Background Hyperoxia during cardiopulmonary resuscitation (CPR) may lead to oxidative injury from mitochondrial-derived reactive oxygen species, despite guidelines recommending 1.0 inspired oxygen during CPR. We hypothesized exposure to 1.0 inspired oxygen during CPR would result in cerebral hyperoxia, higher mitochondrial-derived reactive oxygen species, increased oxidative injury, and similar survival compared with those exposed to 21% oxygen. Methods and Results Four-week-old piglets (n=25) underwent asphyxial cardiac arrest followed by randomization and blinding to CPR with 0.21 (n=10) or 1.0 inspired oxygen (n=10) through 10 minutes post return of spontaneous circulation. Sham was n=5. Survivors received 4 hours of protocolized postarrest care, whereupon brain was obtained for mitochondrial analysis and neuropathology. Groups were compared using Kruskal-Wallis test, Wilcoxon rank-sum test, and generalized estimating equations regression models. Both 1.0 and 0.21 groups were similar in systemic hemodynamics and cerebral blood flow, as well as survival (8/10). The 1.0 animals had relative cerebral hyperoxia during CPR and immediately following return of spontaneous circulation (brain tissue oxygen tension, 85% [interquartile range, 72%-120%] baseline in 0.21 animals versus 697% [interquartile range, 515%-721%] baseline in 1.0 animals; P=0.001 at 10 minutes postarrest). Cerebral mitochondrial reactive oxygen species production was higher in animals treated with 1.0 compared with 0.21 (P<0.03). Exposure to 1.0 oxygen led to increased cerebral oxidative injury to proteins and lipids, as evidenced by significantly higher protein carbonyls and 4-hydroxynoneals compared with 0.21 (P<0.05) and sham (P<0.001). Conclusions Exposure to 1.0 inspired oxygen during CPR caused cerebral hyperoxia during resuscitation, and resultant increased mitochondrial-derived reactive oxygen species and oxidative injury following cardiac arrest.
Keywords: brain; cardiac arrest; cardiopulmonary resuscitation; mitochondria; neuroprotection; oxygen.