Effects of Post-Resuscitation Normoxic Therapy on Oxygen-Sensitive Oxidative Stress in a Rat Model of Cardiac Arrest.

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post-resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen-sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia-induced oxidative stress. Methods and Results Sprague-Dawley rats were subjected to 10-minute asphyxia-induced CA with a fraction of inspired O of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, <0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, <0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, <0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, <0.01). After CA, mitochondrial reactive oxygen species increased by ≈2-fold under hyperoxia. Heme oxygenase expression was also oxygen-sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB-1 (high mobility group box-1) protein was not oxygen-sensitive and was induced by CA. Conclusions Post-resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post-CA organ injury, oxygen metabolism, and survival. Additionally, post-CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.