Exogenous surfactant reduces ventilator-induced decompartmentalization of tumor necrosis factor alpha in absence of positive end-expiratory pressure.

Abstract

To determine the effect of pretreatment with exogenous surfactant on ventilator-induced decompartmentalization of TNF-alpha. Prospective, randomized, animal study in the experimental laboratory of a university. Male Sprague-Dawley rats (n=102) received lipopolysaccharide either intratracheally or intraperitoneally to stimulate TNF-alpha production; one-half of the animals were pretreated with surfactant. Animals were ventilated for 20 min with a peak inspiratory pressure/positive end-expiratory pressure (PEEP) ratio of either 45/0 or 45/10 (frequency 30 bpm, I/E ratio 1:2, FIO(2)=1). Blood gas tension and arterial pressures were recorded 1, 10, and 20 min after the start of mechanical ventilation. After the animals were killed pressure-volume curves were recorded, and bronchoalveolar lavage was performed for assessment of protein content and the small/large surfactant aggregate ratio. TNF-alpha was determined in serum and bronchoalveolar lavage. Pretreatment with surfactant decreased decompartmentalization of TNF-alpha during 45/0 ventilation. Addition of a PEEP level of 10 cm H(2)O reduced decompartmentalization even further. In addition, surfactant prevented deterioration in oxygenation and decreased accumulation of protein in the bronchoalveolar lavage in the zero-PEEP group. An excess of active surfactant decreases transfer of cytokines across the alveolar-capillary membrane similar to PEEP. The combination of PEEP and surfactant reduces decompartmentalization of TNF-alpha even further.