Olanzapine-Induced Therapeutic Hypothermia Attenuates Renal Injury in Rats after Asphyxial Cardiac Arrest and Resuscitation

Abstract

Return of spontaneous circulation (ROSC) through cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) causes post-cardiac arrest syndrome (PCAS) due to dysfunction in various organs, which provokes acute kidney injury because of renal ischemia-reperfusion injury. Therapeutic hypothermia (TH) can reduce PCAS after CA and ROSC. However, it needs to be more sophisticated and effective. Hence, we aimed to elucidate the protective effects of olanzapine-induced TH against renal injury in asphyxial CA-induced rats. Every rat’s body temperature was maintained at 33 °C for 6 h after administering olanzapine post-CA and ROSC. Olanzapine-induced TH dramatically increased the survival rate of the rats and ameliorated renal tissue damage. Moreover, it suppressed oxidative stress responses through preservation of mitochondrial function and endoplasmic reticulum stress as the main contributor of oxidative stress. Notably, these actions of olanzapine-induced TH were mediated through the Sirt3-related signaling pathway, including the maintenance of Sirt3 and FOXO3a protein expression and the activation of AMPKα and superoxide dismutase 1 (SOD2, a mitochondrial antioxidant). This study is the first to disclose the protective effects of olanzapine-induced TH against renal injury after CA and ROSC, suggesting that olanzapine-induced TH could be utilized for treating CA followed by ROSC.

Keywords

• cardiac arrest
• ROSC
• ischemia–reperfusion injury
• oxidative stress
• reactive oxygen species
• Sirt3