Effects of low lung volume ventilation on respiratory mechanics and nitric oxide exhalation in normal rabbits

Exhaled NO (NOe), tumor necrosis factor α (TNF) in serum and bronchoalveolar lavage fluid (BALF), and lung mechanics were assessed in 8 closed and 8 open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with fixed tidal volume (10 ml/kg). Low volume ventilation increased lung quasi-static elastance (Est; 267 and 281%), airway (Rint; 471 and 382%) and viscoelastic resistance (Rvisc; 480 and 294%), and decreased NOe (-42 and -25%) in closed and open chest animals, respectively. After restoration of normal end-expiratory volume (EEV), Rvisc returned to control, Rint remained elevated (120 and 31%), and NOe low (-25 and -20%), whilst Est increased (23%) only in closed chest animals, being associated to interstitial edema. In contrast, after prolonged MV with normal EEV, there were no changes in lung mechanics and NOe in 16 additional closed and open chest rabbits. After prolonged MV, TNF was undetectable in serum, while its concentration in BALF was low (48 pg/ml) and similar in all groups of animals. Thus, cyclic opening-closing of peripheral airways and uneven stresses with low volume MV, that cause epithelial damage and rupture of alveolar-bronchiolar attachments (D'Angelo, E. et al. J Applied Physiol 2004; 97:260-268), result in reduced NOe and increased Rint. These alterations are not mediated by a proinflammatory process as indexed by TNF levels.