Combinational therapy using hypothermia and FK506 to target oxidative stress, endothelial injury, inflammation, and ischemic brain injury after cardiac arrest in rat

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592738
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Yamaguchi University
• Principal Investigator: ODA Yasutaka 山口大学, 医学(系)研究科(研究院), 准教授 (40397998)
• Co-Investigator(Kenkyū-buntansha): FUJITA Motoki 山口大学, 医学(系)研究科(研究院), 助教 (50380001)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 心停止後症候群 / 心室細動 / 酸化ストレス / マロン酸アルデヒド / sICAM1 / HMGB1

Outline of Final Research Achievements

This study evaluated the utility of combinational therapy, coupling hypothermia with FK506 administration, on oxidative stress, endothelial injury, inflammation, and ischemic brain injury seen following cardiac arrest (CA). Rats were resuscitated from cardiac arrest by induced ventricular fibrillation, and subjected to various combinations of hypothermic/FK506 intervention. Cardiac arrest induced dramatic oxidative stress, endothelial injury, inflammation, and neuronal damages in hippocampus. Hypothermia or FK506 after CA provided limited protection. However, CA with combinational therapy achieved protection against oxidative stress, endothelial injury, inflammation, and ischemic brain injury. This study shows the benefits of combinational therapy, using hypothermia with FK506 to attenuate important features of CA. This suggests that hypothermia might protect and extend the therapeutic window for FK506 efficacy.

Free Research Field

救急医学