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 alpha-
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.