J Korean Soc Emerg Med.
2016 Oct;27(5):464-472. 10.0000/jksem.2016.27.5.464.
Effect of Therapeutic Hypothermia on Mitogen-activated Protein Kinase Pathways in the Brain Tissue of a Swine Cardiac Arrest Model
- Affiliations
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- 1Department of Emergency Medicine, Veterans Health Service Medical Center, Seoul, Korea.
- 2Department of Emergency Medicine, Seoul National University Hospital, Seoul, Korea. suhgil@snu.ac.kr
- KMID: 2358288
- DOI: http://doi.org/10.0000/jksem.2016.27.5.464
Abstract
- PURPOSE
To investigate the change in mitogen-activated protein kinase pathways in the brain tissue after therapeutic hypothermia in the swine cardiac arrest model.
METHODS
After the return of spontaneous circulation by cardiopulmonary resuscitation, following a 6 min of no-flow time induced by ventricular fibrillation, pigs (n=24) were randomly assigned to one of four groups (sham, normothermia, 24 hr of therapeutic hypothermia, 48 hr of therapeutic hypothermia). After 24 or 48 hr of therapeutic hypothermia (core temperature 32-34℃), the pigs were then rewarmed to 36℃ for a period of 8 hr. At 60 hr upon the return of spontaneous circulation, the pigs were sacrificed and brain tissues were harvested.
RESULTS
We measured the tissue levels of p38, JNK, and ERK pathway expressions from the hippocampus of the swine brain in all four groups. The phosphorylated p38-to-p38 ratio and phosphorylated JNK-to-JNK ratio were significantly increased in all of the intervention groups compared with the sham group. The phosphorylated ERK-to-ERK ratio was increased only in the therapeutic hypothermia groups (p-value=0.026 in the 24 hr of therapeutic hypothermia group and p-value=0.002 in the 48 hr of therapeutic hypothermia group, compared with the sham group).
CONCLUSION
The p38 and JNK pathways were also activated during therapeutic hypothermia and normothermia. However, the ERK pathway was activated only in therapeutic hypothermia. Therapeutic hypothermia activated the ERK pathway in ischemia-reperfusion injury of the brain tissue after cardiac arrest, which seemed to be dependent on the duration of therapeutic hypothermia.
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