The effect of win55, 212-2 on neuronal apoptosis in post-resuscitation in rats

Objective To investigate the pharmacological hypothermic effect of WIN55, 212-2 on neuronal apoptosis after cardiopulmonary resuscitation. Methods Cardiac Arrest (CA) was induced in Sprague-Dawley rats. Five minutes after onset of CA, cardiopulmonary resuscitation (CPR) was carried out. At 30 minutes post-resuscitation, the animals were randomized into three groups (n=10 in each group): (1) WIN55, 212-2 hypothermia group [W group, WIN55, 212-2, 1 mg/(kg·h)]. (2) Normothermia group (NT group, 5% DMSO); (3) WIN55, 212-2 with normothermia group (W+ NT group, WIN55, 212-2, 1 mg/(kg·h). Animals in WIN55, 212-2 hypothermia group and WIN55, 212-2 with normothermia group were dealt with continuous intravenous infusion of WIN55, 212-2[1 mg/(kg·h)] for 4 h, while rats in NT group were infused with equal volume of 5% DMSO instead. The survival time and neurological deficit score (NDS) were observed. The CA models were established in three groups. After rats were sacrificed, the brains were harvested for detecting histopathological changes and apoptosis of neural cell at 24 h, 48 h and 72 h after ROSC respectively. Five animals of each group were chosen randomly(random number). Results Body temperatures of rats in W group decreased from 37°C to 34°C in 4 hours. Accumulated survival rate in W group was higher than that in the other two groups (P=0.02). NDS was significantly improved in W group than that in the other two groups (P<0.05). Morphological change in W group was less serious than that in the other two groups. The number of neuron apoptosis in W group was smaller than that in the other two groups. Conclusions WIN55, 212-2 inducing pharmacologically hypothermia during post-resuscitation prolonged survival and improved cerebral function in rat cardiac arrest models. The beneficial effects of WIN55, 212-2 were associated with ameliorating the histopathological damage in brain and alleviating the neuron apoptosis. Key words: Cardiopulmonary resuscitation; WIN55, 212-2; Pharmacological hypothermia; Apoptosis