Protective effects of endothelin-1 recepter antagonist against lung injury during one-lung ventilation in rabbits

Abstract

Objective To investigate the protective effect of endothelin-1 (ET-1) recepter antagonist against lung injury during one-lung ventilation (OLV) in rabbits. Methods Fifteen big-ear Japanese rabbits (no limit of male or female) were divided into 3 groups randomly (n=5 in each group): sham group (group T), one-lung ventilation group (group O), OLV+ BQ-123 group (group OB). Two lungs were ventilated for 2.5 h in group T, and one lung was ventilated for 2.0 h followed by 0.5 h OLV in group O and group OB. About 10 min before one lung ventilation, BQ-123 (50 μg/kg) was injected through the femoral vein in group OB. Group O and group OB received the same amount of normal saline at the same time point. During the experiment, arterial blood gas analyses were done at the time of before OLV (T0), 1 h after OLV (T1), 2 h after OLV (T2) and 0.5 h after TLV (T3), as well as OI was calculated. At end of the experiment, the two lungs were removed for light microscopic evaluations, and the content of ET-1, activity of superoxide dismutase (SOD), concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined in lung tissures. Results As compared with group T, the content of ET-1 [(165.73±23.87) ng/L vs. (94.31±9.86) ng/L], the activity of SOD [(62.21±2.10) U/mg vs. (84.42±6.77) U/mg], the concentration of IL-6 [(20.82±1.33) ng/L vs. (7.97±1.98) ng/L] and TNF-α [(37.11±5.03) ng/L vs. (19.47±4.30) ng/L](P<0.05) in lung tissue of group O were increased, the pathological score was increased, and the OI was decreased at 2.0 hafter one-lung ventilation. As compared with group O, the content of ET-1 [(119.37±8.55) ng/L vs. (165.73±23.87) ng/L], the activity of SOD [(78.29±1.78) U/mg vs. (62.21±2.10) U/mg] and the concentrations of IL-6 [(14.13±1.26) ng/L vs. (20.82±1.33) ng/L] and TNF-α [(26.30±2.18) ng/L vs. (37.11±5.03) ng/L] in the collapsed lung tissue of group OB were decreased (P<0.05), and the pathological score decreased. In group O and OB, the content of ET-1 and concentrations of IL-6 and TNF-α in the collapsed lung were significantly higher than those in the ventilated lung, the activity of SOD was decreased and the pathological score was increased (P<0.05). Conclusion ET-1 receptor antagonist has protective effect on lung injury during one-lung ventilation in rabbits, which may be related to the reduction of ET-1 binding to receptor and the inhibition of inflammatory response and oxidative stress reaction in lung tissue. Key words: Lung injury; One-lung ventilation; Endothelin-1 recepter antagonist; Rabbit