Systemic PaO2 Oscillations Cause Mild Brain Injury in a Pig Model.
OBJECTIVE
Systemic PaO2 oscillations occur during cyclic recruitment and derecruitment of atelectasis in acute respiratory failure and might harm brain tissue integrity.


METHODS
Controlled animal study.


METHODS
University research laboratory.


METHODS
Adult anesthetized pigs.


METHODS
Pigs were randomized to a control group (anesthesia and extracorporeal circulation for 20 hr with constant PaO2, n = 10) or an oscillation group (anesthesia and extracorporeal circulation for 20 hr with artificial PaO2 oscillations [3 cycles min⁻¹], n = 10). Five additional animals served as native group (n = 5).


RESULTS
Outcome following exposure to artificial PaO2 oscillations compared with constant PaO2 levels was measured using 1) immunohistochemistry, 2) real-time polymerase chain reaction for inflammatory markers, 3) receptor autoradiography, and 4) transcriptome analysis in the hippocampus. Our study shows that PaO2 oscillations are transmitted to brain tissue as detected by novel ultrarapid oxygen sensing technology. PaO2 oscillations cause significant decrease in NISSL-stained neurons (p < 0.05) and induce inflammation (p < 0.05) in the hippocampus and a shift of the balance of hippocampal neurotransmitter receptor densities toward inhibition (p < 0.05). A pathway analysis suggests that cerebral immune and acute-phase response may play a role in mediating PaO2 oscillation-induced brain injury.


CONCLUSIONS
Artificial PaO2 oscillations cause mild brain injury mediated by inflammatory pathways. Although artificial PaO2 oscillations and endogenous PaO2 oscillations in lung-diseased patients have different origins, it is likely that they share the same noxious effect on the brain. Therefore, PaO2 oscillations might represent a newly detected pathway potentially contributing to the crosstalk between acute lung and remote brain injury.
1Department of Anaesthesiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. 2Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria. 3Department of Anaesthesia and Critical Care, University Hospitals, Wuerzburg, Germany. 4Institute of Neuropathology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. 5Core Facility Bioinformatics, Division Biostatistics and Bioinformatics, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany. 6Division Biostatistics and Bioinformatics, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Klaus U
KU
Klein
Amelie
A
Johannes
Melanie
M
Brückner
Rainer
R
Thomas
Stephan
S
Matthews
Katrin
K
Frauenknecht
Petra
P
Leukel
Johanna
J
Mazur
Alicia
A
Poplawski
Ralf
R
Muellenbach
Clemens J
CJ
Sommer
Serge C
SC
Thal
Kristin
K
Engelhard
D000818:Animals; D001784:Blood Gas Analysis; D001930:Brain Injuries / Q000209:etiology* / Q000503:physiopathology*; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism; D001261:Pulmonary Atelectasis / Q000517:prevention & control; D018075:RNA, Complementary / Q000378:metabolism; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D013552:Swine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018836:Inflammation Mediators; D018075:RNA, Complementary; D005680:gamma-Aminobutyric Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid