Therapeutic hypothermia effect on asphyxial cardiac arrest-induced renal ischemia/reperfusion injury via change of Nrf2/HO-1 levels

Exp Ther Med. 2021 Sep;22(3):1031. doi: 10.3892/etm.2021.10463. Epub 2021 Jul 18.

Abstract

The present study aimed to investigate the renoprotective effect of therapeutic hypothermia (TH) on renal ischemia-reperfusion injury (RI/RI) induced by asphyxial cardiac arrest (CA) in rats. A total of 48 male rats were randomly divided into five groups: i) Sham (n=6); ii) Normothermia + CA (Normo.) (n=14); iii) Normo. and 2 h of TH after return of spontaneous circulation (ROSC) (n=12); iv) Normo. and 4 h of TH after ROSC (n=9); and v) Normo. and 6 h of TH after ROSC (n=7). All rats except the Sham group underwent asphyxia CA and were sacrificed 1 day after ROSC. The survival rate increased from 42.8% in the Normo. group to 50, 66.6 and 85.7% in the groups with 2, 4 and 6 h of TH after CA, respectively. TH attenuated the histopathological changes of the renal tissues following ROSC and the levels of blood urea nitrogen, serum creatinine and malondialdehyde in renal tissues. On immunohistochemistry, the relative optical density of nuclear erythroid-related factor-2 (Nrf2) and heme oxygenase (HO-1) expression in renal tissues increased in the Normo. group compared with that in the Sham group and exhibited further significant increases at 6 h of TH after ROSC. In conclusion, TH attenuated renal injury and increased the expression of Nrf2 and HO-1 in a TH treatment time-dependent manner.

Keywords: cardiac arrest; cardiopulmonary resuscitation; heme oxygenase 1; nuclear erythroid-2-related factor 2; therapeutic hypothermia.

Grants and funding

Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (grant nos. NRF-2020R1I1A3070874, NRF-2019R1C1C1002564, NRF-2019R1F1A1062696 and 2019R1A6A1A03033084) and the Biomedical Research Institute of Jeonbuk National University Hospital.