Abstract 15419: Protective Effects of Hoe-642 on the Neuronal Mitochondria in Asphyxial Cardiac Arrest Model in Rats
Introduction: The opening of mitochondrial permeability transition pore (mPTP) was an important event during ischemia/reperfusion injury. HOE-642, an inhibitor of Na+/H+ exchanger 1, delays the opening of mPTP and produces protective effects after traumatic brain injury. Few studies demonstrated the neuroprotective effects of HOE-642 after cardiac arrest.
Hypothesis: HOE-642 protects neuronal mitochondrial function after cardiac arrest.
Methods: Cardiac arrest was induced by 8 min asphyxia. Rats were divided into 3 groups (n=5 each): sham, (S group); normothermia group (N group), rectal temperature maintained at 37±0.5°C during cardiac arrest, CPR, and post-ROSC ventilating period of 1 h; HOE-642 group (H group), a bolus of HOE-642 (1 mg/kg) given when initiating CPR. After 24 h of resuscitation, the hippocampal mitochondria of rats were isolated. The mitochondrial membrane potential was expressed by intensity ratio of aggregation and monomer of fluorescent probe JC-1. Mitochondrial swelling was triggered by the addition of CaCl2 and monitored by an absorbance microplate reader at 520 nm. ROS production was detected.
Results: The baseline characters were not different between groups. The fluorescence intensity ratio of aggregation and monomer of JC-1 in the H group (3.80±0.75) was significantly higher than in the N group (1.74±0.83, P<0.05). The fluorescence intensity ratio of aggregation and monomer of JC-1 in the S group (2.55±0.91) was not different compared with the N group and the H group. The absorbance decrease in the N group was faster than in the S group and the H group (P<0.05, Figure). There was no difference in absorbance decrease between the S group and the H group. There was no difference in the production of ROS between groups.
Conclusions: HOE-642 used when initiating CPR inhibited mitochondrial membrane depolarization and prevented mitochondrial swelling. HOE-642 protected neuronal mitochondrial function after cardiac arrest.
Author Disclosures: P. Zhang: None. J. Dong: None. C. Nie: None. X. Liu: None. L. Wei: None. F. Han: None.
- © 2016 by American Heart Association, Inc.