Ameliorating effects of low tidal volume ventilation with associated hypercapnia on pneumoperitoneum-induced lung injury by inhibition of Toll-like receptor 4

Background: Mechanical ventilation using lower tidal volume ventilation with associated hypercapnia is supported to avoid ventilator-induced lung injury, but the underlying mechanism is not clear. This study was intended to explore whether low tidal volume ventilation with associated hypercapnia would ameliorate pneumoperitoneum-induced lung injury and whether this protection strategy might work through mediating inflammation and oxidative stress via TLR 4 signaling pathway. Materials and methods: 50 anesthetized Wistar Rats were randomized to be mechanically ventilated for 4 h at 7 groups: Group A, ventilated with 12 ml/kg; Group B, similar to Group A but injected with LPS (Toll receptor 4 agonist); Group C, similar to Group A but injected with Pam3Cys (Toll receptor 2 agonist); Group D, ventilated with 12 ml/kg and subjected to pneumoperitoneum; Group E, ventilated with 6 ml/kg and subjected to pneumoperitoneum; Group F, similar to Group E but injected with LPS; Group G, similar to Group E but injected with Pam3Cys. After animals were killed, indices of lung Injury, inflammation markers and oxidative stress markes of the lungs tissues, bronchoalveolar lavage fluid and blood were assessed. Results: The group subjected to pneumoperitoneum (Group D) had elevated values of indices of lung Injury, inflammation oxidative stress markers compared with the controls (Group A). The low tidal volume ventilation group (Group E) had significantly decreased values of markers of lung Injury, inflammation and oxidative stress compared with the high tidal volume ventilation group (Group D). LPS treatment reversed all the results of Group E, while Pam3Cys treatment had no significant effect. Conclusions: Low tidal volume ventilation with associated hypercapnia ameliorated pneumoperitoneum-induced lung injury by reducing TLR 4-mediated inflammation and oxidative stress.