Abstract
BackgroundThe mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations.MethodsBrain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury.ResultsIntracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score.ConclusionsBrain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone.
Highlights
Brain death (BD) induced lung injury called neurogenic pulmonary edema (NPE) is an acute condition which follows closely a variety of insults to the central nervous system that cause acute, rapid, abrupt and extreme increase in intracranial pressure (ICP) [1,2,3]
Intracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in pulmonary artery pressure (PAP), pulmonary capillary pressure (PCP) and the venous component of pulmonary vascular resistance (PVR), while pulmonary artery wedge pressure (PAWP) did not change
Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/interleukin 10 (IL-10) ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression
Summary
Brain death (BD) induced lung injury called neurogenic pulmonary edema (NPE) is an acute condition which follows closely a variety of insults to the central nervous system that cause acute, rapid, abrupt and extreme increase in intracranial pressure (ICP) [1,2,3]. The pathophysiology linking the neurologic, cardiac, and pulmonary conditions in NPE remains debated. In the neuro-cardiac theory, the catecholamines storm following the neurologic insult leads to direct toxic myocardial injury as described in the Takotsubo’s cardiomyopathy and the development of pulmonary edema [5]. The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations
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