The impact of oxidative stress levels on the clinical effectiveness of sivelestat in treating acute lung injury: an electron spin resonance study.
BACKGROUND
Sivelestat, a neutrophil elastase inhibitor, has been used to treat acute lung injury (ALI) with varying levels of clinical success. Variable baseline levels of oxidative stress in patients with ALI have been proposed as one explanation for inconsistent results.


METHODS
Using a bedside electron spin resonance spectrometer, we evaluated electron spin resonance signal intensities of serum ascorbyl free radicals supplemented with dimethyl sulfoxide (AFR/DMSO) in patients with ALI.


RESULTS
We found a positive correlation between AFR/DMSO and ascorbate levels, suggesting that serum AFR/DMSO measurements may serve as a surrogate for real-time assessments of oxidative stress. Levels of AFR/DMSO in patients with ALI were significantly lower than those found in healthy controls. Stratified analyses revealed that baseline AFR/DMSO levels were significantly lower in patients with ALI who failed to respond to sivelestat compared with those who did respond.


CONCLUSIONS
Our results suggest that the clinical efficacy of sivelestat is dependent on baseline oxidative stress levels.
Matsumoto
Shigekiyo
S
Department of Anaesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan. sigekiyo@med.oita-u.ac.jp
Shingu
Chihiro
C
Koga
Hironori
H
Hidaka
Seigo
S
Goto
Koji
K
Hagiwara
Satoshi
S
Iwasaka
Hideo
H
Noguchi
Takayuki
T
Yokoi
Isao
I
D055371:Acute Lung Injury / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives* / Q000097:blood; D004121:Dimethyl Sulfoxide; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019095:Point-of-Care Systems; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C000820:semidehydroascorbic acid; C069195:sivelestat; D005998:Glycine; D003683:Dehydroascorbic Acid; D004121:Dimethyl Sulfoxide