Abstract 14296: Hyperoxic Reperfusion in the Post-Resuscitation Phase Compromises Cerebral Perfusion and Increases Oxidative Neuronal Injury
Background: Hyperoxia after cardiopulmonary resuscitation (CPR) has been shown to adversely affect post-resuscitation survival and neurological prognoses. The pathogenic mechanisms, however, remain largely unknown. We therefore sough to investigate the effects of hyperoxic reperfusion on post-resuscitation oxidative injury, cerebral tissue perfusion, and the underlying mechanisms.
Methods: Using an established rat model of asphyxia cardiac arrest and CPR, we employed hyperoxic (100% O2) ventilation in the first 2 h after return of spontaneous circulation (ROSC), and compared cerebral tissue perfusion and oxygenation with those of normoxia (21% O2) control. The blood pressure was continuously monitored. Arterial blood was serially sampled for gas analysis and ROS measurement using chemiluminescence method. Cerebral tissue perfusion and oxygenation were assessed by OxyFLO/OxyLyte sensors. Real-time cerebral oxidative stress was detected by in vivo luminol chemiluminescence emission. Brain was harvested 2 h after ROSC for measurement of malondialdehyde (MDA), phosphorylated Akt (p-Akt) and eNOS (p-eNOS). In a subgroup with minimal invasive procedure, survival and neurological outcomes were monitored up to 3 days.
Results: Compared to normoxia CPR control, the PaO2 and cerebral tissue oxygenation in hyperoxia group were significantly higher in the first 2 h post-resuscitation (both P < 0.001). Cerebral tissue perfusion, however, fell rapidly to less than half that of per-arrest level after CPR. In contrast, the cerebral perfusion in normoxia group was relatively preserved and significantly higher than that of hyperoxia group (P < 0.01). For oxidative stress, real-time blood and brain ROS were significantly higher in hyperoxia group. Brain tissue MDA was also higher. In terms of hyperoxia-related hypoperfusion, both p-Akt and p-eNOS were significantly lower in hyperoxia group. The survival and neurological outcomes were both significantly better in normoxia group.
Conclusion: Hyperoxia in the post-resuscitation phase compromises cerebral perfusion and worsens oxidative injuries compared to normoxia control. The p-Akt and p-eNOS were significantly lower, which in part lead to compromised blood flow as a result of vasoconstriction.
- © 2012 by American Heart Association, Inc.