Mechanical versus humoral determinants of brain death-induced lung injury

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. Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to p...

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Published in:PloS one 2017-07, Vol.12 (7), p.e0181899-e0181899
Main Authors: Belhaj, Asmae, Dewachter, Laurence, Rorive, Sandrine, Remmelink, Myriam, Weynand, Birgit, Melot, Christian, Hupkens, Emeline, Dewachter, Céline, Creteur, Jacques, Mc Entee, Kathleen, Naeije, Robert, Rondelet, Benoît
Format: Article
Language:English
Subjects:
Acute Lung Injury - blood
Acute Lung Injury - etiology
Acute Lung Injury - physiopathology
Animals
Apoptosis
Biology and Life Sciences
Blood
Blood pressure
Brain
Brain death
Brain Death - blood
Brain Death - pathology
Brain Death - physiopathology
Brain injury
Capillary pressure
Care and treatment
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cytokines
Death
Dosage and administration
Edema
Female
Gene Expression Regulation
Health aspects
Heme
Hemodynamics
Hypertension
Hypoxia
Immunity, Humoral
Inflammation
Injuries
Intensive care
Interleukin 10
Interleukin 6
Interleukins - metabolism
Intracranial hypertension
Laboratories
Leukocytes (neutrophilic)
Lung - pathology
Lung - physiopathology
Lung diseases
Lungs
Medicine
Medicine and Health Sciences
Methylprednisolone
Mortality
Multivariate Analysis
Nervous system
Nervous system diseases
Neutrophils
Neutrophils - pathology
Oxidative Stress
Oxygen - metabolism
Oxygenase
Partial Pressure
Permeability
Peroxidase - metabolism
Pharmacology
Physiology
Pigs
Psychological aspects
Pulmonary artery
Respiratory distress syndrome
Respiratory Mechanics
Risk factors
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Surgery
Sus scrofa
Thoracic surgery
Tumor Necrosis Factor-alpha - metabolism
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Summary: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. Brain 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. Intracranial 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. Brain 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0181899