N-acetylcysteine improves hemodynamics and reduces oxidative stress in the brains of newborn piglets with hypoxia-reoxygenation injury.
Reactive oxygen species have been implicated in the pathogenesis of hypoxic-ischemic injury. It has been shown previously that treating an animal with N-acetyl-L-cysteine (NAC), a scavenger of free radicals, significantly minimizes hypoxic-ischemic-induced brain injury in various acute models. Using a subacute swine model of neonatal hypoxia-reoxygenation (H-R), we evaluated the long-term beneficial effect of NAC against oxidative stress-induced brain injury. Newborn piglets were randomly assigned to a sham-operated group (without H-R, n = 6), and two H-R experimental groups (n = 8 each), with 2 h normocapnic alveolar hypoxia and 1 h of 100% oxygen reoxygenation followed by 21% oxygen for 47 h. Five minutes after reoxygenation, the H-R piglets received either normal saline (H-R controls) or NAC (150 mg/kg bolus and 20 mg/kg/h IV for 24 h) in a blinded randomized fashion. Treating the piglets with NAC significantly increased both common carotid arterial flow (CCAF) and oxygen delivery during the early phase of rexoygenation, while both CCAF and carotid oxygen delivery of the H-R group remained lower than the sham-operated groups throughout the experimental period. Compared with H-R controls, significantly higher amounts of anesthetic and sedative medications were required to maintain the NAC-treated piglets in stable condition throughout the experimental period, indicating a stronger recovery. Post-resuscitation NAC treatment also significantly attenuated the increase in cortical caspase-3 and lipid hydroperoxide concentrations. Our findings suggest that post-resuscitation administration of NAC reduces cerebral oxidative stress with improved cerebral oxygen delivery, and probably attenuates apoptosis in newborn piglets with H-R insults.
Liu
Jiang-Qin
JQ
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Lee
Tze-Fun
TF
Chen
Chao
C
Bagim
David L
DL
Cheung
Po-Yin
PY
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003553:Cystine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D013552:Swine
D008054:Lipid Peroxides; D019344:Lactic Acid; D003553:Cystine; D053148:Caspase 3; D005978:Glutathione; C030905:N-monoacetylcystine