Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys

PURPOSE:To evaluate histopathological alterations triggered by brain death and associated trauma on different solid organs in rats. METHODS: Male Wistar rats (n=37) were anesthetized with isoflurane, intubated and mechanically ventilated. A trepanation was performed and a balloon catheter inserted into intracraninal cavity and rapidly inflated with saline to induce brain death. After induction, rats were monitored for 30, 180, and 360 min for hemodynamic parameters and exsanguinated from abdominal aorta. Heart, lung, liver, and kidney were removed and fixed in paraffin to evaluation of histological alterations (H&E). Sham-operated rats were trepanned only and used as control group. RESULTS: Brain dead rats showed a hemodynamic instability with hypertensive episode in the first minute after the induction followed by hypotension for approximately 1 h. Histological analyses showed that brain death induces vascular congestion in heart (p<0.05), and lung (p<0.05); lung alveolar edema (p=0.001), kidney tubular edema (p<0.05); and leukocyte infiltration in liver (p<0.05). CONCLUSIONS: Brain death induces hemodynamic instability associated with vascular changes in solid organs and compromises most severely the lungs. However, brain death associated trauma triggers important pathophysiological alterations in these organs. Key words: Brain Death. Craniocerebral Trauma. Pathology. Rats. RESUMO OBJETIVO:Avaliar as alterações histopatológicas desencadeadas pela morte encefálica e pelo trauma associado em diferentes órgãos sólidos em ratos. MÉTODOS: Ratos Wistar machos (n=37) foram anestesiados com isoflurano, entubados e mecanicamente ventilados. Foi realizada trepanação e um cateter foi inserido na cavidade intracraniana e insuflado rapidamente para induzir morte encefálica. Após a indução, os ratos foram monitorados por 30, 180 e 360 min para parâmetros hemodinâmicos e exsanguinados pela aorta abdominal. Coração, pulmão, fígado e rim foram removidos e fixados em parafina para avaliação de alterações histológicas (H&E). Ratos falso-operados foram apenas trepanados e usados como grupo controle. RESULTADOS: Ratos com morte encefálica apresentaram instabilidade hemodinâmica com episódio hipertensivo no primeiro minuto após a indução seguido de hipotensão por aproximadamente 1 hora. Análises histológicas demonstraram que a morte encefálica induz congestão vascular no coração (p<0,05) e pulmão (p<0,05); edema alveolar (p=0,001); edema tubular (p<0,05); e infiltrado leucocitário no fígado (p<0,05). CONCLUSÕES: A morte encefálica induz instabilidade hemodinâmica associada com mudanças vasculares em órgãos sólidos e compromete mais severamente os pulmões. Contudo, o trauma associado à morte encefálica desencadeia importantes alterações fisiopatológicas naqueles órgãos. Descritores: Morte Encefálica. Traumatismos Craniocerebrais. Patologia. Ratos.Simas R et al.

show abstract

“…In another study on kidney histology, van der Hoven et al 13 found similar results to those observed previously on liver,…”

supporting

confidence: 78%

Influence of brain death and associated trauma on solid organ histological characteristics

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Donor optimization resulted in better kidney and liver function, but did not inhibit the inflammatory and immunological response in the liver, which increased progressively with time (26). In a similar study from the same group, maintaining donor normotension was found to delay progression of immunological activation in the kidneys (44). The authors suggested that the inflammatory response after brain death is a progressive phenomenon and that time to organ procurement should be kept as short as possible.…”

Section: Discussionmentioning

confidence: 85%

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Avlonitis

Wigfield

Kirby

et al. 2005

American Journal of Transplantation

156

123

View full text Add to dashboard Cite

Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by a -adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.

show abstract

“…Sham-operated rats remained ventilated and anesthetized for half an hour, and then sacrificed. In previous studies, additional controls have been considered; sham animals kept under anesthesia for 4-6 h or hemodynamically unstable non brain-dead animals had only minimal upregulation of pro-inflammatory markers (18).…”

Section: Animals and Experimental Protocolsmentioning

confidence: 99%

Early Events in Kidney Donation: Progression of Endothelial Activation, Oxidative Stress and Tubular Injury After Brain Death

Morariu

Schuurs

Leuvenink

et al. 2008

American Journal of Transplantation

Self Cite

View full text Add to dashboard Cite

Cerebral injury leading to brain death (BD) causes major physiologic derangements in potential organ donors, which may result in vascular-endothelial activation and affect posttransplant graft function. We investigated the kinetic of pro-coagulatory and proinflammatory endothelial activation and the subsequent oxidative stress and renal tubular injury, early after BD declaration. BD was induced by slowly inflating a balloon-catheter inserted in the extradural space over a period of 30 min. Rats (n = 30) were sacrificed 0.5, 1, 2 or 4 h after BD-induction and compared with sham-controls. This study demonstrates immediate pro-coagulatory and pro-inflammatory activation of vascular endothelium after BD in kidney donor rats, proportional with the duration of BD. E-and P-Selectins, Aa /Bb -fibrinogen mRNA were abruptly and progressively up-regulated from 0.5 h BD onwards; P-Selectin membrane protein expression was increased; fibrinogen was primarily visualized in the peritubular capillaries. Plasma von Willebrand factor was significantly higher after 2 h and 4 h BD. Urine heart-fatty-acid-binding-protein and Nacetyl-glucosaminidase, used as new specific and sensitive markers of proximal and distal tubular damage, were found significantly increased after 0.5 h, with a maximum at 4 h. Unexpectedly, oxidative stress was detectable only late, after the installation of tubular injury, suggesting only a secondary role for hypoxia in triggering these injuries.

show abstract

Relationship between duration of brain death and hemodynamic (in)stability on progressive dysfunction and increased immunologic activation of donor kidneys

Cited by 129 publications

References 29 publications

Influence of brain death and associated trauma on solid organ histological characteristics

Influence of brain death and associated trauma on solid organ histological characteristics

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Early Events in Kidney Donation: Progression of Endothelial Activation, Oxidative Stress and Tubular Injury After Brain Death

Contact Info

Product

Resources

About