Abstract 277: Long-Term Daily Prophylactic Supplement With Melatonin as a Health Care Medicine Significantly Improved Survival and Neurological Outcome After Cardiac Arrest

Abstract

Introduction: Prophylactic pharmacotherapy for health care in reducing death after cardiac arrest (CA) is an elusive and less explored strategy. Melatonin, a natural health product contributing to sleep, was elevated upon arousal from torpor in hibernating mammals, which increased survival after blood return and reduced reperfusion injury. In this study, we sought to find the effects of long-term daily prophylactic supplement with melatonin as a health care medicine on the victim of CA. Methods: SD rats, 240-340 g, were used in this study. Sham, CA, and melatonin + CA (Mel + CA) groups were included. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 mins asphyxia and followed by manual CPR. The endpoint was 24 h after resuscitation. Neurological outcome was assessed. Hippocampal mitochondrial integrity, dynamics and function were observed. Results: Survival in the Mel + CA group was significantly higher than in the CA group (78% vs. 44%, P = 0.036). NDS was better in the Mel + CA group than the CA group ( P < 0.001). Neurons of CA1 were less damaged in the Mel + CA group than in the CA group (Figure). The mitochondria integrity in the CA group was severely damaged compared with the Mel + CA group. Sirt3 was highly expressed in the Mel + CA group than in the CA group ( P < 0.05). Ac-CypD was lower in the Mel + CA group than in the CA group ( P < 0.05). Drp1 was lower in the Mel + CA group than in the CA group ( P < 0.05). LC3 was highly expressed in the Mel + CA group than in the CA group ( P < 0.05). ΔΨm, mitochondria respiratory rate, and respiratory control rate were higher in the Mel + CA group than in the CA group ( P < 0.05). ROS production was lower in the Mel + CA group ( P < 0.05). Cleaved caspase-3 and caspase-9 were lower in the Mel + CA group ( P < 0.05). Conclusions: Long-term daily prophylactic supplement with melatonin as a health care medicine significantly improved survival, neurological outcome and neuronal mitochondrial function after cardiac arrest.