfusion model in rats(2018) CAVALCANTE, Leonardo Pessoa; FERREIRA, Sueli Gomes; PEREIRA, Daniel Romano; MORAES, Sergio Rodrigues de; SIMAS, Rafael; SANNOMIYA, Paulina; BREITHAUPT-FALOPPA, Ana Cristina; MOREIRA, Luiz Felipe PinhoOBJECTIVES: Despite research into protective pharmacological adjuncts, paraplegia persists as a dreaded complication after thoracic and thoracoabdominal aortic interventions. Reports on gender-related neurological outcomes after ischaemic and traumatic brain injuries have led to increased interest in hormonal neuroprotective effects and have generated other studies seeking to prove the neuroprotective effects of the therapeutic administration of 17 beta-oestradiol and of progesterone. We hypothesised that acute administration of oestradiol or progesterone would prevent or attenuate spinal cord ischaemic injury induced by occlusion of the descending thoracic aorta. METHODS: Male rats were divided into groups receiving 280 A mu g/kg of 17 beta-oestradiol or 4 mg/kg of progesterone or vehicle 30 min before transitory endovascular occlusion of the proximal descending thoracic aorta for 12 min. Hindlimb motor function was assessed by a functional grading scale (that of Basso, Beattie and Bresnahan) for 14 days after reperfusion. On the 14th day, a segment of the thoracolumbar spinal cord was harvested and prepared for histological and immunohistochemical analyses. RESULTS: There was significant impairment of the motor function of the hindlimb in the 3 study groups, with partial improvement noticed over time, but no difference was detected between the groups. On Day 1 of assessment, the 17 beta-oestradiol group had a functional score of 9.8 (0.0-16.5); the progesterone group, a score of 0.0 (0-17.1) and the control group, a score of 6.5 (0-16.9); on the 14th day, the 17 beta-oestradiol group had a functional score of 18.0 (4.4-19.4); the progesterone group had a score of 7.5 (0-18.5) and the control group had a score of 17.0 (0-19.9). Analysis of the grey matter showed that the number of viable neurons per section was not different between the study groups on the 14th day. Immunostaining of the spinal cord grey matter was also similar among the 3 groups. CONCLUSIONS: Acute administration of oestradiol or of progesterone 30 min before transitory occlusion of the proximal descending thoracic aorta of male rats could not prevent or attenuate spinal cord ischaemic injury based on an analysis of functional and histological outcomes.
conferenceObject Hypertonic Saline Solution Preserves Left Ventricular Function and Inhibit Myocardial Injury Triggered by Brain Death in Rats(2016) MOREIRA, L. F.; MAGALHAES, D. M.; ZANONI, F. L.; CORREIA, C. J.; SIMAS, R.; SANNOMIYA, P.- Effect of bilateral sympathectomy in a rat model of dilated cardiomyopathy induced by doxorubicin(2020) SILVA, Raphael dos Santos Coutinho e; ZANONI, Fernando Luiz; SIMAS, Rafael; SILVA, Mateus Henrique Fernandes Martins da; ARMSTRONG JUNIOR, Roberto; CORREIA, Cristiano de Jesus; FALOPPA, Ana Cristina Breithaupt; MOREIRA, Luiz Felipe PinhoObjective: The study objective was to evaluate the effect of bilateral sympathectomy on ventricular remodeling and function in a rat model of dilated cardiomyopathy induced by doxorubicin. Methods: Dilated cardiomyopathy was induced in male Wistar rats by weekly intraperitoneal injection of doxorubicin (2 mg/kg) for 9 weeks. Animals were divided into 4 groups: dilated cardiomyopathy; bilateral sympathectomy, submitted on day 15 of the protocol to bilateral sympathectomy; angiotensin-converting enzyme inhibitor, treated with enalapril through day 15 until the end of the experimental protocol; and sham, nonsubmitted through doxorubicin protocol, with weekly intraperitoneal injections of saline solution (0.9%). The left ventricular function was assessed, and the heart was collected for posterior analyses. Results: The dilated cardiomyopathy group presented a significant decrease in the myocardial efficiency when compared with the sham group (33.4% vs 71.2%). Only the bilateral sympathectomy group was able to preserve it (57.5%; P = .0001). A significant dilatation in the left ventricular chamber was observed in the dilated cardiomyopathy group (15.9 mu m(2)) compared with the sham group (10.2 mu m(2); P = .0053). Sympathectomy and enalapril prevented ventricular remodeling (9.5 and 9.6 mu m(2), respectively; P = .0034). There was a significant increase in interstitial myocardial fibrosis in the dilated cardiomyopathy group (14.8%) when compared with the sham group (2.4%; P = .0001). This process was significantly reduced with sympathectomy and enalapril (8.7 and 3.9%, respectively; P = .0001). Conclusions: Bilateral sympathectomy was effective in preventing remodeling and left ventricular dysfunction in a rat model of dilated cardiomyopathy induced by doxorubicin.