EXTRACORPOREAL CARDIOPULMONARY RESUSCITATION WITH THERAPEUTIC HYPOTHERMIA MITIGATES KIDNEY INJURY AFTER CARDIAC ARREST IN RATS.

Abstract

Many patients with cardiac arrest (CA) experience severe kidney injury after the return of spontaneous circulation. 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 end points were 1 h after return of spontaneous circulation 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 TNF-α, IL-6, and IL-β, and necroptosis proteins (receptor-interacting serine/threonine kinases 1 and 3). Furthermore, the ECPR and ECPR+T groups had significantly increased B-cell lymphoma 2 and decreased B-cell lymphoma 2-associated X levels compared with the CCPR group. Extracorporeal cardiopulmonary resuscitation and ECPR+T alleviate kidney damage after CA in rats compared with CCPR. Furthermore, ECPR+T had a better renal protective effect.