Ventilation with high tidal volume induces inflammatory lung injury

Abstract

Mechanical ventilation with high tidal volumes (VT) has been shown to induce lung injury. We examined the hypothesis that this procedure induces lung injury with inflammatory features. Anesthetized male Wistar rats were randomized into three groups: group 1 (N = 12): VT = 7 ml/kg, respiratory rate (RR) = 50 breaths/min; group 2 (N = 10): VT = 21 ml/kg, RR = 16 breaths/min; group 3 (N = 11): VT = 42 ml/kg, RR = 8 breaths/min. The animals were ventilated with fraction of inspired oxygen of 1 and positive end-expiratory pressure of 2 cmH2O. After 4 h of ventilation, group 3, compared to groups 1 and 2, had lower PaO2 [280 (range 73-458) vs 517 (range 307-596), and 547 mmHg (range 330-662), respectively, P<0.05], higher wet lung weight [3.62±0.91 vs 1.69±0.48 and 1.44±0.20 g, respectively, P<0.05], and higher wet lung weight/dry lung weight ratio [18.14 (range 11.55-26.31) vs 7.80 (range 4.79-12.18), and 6.34 (range 5.92-7.04), respectively, P<0.05]. Total cell and neutrophil counts were higher in group 3 compared to groups 1 and 2 (P<0.05), as were baseline TNF-α concentrations [134 (range <10-386) vs 16 (range <10-24), and 17 pg/ml (range <10-23), respectively, P<0.05]. Serum TNF-α concentrations reached a higher level in group 3, but without statistical significance. These results suggest that mechanical ventilation with high VT induces lung injury with inflammatory characteristics. This ventilatory strategy can affect the release of TNF-α in the lungs and can reach the systemic circulation, a finding that may have relevance for the development of a systemic inflammatory response.