Effect of Therapeutic Hypothermia on Mitogen-activated Protein Kinase Pathways in the Brain Tissue of a Swine Cardiac Arrest Model

Kye, Yu Chan; Suh, Gil Joon; Kwon, Woon Yong; Kim, Kyung Su; You, Kyoung Min

J Korean Soc Emerg Med > Volume 27(5); 2016 > Article

Original Article

Journal of The Korean Society of Emergency Medicine 2016;27(5): 464-472.

Effect of Therapeutic Hypothermia on Mitogen-activated Protein Kinase Pathways in the Brain Tissue of a Swine Cardiac Arrest Model

Yu Chan Kye¹, Gil Joon Suh², Woon Yong Kwon², Kyung Su Kim², Kyoung Min You²

¹Department of Emergency Medicine, Veterans Health Service Medical Center, Seoul, Korea
²Seoul National University Hospital, Seoul, Korea

Correspondence

Gil Joon Suh ,Tel: 02-2072-2196, Fax: 02-3672-8871, Email: suhgil@snu.ac.kr,

Received: May 3, 2016; Revised: May 3, 2016 Accepted: August 17, 2016. Published online: October 30, 2016.

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.
Method:
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.