Low tidal volume ventilation alleviates ventilator-induced lung injury by regulating the NLRP3 inflammasome.

PURPOSE:Low tidal volume ventilation (LTVV) is a well-known ventilation mode which can improve ventilator-induced lung injury (VILI). However, the mechanism of LTVV ameliorating VILI has not yet been elucidated. In this study, we aimed to reveal LTVV protected against VILI by inhibiting the activation of the NLRP3 inflammasome in bronchoalveolar lavage fluid (BALF) from humans and lungs from mice. MATERIALS AND METHODS:Twenty-eight patients scheduled for video-assisted thoracoscopic esophagectomy were randomized to receive high-tidal-volume ventilation [Vt = 10 mL/kg without positive end-expiratory pressure (PEEP)] or LTVV (Vt = 5 mL/kg along with 5 cm of H2O PEEP) during one-lung ventilation. BALF was collected before and at the end of surgery. Male C57BL/6 mice received high-tidal-volume ventilation, LTVV or MCC950 (an inhibitor of NLRP3). The activation of the formation of NLRP3 inflammasome in BALF from patients and in lungs from mice were analyzed. RESULTS:LTTV decreased the peak airway pressure (Ppeak), plateau airway pressure (Pplat) and driving pressure (ΔP) during one-lung ventilation. Additionally, LTVV not only inhibited pulmonary infiltration and inflammation caused by mechanical ventilation, but also suppressed the NLRP3 inflammasome activation in BALF from humans. In mice, ventilator-induced inflammatory response and pulmonary edema were suppressed by LTVV with an efficacy comparable to that of MCC950 treatment. Furthermore, LTVV, similar to MCC950, clearly decreased ventilator-induced NLRP3 inflammasome activation. CONCLUSION:Our study showed that LTVV played a protective role in ventilator-induced lung injury by suppressing the activation of the NLRP3 inflammasome. TRIAL REGISTRATION:This study was registered in The Chinese Clinical Trial Registry, ChiCTR1900026190 on 25 September 2019.