Abstract 126: The Effect of H2O2-Activatable Antioxidant Nanoparticles on Whole Body Ischemia/Reperfusion Injury in Rats
Cardiac resuscitation after cardiac arrest is a serious medical dilemma resulting in multiple organ injuries even after successful resuscitation mainly due to ischemia/reperfusion (I/R) injuries. Recently, we generated H2O2-activatable antioxidant nanoparticles formulated from copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a whole body ischemia/reperfusion (WBIR) injury model in rat. Animals were gender and age matched, and there was no statistical difference in baseline mean blood pressure (BP) in vehicle and PVAX-treated groups. To induce cardiac arrest, 70μl/100g body weight (BW) of cold 1M KCl was administered via the jugular venous catheter. Cardiac arrest was confirmed by drop of arterial blood pressure via continuous invasive monitoring. All rats underwent cardiac arrest for 5.5 mins. During cardiac arrest, the endotracheal tube was disconnected from the ventilator and isoflurane administration was turned off. After cardiac arrest, the ventilator was turned on and the endotracheal tube was reconnected. For resuscitation, 20μg/100g BW of epinephrine was injected i.v. and chest compressions were performed at a rate of 300 compressions/min. We found that mean time to the restoration of spontaneous circulation was reduced by 2-fold in PVAX treated group compared to the vehicle after WBIR (66.8±15.2 vs 127.3±83.2 sec). We also found that PVAX effectively blocked reactive oxygen species (ROS) generation in multiple organs as determined by dihydroethidium staining as an indicator of ROS generation after IR. Evaluation of pro-inflammatory cytokines, such as TNF-α and MCP-1 were significantly increased in heart, brain and kidney after 24 hr post-WBIR. PVAX treated group showed significantly reduced expression of pro-inflammatory cytokines after WBIR after PVAX treatment, particularly evident in heart. In addition, WBIR+vehicle group showed significant increase in apoptosis, as determined by TUNEL staining, but PVAX treated group effectively reduced apoptosis in multiple organs. Thus, we concluded that PVAX could be an effective therapeutic agent for treating WBIR injury via its blocking ROS-mediated damage.
Author Disclosures: S. Rhee: None. S. Bae: None. T. Kang: None. Q. Ke: None. J. Yoon: None. P.M. Kang: None.
- © 2014 by American Heart Association, Inc.