The benefits of respective and combined use of green tea polyphenols and ERK inhibitor on the survival and neurologic outcomes in cardiac arrest rats induced by ventricular fibrillation

Background: Cerebral injury is a main factor contributing to a high mortality after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Objective: We sought to evaluate the effect of green tea polyphenols (GTPs) and ERK1/2 inhibitor PD98059 (PD) on the survival and neurologic outcomes after CA/CPR in rats. Methods: First, rats were subjected to CA after CPR. The rats that restored spontaneous circulation were blindly allocated to the saline group (saline, IV, n = 12), the GTP group (GTPs, 10 mg/kg, IV, n = 12), the PD group (PD, 0.3 mg/kg, IV, n = 12), and the GTPs + PD group (GTPs, 10 mg/kg; PD, 0.3 mg/kg, IV, n = 12). Another 12 rats without experiencing CA and CPR were served as a sham group. Survival and the neurologic deficit score were observed for 72 hours after restoration of spontaneous circulation. Second, same experimental procedures were performed, and in 1 of 5 groups, animals were divided into 4 subgroups further according to the different time points (12, 24, 48, and 72 hours after restoration of spontaneous circulation [ROSC], n = 6/group). Brain tissues were harvested at relative time points for the morphologic evaluation as well as reactive oxygen species (ROS), malonylaldehyde, and superoxide dismutase (SOD) measurement. Results: Green tea polyphenols, PD, and a combination of GTPs and PD used after ROSC alleviated themorphologic changes of the cerebrum. These 3 treatments also decreased the productions of ROS and malonylaldehyde, increased SOD activities in cerebral tissues, and improved the neurologic deficit and survival rates at 12, 24, 48, and 72 hours after ROSC. Conclusions: Administration of GTPs and PD after ROSC can alleviate cerebral injury, improve the survival and neurologic outcomes via reduction of ROS, and increase of SOD activity in a rat CA/CPR model. (C) 2015 Elsevier Inc. All rights reserved.