title: Ventilator-induced lung injury leads to loss of alveolar and systemic compartmentalization of tumor necrosis factor-alpha.
abstract: OBJECTIVE
  To determine the effect on compartmentalization of the tumor necrosis factor (TNF)-alpha response in the lung and systemically after ventilation with high peak inspiratory pressure with and without positive end-expiratory pressure (PEEP).
  
  
  METHODS
  Prospective, randomized, animal study in an experimental laboratory of a university.
  
  
  METHODS
  85 male Sprague-Dawley rats. Lipopolysaccharide was given intratracheally or intraperitoneally to stimulate TNF-alpha 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).
  
  
  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-alpha was determined in serum and BAL. TNF-alpha levels were significantly increased after lipopolysaccharide stimulation; furthermore ventilation without PEEP resulted in a significant shift of TNF-alpha 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.
authors: Department of Anesthesiology, Erasmus University Rotterdam, The Netherlands.
authors: J J
authors: JJ
authors: Haitsma
authors: S
authors: S
authors: Uhlig
authors: R
authors: R
authors: Göggel
authors: S J
authors: SJ
authors: Verbrugge
authors: U
authors: U
authors: Lachmann
authors: B
authors: B
authors: Lachmann
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D007249:Inflammation; D008070:Lipopolysaccharides; D008297:Male; D011175:Positive-Pressure Respiration / Q000009:adverse effects* / Q000379:methods; D011446:Prospective Studies; D011650:Pulmonary Alveoli / Q000737:chemistry*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D013990:Tidal Volume; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha