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Background Oxygen plays a pivotal role in cardiopulmonary resuscitation (CPR) and postresuscitation intervention for cardiac arrest. However, the optimal method to reoxygenate patients has not been determined. This study investigated the effect of timing of hyperoxygenation on neurological outcomes in cardiac arrest/CPR rats treated with targeted temperature management. Methods and Results After induction of ventricular fibrillation, male Sprague‐Dawley rats were randomized into 4 groups (n=16/group): (1) normoxic control; (2) O2 _CPR, ventilated with 100% O2 during CPR; (3) O2 _CPR+postresuscitation, ventilated with 100% O2 during CPR and the first 3 hours of postresuscitation; and (4) O2 _postresuscitation, ventilated with 100% O2 during the first 3 hours of postresuscitation. Targeted temperature management was induced immediately after resuscitation and maintained for 3 hours in all animals. Postresuscitation hemodynamics, neurological recovery, and pathological analysis were assessed. Brain tissues of additional rats undergoing the same experimental procedure were harvested for ELISA‐based quantification assays of oxidative stress–related biomarkers and compared with the sham‐operated rats (n=6/group). We found that postresuscitation mean arterial pressure and quantitative electroencephalogram activity were significantly increased, whereas astroglial protein S100B, degenerated neurons, oxidative stress–related biomarkers, and neurologic deficit scores were significantly reduced in the O2 _CPR+postresuscitation group compared with the normoxic control group. In addition, 96‐hour survival rates were significantly improved in all of the hyperoxygenation groups.Conclusions In this cardiac arrest/CPR rat model, hyperoxygenation coupled with targeted temperature management attenuates ischemia/reperfusion‐induced injuries and improves survival rates. The beneficial effects of high‐concentration oxygen are timing and duration dependent. Hyperoxygenation commenced with CPR, which improves outcomes when administered during hypothermia.

Hyperoxygenation With Cardiopulmonary Resuscitation and Targeted Temperature Management Improves Post–Cardiac Arrest Outcomes in Rats