Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-α

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Abstract
Objectives: To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-α response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP). Design and setting: Prospective, randomized, animal study in an experimental laboratory of a university. Subjects and interventions: 85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-α production; control animals received a similar amount of saline. Animals were subsequently ventilated for 20 min in a pressure control mode with peak inspiratory pressure/PEEP ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO2=1). Measurements and results: Blood gas tension and arterial pressures were recorded at 1, 10, and 20 min after start of mechanical ventilation. After killing of the animals pressure-volume curves were recorded, and bronchoalveolar lavage (BAL) was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-α was determined in serum and BAL. TNF-α levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-α to the nonstimulated compartment as opposed to ventilation with a PEEP level of 10 cmH2O. Conclusions: Ventilation strategies which are known to induce ventilation-induced lung injury (VILI) disturb the compartmentalization of the early cytokines response in the lung and systemically. Furthermore, the loss of compartmentalization is a two-way disturbance, with cytokines shifting from the vascular side to the alveolar side and vice versa. A ventilation strategy (PEEP level of 10 cmH2O) which prevents VILI significantly diminished this shift in cytokines.

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