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J Appl Physiol (March 10, 2005). doi:10.1152/japplphysiol.01368.2004
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Submitted on December 10, 2004
Accepted on March 4, 2005

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

Edgardo D'Angelo1*, Matteo Pecchiari1, Patrizia Della Valle2, Antonia Koutsoukou3, and Joseph Milic-Emili

1 Istituto di Fisiologia Umana I, Universita' degli Studi di Milano, Milan, Italy
2 Servizio di Coagulazione & Unita' di Ricerca Trombosi, IRCCS Ospedale San Raffaele, Milan, Italy
3 Critical Care Department, University of Athens, Athens, Greece

* To whom correspondence should be addressed. E-mail: edgardo.dangelo{at}unimi.it.

Lung mechanics, exhaled NO (NOe), and tumor necrosis factor (TNF-{alpha}) in serum and bronchoalveolar lavage (BAL) fluid were assessed in 8 closed and 8 open chest, normal anesthetized rabbits undergoing prolonged (3-4 h) mechanical ventilation (MV) at low volume with physiologic tidal volumes (10 ml.kg-1). Relative to initial MV on positive end-expiratory pressure (PEEP), MV at low volume increased lung quasi-static elastance (Est; +267 and +281%), airway (Rint; +471 and +382%) and viscolelastic resistance (Rvisc; +480 and +294%), and decreased NOe (-42 and -25%) in closed and open chest rabbits, respectively. After restoration of PEEP, Rvisc returned to control, while Rint remained elevated (+120 and +31%), and NOe low (-25 and -20%) in both groups of rabbits. Est remained elevated (+23%) only in closed chest animals, being associated with interstitial pulmonary edema, as reflected by increased lung wet/dry ratio with normal albumin concentration in BAL fluid. In contrast, in 16 additional closed and open chest rabbits there were no changes of lung mechanics or NOe after prolonged MV on PEEP only. At the end of prolonged MV, TNF-{alpha} was practically undetectable in serum, while its concentration in BAL fluid was low and similar in animals subjected or not subjected to ventilation at low volume (62 vs 43 pg.ml-1). These results indicate that mechanical injury of peripheral airways due to their cyclic opening and closing during ventilation at low volume results in changes in lung mechanics and reduction in exhaled NO, and that these alterations are not mediated by a proinflammatory process as this is expressed by TNF-{alpha} levels.




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