PAULINA SANNOMIYA
Projetos de Pesquisa
Unidades Organizacionais
BMF, ICB - Docente
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- 17 beta-Estradiol as a New Therapy to Preserve Microcirculatory Perfusion in Small Bowel Donors(2020) VIEIRA, Roberta Figueiredo; BREITHAUPT-FALOPPA, Ana Cristina; CORREIA, Cristiano Jesus; ARMSTRONG JR., Roberto; COUTINHO-E-SILVA, Raphael dos Santos; FERREIRA, Sueli Gomes; MOREIRA, Luiz Felipe Pinho; SANNOMIYA, PaulinaBackground. Intestine graft viability compromises retrieval in most brain-dead donors. Small bowel transplantation is a complex procedure with worse outcomes than transplantation of other abdominal organs. The hormone 17 beta-estradiol (E2) has shown vascular protective effects in lung tissue of brain death (BD) male rats. Thus, estradiol might be a treatment option to improve the quality of intestinal grafts. Methods. Male Wistar rats were divided into 3 groups (n = 10/group): rats that were trepanned only (sham-operated), rats subjected to rapid-onset BD, and brain-dead rats treated with E2 (280 mu g/kg, intravenous) (BD-E2). Experiments performed for 180 minutes thereafter are included: (a) laser-Doppler flowmetry and intravital microscopy to evaluate mesenteric perfusion; (b) histopathological analysis; (c) real-time polymerase chain reaction of endothelial nitric oxide synthase (eNOS) and endothelin-1; (d) immunohistochemistry of eNOS, endothelin-1, P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 expression; and (e) ELISA for cytokines and chemokines measurement. Results. 17 beta-Estradiol improved microcirculatory perfusion and reduced intestinal edema and hemorrhage after BD. The proportions of perfused small vessels were (mean +/- scanning electron microscope) BD rats (40% +/- 6%), sham-operated rats (75% +/- 8%), and BD-E2 rats (67% +/- 5%) (P= 0.011). 17 beta-Estradiol treatment was associated with 2-fold increase in eNOS protein (P< 0.0001) and gene (P= 0.0009) expression, with no differences in endothelin-1 expression. BD-E2 rats exhibited a reduction in vascular cell adhesion molecule 1 expression and reduced cytokine-induced neutrophil chemoattractant 1 and interleukina-10 serum levels. Conclusions. 17 beta-Estradiol was effective in improving mesenteric perfusion and reducing intestinal edema and hemorrhage associated with BD. The suggestion is that E2 might be considered a therapy to mitigate, at least in part, the deleterious effects of BD in small bowel donors.
- Hypertonic saline reduces cell infiltration into the lungs after brain death in rats(2020) CORREIA, Cristiano de Jesus; SILVA, Raphael dos Santos Coutinho e; SOARES, Rafaela Garcia Ferreira; JR, Roberto Armstrong; RICARDO-DA-SILVA, Fernanda Yamamoto; SANNOMIYA, Paulina; BREITHAUPT-FALOPPA, Ana Cristina; MOREIRA, Luiz Felipe P.Background: Lung transplantation is a treatment method for end stage lung disease, but the availability of donor lungs remains a major constraint. Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion and increased inflammation, leading to pulmonary dysfunction. Hypertonic saline solution (HSS) is a volume expander possessing immunomodulatory effects. This study evaluated the influence of HSS on pulmonary dysfunction and inflammation in a rat model of BD. Methods: BD was induced by inflation of an intracranial balloon catheter. Rats were divided into [1]: Sham, without BD [2]; NS, NaCl treatment (0.9%, 4 mL/kg, i.v.) immediately after BD [3];HSS1, HSS treatment (NaCl 7.5%, 4 mL/kg, i.v.) immediately after BD; and [4] HSS60, HSS treatment 60 min post BD. All groups were analyzed after 360 min. Results: Animals subjected to BD exhibited increased exhaled O-2 and decreased CO2.The number of leukocytes in the lungs was significantly increased in the NS group (p = 0.002) and the HSS treatment was able to reduce it (p = 0.018 and HSS60 = 0.030). In parallel, HSS-treated rats showed reduced levels of ICAM-1 expression, which was increased in the NS compared to Sham group. Lung edema was found increased in the NS group animals compared to Sham and no effect of the HSS treatment was observed. There were no differences among the groups in terms of TNF-alpha, VEGF, and CINC-1 lung concentrations. Conclusions: HSS is capable of reducing inflammatory cell infiltration into the lung after BD induction, which is associated with the reduction of ICAM-1 expression in organ vessels.