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Background Pulmonary surfactant dysfunction may contribute to the development of ventilator induced lung injury (VILI). Tracheal gas insufflation (TGI) is a technique in which fresh gas is introduced into the trachea and augment ventilation by reducing the dead space of ventilatory system, reducing ventilatory pressures and tidal volume (VT) while maintaining constant partial arterial CO2 pressure (PaCO2). We hypothesised that TGI limited peak inspiratory pressure (PIP) and VT and would minimize conventional mechanical ventilation (CMV) induced pulmonary surfactant dysfunction and thereby attenuate VILI in rabbits with acute lung injury (ALI).Methods ALI was induced by intratracheal administration of lipopolysaccharide in anaesthetized, ventilated healthy adult rabbits randomly assigned to continuous TGI at 0.5 L/min (TGI group) or CMV group (n=8 for each group), and subsequently ventilated with limited PIP and VT to maintain PaCO2 within 35 to 45 mmHg for 4 hours. Physiological dead space to VT ratio (VD/VT), dynamic respiratory compliance (Cdyn) and partial arterial O2 pressure (PaO2) were monitored. After ventilation, lungs were analysed for total phospholipids (TPL), total proteins (TP), pulmonary surfactant small to large aggregates ratio (SA/LA) in bronchoalveolar lavage fluid (BALF) and for determination of alveolar volume density (Vv), myeloperoxidase and interleukin (IL)-8.Results TGI resulted in significant (P＜0.05 or P＜0.01) decrease in PIP [(22.4±1.8) cmH2O vs (29.5±1.1) cmH2O], VT [(6.9±1.3) ml/kg vs (9.8±1.11) ml/kg], VD/VT [(32±5)% vs (46±2)%], TP [(109±22) mg/kg vs (187±25) mg/kg], SA/LA (2.5±0.4 vs 5.4±0.7), myeloperoxidase [(6.2±0.5) U/g tissue vs (12.3±0.8) U/g tissue] and IL-8 [(987±106) ng/g tissue vs (24±3) mN/m] of BALF, and significant (P＜0.05) increase in Cdyn [(0.47±0.02) ml ·cmH2O-1 ·kg-1 vs (0.31±0.02) ml ·cmH2O-1 ·kg-1], PaO2 [(175±24) mmHg vs (135±26) mmHg],TPL/TP (52±8 vs 33±11) and Vv (0.65±0.05 vs 0.44±0.07) as compared with CMV.Conclusions In this animal model of ALI, TGI decreased ventilatory requirements (PIP, VT and VD/VT),resulted in more favourable alveolar pulmonary surfactant composition and function and less severity of lung injury than CMV. TGI in combination with pressure limited ventilation may be a lung protective strategy for ALI.