The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor.
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.
Avlonitis
Vassilios S
VS
School of Surgical and Reproductive Sciences, Medical School, University of Newcastle, Newcastle upon Tyne, UK. avlonitis@hotmail.com
Wigfield
Christopher H
CH
Kirby
John A
JA
Dark
John H
JH
D000138:Acidosis; D000818:Animals; D001794:Blood Pressure; D001926:Brain Death; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D014019:Tissue Donors
D039481:CD11b Antigen; D018821:CD18 Antigens; D016207:Cytokines