Effects of dexmedetomidine postconditioning on brain injury after cardiac arrest and resuscitation in a swine model

Objective To investigate the effects of dexmedetomidine postconditioning on brain injury after cardiac arrest and resuscitation in a swine model. Methods Twenty-eight healthy male domestic pigs, weighing 36±2 kg, were randomized (random number) into 4 groups (n=7 each group): sham operation group (S group), cardiopulmonary resuscitation group (CPR group), low-dose dexmedetomidine postconditioning group (LDP group), and high-dose dexmedetomidine postconditioning group (HDP group). Animals in the S group only underwent the surgical preparation. In the other three groups, the experimental model was established by 8 mins of electrically induced ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation. At 5 min after resuscitation, a loading dose of dexmedetomidine of 0.25 μg/kg was intravenously infused followed by continuous infusion at a rate of 0.25 μg/(kg·h) for 6 h in the LDP group, and a loading dose of dexmedetomidine of 0.5 μg/kg was infused followed by continuous infusion at a rate of 0.5 μg/(kg·h) for 6 h in the HDP group. The same amount of normal saline was administered in the S and CPR groups. At 1 h, 3 h, 6 h and 24 h after resuscitation, the levels of serum neuron specific enolase (NSE) and S100B protein were measured. At 24 h after resuscitation, neurologic deficit score (NSD) was evaluated. After that, the animals were euthanized and cerebral cortex was obtained for the determination of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity, cell apoptosis and caspase-3 expression. Results Compared with the S group, post-resuscitation neurologic dysfunction and brain injury were observed in the other three groups, which were indicated by significantly higher NDS and markedly greater levels of serum NSE and S100B (all P<0.05). Compared with the CPR group, the score of NDS at 24 h post-resuscitation were significantly lower and the levels of serum NSE and S100B at 6 h and 24 h post-resuscitation were significantly less in the LDP and HDP groups [NDS: 194±26, 103±16 vs 278±23 at 24 h; NSE (ng/mL): 32.4±1.8, 28.6±3.7 vs 36.2±2.8 at 6 h, 39.9±4.2, 35.1±1.5 vs 45.1±3.0 at 24 h;S100B (pg/mL): 2 534±207, 2 382±170 vs 2 825±113 at 6 h, 3 719±164, 3 246±176 vs 4 085±161 at 24 h, all P<0.05]. Compared with the LDP group, neurologic dysfunction and brain injury at 24 h post-resuscitation were further significantly alleviated in the HDP group (all P<0.05). Pathological analysis indicated that brain inflammation, oxidative stress and cell apoptosis were observed after resuscitation in the CPR, LDP and HDP groups. However, the contents of TNF-α, IL-6 and MDA were significantly lower while the activity of SOD was significantly higher, and cell apoptosis and caspase-3 expression were significantly reduced in the brain after resuscitation in the LDP and HDP groups compared with the CPR group (all P<0.05). In addition, those pathological injuries mentioned above were further significantly alleviated in the brain after resuscitation in the HDP group compared to the LDP group (all P<0.05). Conclusions Dexmedetomidine postconditioning significantly alleviated the severity of post-resuscitation brain injury in a dose-dependent manner, in which the protection was produced possibly through reducing tissue inflammation, oxidative stress and cell apoptosis. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Dexmedetomidine; Brain injury; Inflammatory response; Oxidative stress; Cell apoptosis; Swine