Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: effects on oxidative stress.
OBJECTIVE
To determine the effects of normoxic vs. hyperoxic resuscitation on oxidative stress in a model of pediatric asphyxial cardiac arrest.


METHODS
Prospective, interventional study.


METHODS
University research laboratory.


METHODS
Postnatal day 16-18 rats (n = 5 per group).


METHODS
Rats underwent asphyxial cardiac arrest for 9 min. Rats were randomized to receive 100% oxygen, room air, or 100% oxygen with polynitroxyl albumin (10 mL·kg⁻¹ intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation. Shams recovered in 100% oxygen or room air after surgery.


RESULTS
Physiological variables were recorded at baseline to 1 hr after resuscitation. At 6 hrs after asphyxial cardiac arrest, levels of reduced glutathione and protein-thiols (fluorescent assay), activities of total superoxide dismutase and mitochondrial manganese superoxide dismutase (cytochrome c reduction method), manganese superoxide dismutase expression (Western blot), and lipid peroxidation (4-hydroxynonenal Michael adducts) were evaluated in brain tissue homogenates. Hippocampal 3-nitrotyrosine levels were determined by immunohistochemistry 72 hrs after asphyxial cardiac arrest. Survival did not differ among groups. At 1 hr after resuscitation, Pao2, pH, and mean arterial pressure were decreased in room air vs. 100% oxygen rats (59 ± 3 vs. 465 ± 46 mm Hg, 7.36 ± 0.05 vs. 7.42 ± 0.03, 35 ± 4 vs. 45 ± 5 mm Hg; p < .05). Rats resuscitated with 100% oxygen had decreased hippocampal reduced glutathione levels vs. sham (15.3 ± 0.4 vs. 20.9 ± 4.1 nmol·mg protein⁻¹; p < .01). Hippocampal manganese superoxide dismutase activity was significantly increased in 100% oxygen rats vs. sham (14 ± 2.4 vs. 9.5 ± 1.6 units·mg protein⁻¹, p < .01), with no difference in protein expression of manganese superoxide dismutase. Room air and 100% oxygen plus polynitroxyl albumin groups had hippocampal reduced glutathione and manganese superoxide dismutase activity levels comparable with sham. Protein thiol levels were unchanged across groups. Compared with all other groups, rats receiving 100% oxygen had increased immunopositivity for 3-nitrotyrosine in the hippocampus and increased lipid peroxidation in the cortex.


CONCLUSIONS
Resuscitation with 100% oxygen leads to increased oxidative stress in a model that mimics pediatric cardiac arrest. This may be prevented by using room air or giving an antioxidant with 100% oxygen resuscitation.
Department of Critical Care Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. karen.walson@choa.org
Karen H
KH
Walson
Minke
M
Tang
Ashley
A
Glumac
Henry
H
Alexander
Mioara D
MD
Manole
Li
L
Ma
Carelton J
CJ
Hsia
Robert S
RS
Clark
Patrick M
PM
Kochanek
Valerian E
VE
Kagan
Hülya
H
Bayr
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000150:complications; D001784:Blood Gas Analysis; D015153:Blotting, Western; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000209:etiology / Q000401:mortality* / Q000628:therapy*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000502:physiology; D010102:Oxygen Inhalation Therapy / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012151:Resuscitation / Q000379:methods* / Q000401:mortality; D018570:Risk Assessment; D013482:Superoxide Dismutase / Q000378:metabolism; D015996:Survival Rate
D013482:Superoxide Dismutase; D010100:Oxygen