Systemic neutrophil activation and lung injury in the brain-dead donor is a biphasic phenomenon

Abstract

Purpose: Brain death is accompanied by hypertensive crisis followed by hypotension. We examined the role of the haemodynamic changes in the systemic neutrophil activation and lung injury. Procedures: Rats (n 49) were anaesthetised and ventilated. Brain death was induced by intracranial balloon inflation in 37: a) “BD” group (n 13); b) “Phentolamine” group (n 12) received phentolamine before balloon inflation to prevent hypertension; c) “Noradrenaline” group (n 12) received intravenous infusion of noradrenaline after brain death to correct hypotension. In 12 rats (Sham) a balloon was inserted, but not inflated. Arterial blood gases and blood neutrophil CD11b/CD18 were measured for 4 h. Lungs were examined with transmission electron microscopy (TEM). Results: In BD, balloon inflation increased mean arterial pressure (MAP) to 150 14.5 mmHg (p 0.001). MAP then fell to a hypotensive plateau (p 0.001). In Phentolamine, the drug decreased MAP by 31 6.9%. Subsequent balloon inflation increased MAP, but not higher than Sham levels (p 0.8). MAP then fell to a plateau, similar to BD (p 0.4). In Noradrenaline, plateau MAP was increased to Sham levels (p 0.3). The BD group had significant metabolic acidosis (MA)(p 0.001), increased alveolo-arterial difference in partial oxygen pressure (P[A-a]O2)(p 0.036) and higher neutrophil CD11b/CD18 levels (p 0.01), compared with Sham. In Phentolamine, P[A-a]O2 and CD18 were similar to Sham, but MA was worse (p 0.001) and CD11b was higher (p 0.049). In Noradrenaline, all variables were similar to Sham (p 0.05). TEM revealed areas of full-thickness capillary-alveolar membrane rupture in BD and Noradrenaline. Lungs from Sham and Phentolamine were normal. Conclusions: The hypertensive crisis associated with brain death can cause stress failure of the pulmonary capillaries, neutrophil activation and lung dysfunction in the transplant donor, which are blocked by phentolamine. Further neutrophil activation and lung injury can be induced by neurogenic hypotension and organ ischaemia, and are reversed by noradrenaline. Optimal donor management requires control of both phases.