Effects of postresuscitation N-acetylcysteine on cerebral free radical production and perfusion during reoxygenation of hypoxic newborn piglets.
Hydrogen peroxide (H2O2) and nitric oxide (NO) contribute to the pathogenesis of cerebral hypoxic-ischemic injury. We evaluated the neuroprotective effect of N-acetyl-l-cysteine (NAC, a free radical scavenger) against oxidative stress and perfusion in a model of neonatal hypoxia-reoxygenation (H-R). Piglets (1-3 d, 1.6-2.3 kg) were randomized into a sham-operated group (without H-R) (n = 5) and two H-R experimental groups (2 h normocapnic alveolar hypoxia followed by 4 h reoxygenation) (n = 7/group). Five minutes after reoxygenation, piglets were given either i.v. saline (H-R controls) or NAC (30 mg/kg bolus then 20 mg/kg/h infusion) in a blinded-randomized fashion. Heart rate, mean arterial pressure, carotid arterial blood flow (transit-time ultrasonic probe), cerebral cortical H2O2 and NO production (electrochemical sensor), cerebral tissue glutathione and nitrotyrosine levels (enzyme-linked immunosorbent assay) were examined. Hypoxic piglets were acidotic (pH 6.88-6.90), which recovered similarly in the H-R groups (p > 0.05 versus shams). Postresuscitation NAC treatment significantly attenuated the increase in cortical H2O2, but not NO, concentration during reoxygenation, with lower cerebral oxidized glutathione levels. NAC-treated piglets had significantly higher carotid oxygen delivery and lower cerebral lactate levels than that of H-R controls with corresponding changes in carotid arterial flow and vascular resistance. In newborn piglets with H-R, postresuscitation administration of NAC reduced cerebral oxidative stress and improved cerebral perfusion.
Lee
Tze-Fun
TF
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Tymafichuk
Corinne N
CN
Bigam
David L
DL
Cheung
Po-Yin
PY
D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D002339:Carotid Arteries / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D005609:Free Radicals / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016166:Free Radical Scavengers; D005609:Free Radicals; D007773:Lactates; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D005978:Glutathione; D010100:Oxygen; D000111:Acetylcysteine