The protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats.
To investigate the effects of treatment with propofol administration at different time point in acute lung injury of endotoxin-induced shock rats.


METHODS
76 male wistar rats were randomly assigned to five groups: A) control group; B) endotoxemic group, receiving intravenous lipopolysaccharide (LPS) 8 mg.kg-1; C) pretreatment group, treated identically to endotoxemic group with the additional administration of propofol (5 mg.kg-1 bolus, followed by infusion at 10 mg.kg-1.h-1) of 1 hr prior to the injection of LPS; D) simultaneously treatment group, treated identically to endotoxemic group with the additional administration of propofol simultaneously with the injection of LPS; E) post-treatment group, which was treated identically to endotoxemic group except for administration of propofol 1 hr after the injection of LPS. PaO2, pH, MAP and survival rate were recorded and plasma NO, TNF-alpha were measured during 5-hr after the injection of LPS. After the rats were killed, lung tissue was sampled to measured expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT), myeloperoxidase (MPO) activity, malondialdehyde (MDA), wet-to-dry lung weight ratio (W/D), and pulmonary permeability index (PPI).


RESULTS
Compared with the endotoxemic group, both the pretreatment and simultaneously treatment groups, significantly improved PaO2, pH, MAP and 5th hour survival rate of rats, and attenuated endotoxin-induced increased iNOSmRNA, NT expression, MPO activity and MDA level in lung tissue, and decreased pulmonary microvascular permeability, TNF-alpha, NO in plasma. But these beneficial efficacies were blunted in the post-treatment group.


CONCLUSIONS
These findings showed that propofol administration may provide protective effects on acute lung injury in endotoxin-induced shock.
Gao
Ju
J
Department of Anesthesiology, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China.
Zeng
Bangxiong
B
Zhou
Luojing
L
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000097:blood; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D015742:Propofol / Q000097:blood / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000187:drug effects / Q000378:metabolism
D018686:Anesthetics, Intravenous; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D009195:Peroxidase; D015742:Propofol