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Dependence of lung injury on inflation rate during low-volume ventilation in normal open-chest rabbits

Istituto di Fisiologia Umana I, Università di Milano, 20133 Milan; Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, 35128 Padua, Italy; and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H2X 2P2

Submitted 3 November 2003 ; accepted in final form 10 March 2004

Lung mechanics and morphometry were assessed in two groups of nine normal open-chest rabbits mechanically ventilated (MV) for 3–4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (VT; 11 ml/kg) and high (group A) or low (group B) inflation flow (44 and 6.1 ml·kg^–1·s^–1, respectively). Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH₂O), MV on ZEEP increased quasi-static elastance and airway and viscoelastic resistance more in group A (+251, +393, and +225%, respectively) than in group B (+180, +247, and +183%, respectively), with no change in viscoelastic time constant. After restoration of PEEP, quasi-static elastance and viscoelastic resistance returned to control, whereas airway resistance, still relative to initial values, remained elevated more in group A (+86%) than in group B (+33%). In contrast, prolonged high-flow MV on PEEP had no effect on lung mechanics of seven open-chest rabbits (group C). Gas exchange on PEEP was equally preserved in all groups, and the lung wet-to-dry ratios were normal. Relative to group C, both groups A and B had an increased percentage of abnormal alveolar-bronchiolar attachments and number of polymorphonuclear leukocytes in alveolar septa, the latter being significantly larger in group A than in group B. Thus prolonged MV on ZEEP with cyclic opening-closing of peripheral airways causes alveolar-bronchiolar uncoupling and parenchymal inflammation with concurrent, persistent increase in airway resistance, which are worsened by high-inflation flow.

lung mechanics; viscoelasticity; recruitment-derecruitment of lung units; airway-parenchymal coupling; parenchymal inflammation

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