COMBINATION OF ANTIOXIDANTS AND TARGETED TEMPERATURE MANAGEMENT AMELIORATES POSTCARDIAC ARREST SYNDROME IN A RAT MODEL OF ASPHYXIAL CARDIAC ARREST

Background: Postcardiac arrest syndrome (PCAS) is a complex pathophysiological processes occurring after return of spontaneous circulation (ROSC) following cardiac arrest (CA), which may lead to multiple organ failure and death. The clinical efficacy of conventional therapies such as oxygen therapy and targeted temperature management (TTM) are remaining limited. Given the central role of oxidative stress in the progression of PCAS, we investigated the effect of combining antioxidants with TTM in an asphyxial CA rat model. Methods and Results: After 7 min of untreated asphyxial CA in Sprague-Dawley rats, animals were randomized into four groups: 1) placebo control (PBO); 2) trimetazidine (TMZ); 3) edaravone (EDA); 4) TMZ + EDA. Glucose (10 mL/kg), TMZ (10 mg/kg), saline (10 mL/kg), and EDA (3 mg/kg) were administered at 5 and/or 60 min after resuscitation. Animals were ventilated with 100% O 2 for 1 h after ROSC. Half of the animals were maintained at normothermia (37.5°C) and half at hypothermia (34.0°C). Under normothermia, the administration of EDA significantly improved 96-h survival rates, reduced the proportion of FJB-positive areas in the hippocampus and decreased malondialdehyde and 8-OHDG levels compared to normothermia PBO. Under hypothermia, the 96-h survival rates were markedly higher in TMZ, EDA, and TMZ + EDA groups than in hypothermia PBO. Furthermore, collagen volume fraction and the proportion of FJB-positive areas were markedly reduced, while malondialdehyde, 8-OHDG, and H 2 O 2 were significantly decreased in TMZ + EDA group. Conclusions : Combining antioxidants with TTM alleviates PCAS and improves outcomes by reducing reactive oxygen species levels and mitigating myocardial and cerebral pathological injury.