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Differential Effects of Brain Death on Rat Microcirculation and Intestinal Inflammation: Female Versus Male

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Abstract

Brain death (BD) affects organs by multiple mechanisms related to hemodynamic effects, hormonal changes, and the systemic inflammatory response, which reduce organ function and viability. BD reduces microcirculatory perfusion in rat mesentery; this disturbance is also observed in the pancreas and lungs. Sex hormones can affect microcirculatory function, altering tissue perfusion and influencing the inflammatory process. Here, we present differences between sexes in the microcirculatory alterations generated by BD and in inflammatory infiltrate. Male, female, and ovariectomized-female Wistar rats were submitted to BD by intracranial balloon catheter sudden inflation. BD was confirmed by maximally dilated and fixed pupils, apnea, absence of reflexes, and a drop in mean arterial pressure. Perfusion and flow of the mesenteric microcirculation were analyzed. Intestinal myeloperoxidase activity and leukocyte infiltration were quantified. ELISA quantified serum estradiol, corticosterone, and inflammatory mediators, whereas expression of eNOS, endothelin, and endothelial adhesion molecule was measured by immunohistochemistry. Male rats presented lower percentages of mesenteric perfused microvessels and reduced blood flow compared to females. The female group presented higher eNOS and endothelin expression. Leukocyte infiltration into intestinal walls was higher in females in comparison to that in males. Moreover, the female group showed higher mesenteric vessel ICAM-1 expression than males, whereas serum TNF-α, IL-1β, and IL-10 levels did not differ between sexes. The high estradiol concentration before BD and high eNOS expression apparently favored the maintenance of microvascular perfusion/flow; however, BD caused an acute reduction of female sex hormone concentration and higher ICAM-1 level; thus, the proinflammatory organ status after BD is favored.

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Funding

This study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (grant no. 2013/20282-0). Luiz Felipe Pinho Moreira is a fellow researcher of the CNPq.

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Authors and Affiliations

  1. Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM/11), Instituto do Coração (Incor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Sueli Gomes Ferreira, Roberto Armstrong-Jr, Guilherme Konishi Kudo, Cristiano de Jesus Correia, Paulina Sannomiya, Ana Cristina Breithaupt-Faloppa & Luiz Felipe Pinho Moreira

  2. Laboratório de Investigação Médica (LIM55), Departamento de Urologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil

    Sabrina Thalita dos Reis

Authors
  1. Sueli Gomes Ferreira
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  2. Roberto Armstrong-Jr
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  3. Guilherme Konishi Kudo
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  4. Cristiano de Jesus Correia
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  5. Sabrina Thalita dos Reis
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  6. Paulina Sannomiya
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  7. Ana Cristina Breithaupt-Faloppa
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  8. Luiz Felipe Pinho Moreira
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Contributions

SGF and ACB-F performed all experiments in collaboration with GKK, RAJr, and CJC. STR conducted the gene expression analysis. ACB–F drafted the manuscript and was advised by PS and LFPM. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ana Cristina Breithaupt-Faloppa.

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Ferreira, S.G., Armstrong-Jr, R., Kudo, G.K. et al. Differential Effects of Brain Death on Rat Microcirculation and Intestinal Inflammation: Female Versus Male. Inflammation 41, 1488–1497 (2018). https://doi.org/10.1007/s10753-018-0794-7

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  • DOI: https://doi.org/10.1007/s10753-018-0794-7

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