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.METHOD: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 P-selectin 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.CONCLUSION: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.

Sex-related differences in lung inflammation after brain death

“…The mechanisms involved in donor organ alterations include hemodynamic instability, hormonal changes, and immunologic alterations such as cytokine release and upregulation of adhesion molecules [18]. Previous studies have shown that BD induces microcirculatory hypoperfusion and leads to increased local inflammation and organ dysfunction [19]. Pathophysiological changes have been demonstrated in many transplantable organs [20] and might be responsible for the BD-mediated deterioration of organ function [21,22].…”

Evidence of bone marrow downregulation in brain‐dead rats

“…; Simas et al . ). Second, BD impairs the endocrine system and decreases the release of hormones, such as triiodothyronine (T3), thyroxine (T4), cortisol and anti‐diuretic hormone, thereby suggesting an interruption along the hypothalamic–pituitary–adrenal axis (Pratschke et al .…”

“…; Simas et al . ). Although the release of high levels of catecholamines and adrenal steroids hormones is an essential component of the response to BD, these stress mediators do not have long‐lasting effects, as previously registered in brain‐dead patients and demonstrated in experimental models of BD (Herijgers et al .…”

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“…5 Intubation was performed from tracheostomy cannula, which was previously generated. The second scintigraphy was performed under intubation and monitored.…”