The effects of resolvin D1 on brain injury after cardiopulmonary resuscitation in swine and its potential mechanisms

Abstract

Objective To explore the role of resolvin D1 in reducing brain injury after porcine cardiopulmonary resuscitation and its potential mechanisms. Methods Twenty-eight male domestic pigs weighing (36±3)kg were utilized. The animals were randomly divided into 4 groups (n=7 each): sham operation group (group S), cardiopulmonary resuscitation group (group CPR), low-dose resolvin D1 group (group LRD), and high-dose resolvin D1 group (group HRD). The animals in group S only got the general preparation without the procedure of cardiac arrest and resuscitation. The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation. At 5 min post-resuscitation, the doses of resolvin D1 0.3 μg/kg, and 0.6 μg/kg were correspondingly injected via the femoral vein in LRD and HRD groups, and meanwhile the same amount of vehicle was given into the animals in the other two groups. At 3 h, 6 h and 24 h post-resuscitation, the concentrations of neuron specific enolase (NSE) and S100B protein (S100B) in serum was measured. At 24 h post-resuscitation, neurological deficit score (NDS) was evaluated; thereafter the pigs were sacrificed, and cerebral cortex was obtained for the determination of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) contents, and superoxide dismutase (SOD) activity. Results Compared to group S, post-resusci-tation brain injury was observed in the other three groups, which was indicated by significantly increased NDS score, and markedly elevated concentrations of serum NSE and S100B. Compared to group CPR, the NDS was significantly decreased at 24 h post-resuscitation, and the concentrations of serum NSE and S100B were significantly reduced at 6 h and 24 h post-resuscitation in LRD and HRD groups. Compared to group LRD, the NDS score and its serum markers were further significantly decreased in group HRD. The inflammatory response and oxidative stress in brain tissue were observed in all the animals experiencing cardiac arrest and resuscitation, which were indicated by increased contents of TNF-α, IL-6 and MDA and decreased SOD activity. Compared to group CPR, the contents of TNF-α, IL-6 and MDA were significantly decreased while SOD activity was significantly increased in LRD and HRD groups. The indicators of inflammatory response and oxidative stress in brain tissue were further significantly improved in group HRD when compared to group LRD. Conclusions Resolvin D1 can reduce post-resuscitation brain injury in a dose-dependent manner in swine, and the mechanism is related to the inhibition of inflammatory response and oxidative stress. Key words: Fatty acids, unsaturated; Cardiopulmonary resuscitation/AE; Brain injuries/ET; Swine