Extracorporeal cardiopulmonary resuscitation with therapeutic hypothermia mitigates kidney injury following cardiac arrest in rats.

Many patients with cardiac arrest (CA) experience severe kidney injury following the return of spontaneous circulation (ROSC). This study aimed to compare the renal protective effect of conventional cardiopulmonary resuscitation (CCPR), extracorporeal cardiopulmonary resuscitation (ECPR), and ECPR with therapeutic hypothermia (ECPR+T) in a CA rat model. Twenty-four adult male Sprague-Dawley rats were randomly and equally allocated into the SHAM, CCPR, ECPR, and ECPR+T groups. The SHAM group underwent basic surgical procedures without asphyxia-induced CA. The other three groups were treated with asphyxiation to establish the CA model. Subsequently, they were rescued using three different therapeutic methods. The endpoints were 1 h after ROSC or death. Renal injury was evaluated by histopathology. Oxidative stress, endoplasmic reticulum stress, necroptosis, inflammatory, and apoptosis-related genes, and proteins were detected using western blotting, ELISA, and assay kit. Compared with CCPR, ECPR and ECPR+T alleviated oxidative stress by upregulating nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione and downregulating heme oxygenase-1, and malondialdehyde. Expression of endoplasmic reticulum stress-related proteins, glucose-regulated protein 78, and CCAAT/enhancer-binding protein homologous protein was lower in ECPR and ECPR+T groups than that in the CCPR group, along with levels of tumor necrosis factor-alpha, interleukin 6, and interleukin 1-beta, and necroptosis proteins (receptor-interacting serine/threonine kinase [RIP]1 and RIP3). Further, the ECPR and ECPR+T groups had significantly increased B-cell lymphoma 2 (bcl-2) and decreased bcl-2-associated X levels compared with the CCPR group. ECPR and ECPR+T alleviate kidney damage following CA in rats compared with CCPR. Furthermore, ECPR+T had a better renal protective effect.