title: Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study.
abstract: OBJECTIVE
  Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma.
  
  
  METHODS
  Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined.
  
  
  RESULTS
  Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals.
  
  
  CONCLUSIONS
  The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Instituto do Coração, Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Brazil. biosimas@usp.br
authors.forename: Rafael
authors.initials: R
authors.lastname: Simas
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
authors.forename: José Walber M C
authors.initials: JW
authors.lastname: Cruz
authors.forename: Cristiano de Jesus
authors.initials: Cde J
authors.lastname: Correia
authors.forename: Fernando Luiz
authors.initials: FL
authors.lastname: Zanoni
authors.forename: Maurício
authors.initials: M
authors.lastname: Kase
authors.forename: Laura
authors.initials: L
authors.lastname: Menegat
authors.forename: Isaac Azevedo
authors.initials: IA
authors.lastname: Silva
authors.forename: Luiz Felipe P
authors.initials: LF
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001926:Brain Death / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology*; D018836:Inflammation Mediators / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007970:Leukopenia / Q000097:blood / Q000209:etiology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013152:Splanchnic Circulation / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D003345:Corticosterone