Abstract 20835: Flavonoids Baicalein Improves Post-resuscitation Survival and Neurological Prognoses not only by Antioxidant Protection but by Akt-eNOS-mediated Augmentation of Cerebral Perfusion
Background: Neurological injury is common after cardiopulmonary resuscitation (CPR), and is in part due to compromise of brain blood flow in the post-resuscitation phase. As a result of global ischemia and reperfusion (I-R), such injury is also caused by oxidative stress resulting from I-R. Flavonoids baicalein, being an oxidant scavenger, has been shown excellent antioxidant protection against I-R injury. It has also been reported to induce endothelium-dependent vasodilatation. We therefore sough to explore the potentials of baicalein in enhancing brain perfusion and mitigating oxidative injury in the post-resuscitation phase.
Methods: Using an established rat model of asphyxia cardiac arrest and CPR, we administered baicalein (20 mg/kg) 2 h before cardiac arrest and compared with standard CPR control. The systemic blood was sampled for measuring the reactive oxygen species (ROS) using chemiluminescence method. The cerebral perfusion was continuously recorded by OxyFLO detector. Two hours after return of spontaneous circulation (ROSC), the brain was harvested for measuring the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In a subgroup, the survival and neurological outcomes were monitored up to 3 days.
Results: In standard CPR group, the cerebral perfusion was compromised while ROS generation was increased after CPR. In baicalein group, the ROS generation was reduced compared to control (P < 0.05). Meanwhile, the cerebral perfusion post-ROSC was augmented (P < 0.05). In contrast, if the animals were treated with ascorbic acid, the ROS generation was reduced but the brain blood flow was not affected. The survival and neurological outcomes in baicalein group were better on day 3 (Logrank P < 0.001 and P < 0.01, respectively). The phosphorylated Akt and eNOS 2 h post-ROSC were significantly higher in the baicalein group (both P < 0.05). If NOS inhibitor N ω -nitro-L-arginine methyl ester (10 mg/kg) was cotreated with baicalein, the enhanced cerebral blood flow was reversed and protection partially abrogated.
Conclusions: Baicalein improves post-resuscitation survival and neurological outcomes not only by antioxidant protection but by enhancement of cerebral perfusion. Such protection is in part mediated by Akt-eNOS pathway.
- Cerebrovascular circulation
- Oxidative stress
- Cardiopulmonary resuscitation
- Cardiac arrest
- Nitric oxide synthase
- © 2010 by American Heart Association, Inc.