Objectives:Ventilation with positive end-expiratory pressure (PEEP) above the inflection point (Pinf) has been shown to reduce lung injury by recruiting previously closed alveolar regions; however, it carries the risk of hyperinflating the lungs. The present study examined the hypothesis that a new strategy of recruiting the lung with a sustained inflation (SI), followed by ventilation with small tidal volumes, would allow the maintenance of low PEEP levels (<Pinf) without inducing additional lung injury.Design:Prospective, randomized, controlledex vivostudy.Setting:An animal laboratory in a university setting.Subjects:Isolated nonperfused lungs of adult Sprague-Dawley rats.Interventions:We studied the effect on compliance and lung injury in four groups (n = 10 per group) of lavaged rat lungs. One group (group 1) served as a control; their lungs were inflated at PEEP < Pinfbut not ventilated. The other three groups were ventilated with small tidal volumes (5 to 6 mL/kg) for 2 hrs with the following interventions: group 2, PEEP < Pinfwithout SI; group 3, PEEP < Pinfafter a SI to 30 cm H2O for 30 secs; and group 4, PEEP > Pinf.Measurements and Main Results:In groups 2 and 4, static compliance decreased after ventilation (p< .01). Histologically, group 2 (PEEP < Pinfwithout SI) showed significantly greater injury of small airways, but not of terminal respiratory units, compared with group 1. Group 3 (PEEP < Pinfafter a SI), but not group 4, showed significantly less injury of small airways and terminal respiratory units compared with group 2.Conclusions:We conclude that small tidal volume ventilation after a recruitment maneuver allows ventilation on the deflation limb of the pressure/volume curve of the lungs at a PEEP < Pinf. This strategy a) minimizes lung injury as well as, or better than, use of PEEP > Pinf, and b) ensures a lower PEEP, which may minimize the detrimental consequences of high lung volume ventilation.