Prostaglandin E1 Attenuates Post-Cardiac Arrest Myocardial Dysfunction via Inhibiting Mitochondria-Mediated Cardiomyocyte Apoptosis

Background: Post-cardiac arrest myocardial dysfunction (PAMD) is a leading cause of death in resuscitated patients after cardiac arrest (CA). Prostaglandin E1 (PGE1) is a clinical drug used to mitigate ischemia injury. However, its effect on PAMD remains unknown. Methods: We investigated the protective effects of PGE1 on PAMD in a rat model of cardiac arrest and a hypoxia-reoxygenation (H/R) H9c2 cell model. Forty-two male Wistar rats were randomly assigned to CA, CA+PGE1, and sham groups. Asphyxia for 8 min followed by cardiopulmonary resuscitation was performed in the CA and CA+PGE1 groups. PGE1 (1 μg/kg) was intravenously administered at the onset of return of spontaneous circulation (ROSC). Ejection fraction (EF) and cardiac output (CO) were measured at baseline, 1, 2, 3, and 4 h after ROSC; survival was monitored for 72 h. Cardiomyocyte apoptosis, mitochondrial permeability transition pore (mPTP) opening, and protein levels of glycogen synthase kinase 3β (GSK3β), cytochrome c, and cleaved caspase-3 were measured 4 h after ROSC. H9c2 cells were treated with PGE1(0.5 μM) at the start of reoxygenation. Apoptosis, mPTP opening, and protein levels of GSK3β, cytochrome c, and cleaved caspase-3 of H9c2 cells were detected. Results: Compared to the CA group, PGE1 treatment significantly increased the EF and CO within 4 h after ROSC and improved the survival rate. It activated GSK3β, prevented mPTP opening, suppressed cytochrome c and cleaved caspase-3 expression, and reduced cardiomyocyte apoptosis in the rat model. In vitro, Changes in GSK3β, mPTP opening, cytochrome c and cleaved caspase-3 expression, and apoptosis in H9c2 cells were consistent with those in the rat model. Conclusions: Our results indicate that PGE1 attenuates PAMD via inhibiting mitochondria-mediated cardiomyocyte apoptosis.