Effect of dexmedetomidine on NF-kB activity during ventilator-induced lung injury in dogs

Abstract

Objective To evaluate the effect of dexmedetomidine on NF-κB activity in ventilator-induced lung injury in dogs.Methods Thirty healthy 5-year-old Beagles,weighing 10-12 kg,were randomly assigned into 5 groups (n =6 each) using a random number table:control group (group C),mechanical ventilation (MV) group and 3 different concentrations of dexmedetomidine groups (groups DEX1-3).The animals were anesthetized with pentobarbital sodium,ketamine and atropine.The rats were tracheostomized and spontaneous breathing was maintained in group C,while the rats were tracheostomized and mechanically ventilated for 4 h in MV and DEX1-3 groups.Tracheal intubation was performed in all the groups.The concentration of O2 inhaled was set at 50％,respiratory rate at 15 bpm,tidal volume at 20 ml/kg,and positive end-expiratory pressure at 2 cm H2 O.A loading dose of dexmedetomidine 0.5,1.0 and 2.0 μg/kg was infused over 20 min before intubation,followed by continuous infusion (lasting for4 h) at a rate of 0.5,1.0 and 2.0μg·kg-1 ·h-1 in DEX1-3 groups,respectively.Blood samples were taken from the femoral artery at baseline state,and 1,2 and 4 h of MV for detection of PaO2.The animals were sacrificed after 4 h of MV.The lungs were removed for determination of W/D lung weight ratio (W/ D ratio),myeloperoxidase (MPO) activity,NF-κB p65 expression (by Western blot) and TNF-α mRNA expression (by RT-PCR) in lung tissues.Results Compared with group C,W/D ratio,MPO activity,and expression of NFκB p65 and TNF-α mRNA were significantly increased in group MV (P ＜ 0.05).Compared with group MV,MPO activity,and expression of NF-κB p65 and TNF-α mRNA were significantly decreased,and no significant change was found in W/D ratio in DEX2 and DEX3 groups (P ＜ 0.05).Conclusion Dexmedetomidine can inhibit NF-κB activity and reduce inflammatory responses,thus improving ventilator-induced lung injury in dogs. Key words: Dexmedetomidine ; Respiration, artificial; Respiratory distress syndrome, adult; Inflammation