Related Experiment Video
Updated: Jul 2, 2026
A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique
Published on: April 26, 2015
Sigma-1 receptor agonist SA4503 improves cerebral protective effects in an extracorporeal cardiopulmonary
Jie Yu1, Shuhong Chen2, Pingfei Xue3
1Department of Anaesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Objectives:
In this study, we applied a selective sigma-1 receptor agonist, SA4503, to an extracorporeal cardiopulmonary resuscitation rat model and investigated its cerebral protective effects and potential mechanisms.
Methods:
Eighteen male adult Sprague-Dawley rats were randomly allocated to 3 groups after anesthesia and identical preparation work, with 6 rats per group. The 2 intervention groups underwent asphyxiation-induced cardiac arrest and were rescued with and without SA4503. The SHAM group did not undergo cardiac arrest or rescue but received the same critical care as the intervention groups until the experiments ended. The end point was 1 hour after the return of spontaneous circulation or death. Hemodynamic and blood gas indicators were measured during surgery. Cerebral injury was evaluated histopathologically. Cerebrospinal fluid samples were collected by microdialysis. Rat hippocampal tissues from the intervention groups were used for whole-transcriptome sequencing.
Results:
Compared with extracorporeal cardiopulmonary resuscitation (ECPR) group, the ECPR + SA4503 group showed alleviated neuronal destruction of the CA1 region, which is illustrated by the pathologic pictures and the statistical result. In addition, the levels of excitatory amino acids of the ECPR + SA4503 group were lower than that of the ECPR group. In total, 74 differentially expressed genes were detected by RNA sequencing, most of which were related to inflammation, apoptosis, and oxidative stress. The phosphoinositide 3-kinase-AKT signaling pathway was selected by Kyoto Encyclopedia of Genes and Genomes pathway analysis, which may contribute to the cerebral protection of ECPR + SA4503, and was verified via western blotting. Finally, a lncRNA-miRNA-mRNA interactive ceRNA network was established to elucidate the mutual regulation among these three different kinds of RNAs.
Conclusions:
Our findings indicate that the sigma-1 receptor agonist SA4503 mitigates brain injury in an extracorporeal cardiopulmonary resuscitation rat model.
