Mechanical versus humoral determinants of brain death-induced lung injury

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.

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death–induced Lung Injury in Pigs

“…Eighteen female 4-month-old pigs were premedicated, anesthetized, and paralyzed following a protocol described previously (19)(20)(21)(22). As previously reported (19)(20)(21)(22)(23), the animals were equipped to measure systemic arterial pressure (Psa), pulmonary arterial pressure (Ppa), occluded Ppa (Ppao), right atrial pressure (Pra), effective pulmonary capillary pressure (Pcap), thermodilution cardiac output, and instantaneous pulmonary blood flow (Q) and Ppa. The animals were ventilated using an FI O 2 of 0.4-1.0 to maintain Sa O 2 .…”

“…The animals were ventilated using an FI O 2 of 0.4-1.0 to maintain Sa O 2 . 90%, a respiratory rate of 12-20 breaths Á min 21 , and a VT of 15-25 ml Á kg 21 to achieve an arterial Pa CO 2 between 35 and 45 mm Hg and a positive end-expiratory pressure between 5 and 8 cm H 2 O (19)(20)(21)(22). Balanced crystalloid-and gelatin-modified solutions were perfused (at 10 ml Á kg 21 Á h 21 ) to maintain Pra between 6 and 8 mm Hg.…”

“…In the present study, we evaluated the effects of tacrolimus administered as a pretreatment in an experimental model of neurogenic pulmonary edema secondary to subdural autologous blood infusion-induced brain death in pigs (19). We focused on the relationship between the expression of inflammatory mediators, endothelial function actors, glycocalyx proteoglycans, and hemodynamic derangements and the development of ALI.…”

The influence of female sex hormones on lung inflammation after brain death ‐ an experimental study

“…Brain death results in the development of a systemic inflammatory response in the donors that is accompanied by an increased cell infiltration to the lungs . In this study, we have compared the effect of brain death in female rats with no ovaries, therefore with very low sex hormone levels, to animals with normal hormonal levels.…”

Estudo dos efeitos do 17Îbeta-estradiol sobre a microcirculação em modelo de morte encefálica em ratos machos

“…O pulmão é particularmente vulnerável aos efeitos deletérios relacionados à morte encefálica. Há lesões inespecíficas como a pneumonia associada à ventilação mecânica e lesões específicas como o edema pulmonar neurogênico, que contribuem para a sua baixa utilização (Avlonitis et al, 2005;Cypel et al, 2011;Zhou et al, 2013;Belhaj et al, 2017).…”