Reduced Surfactant Contributes to Increased Lung Stiffness Induced by Rapid Inspiratory Flow

Introduction: The mechanism of fast inspiratory flow rate (V_I′) induced lung injury is unclear. As fast V_I′ increases hysteresis, a measure of surface tension at the air–liquid interface, surfactant release or function may be important. This experimental study examines the contribution of impaired surfactant release or function to dynamic-VILI. Methods: Isolated perfused lungs from male Sprague Dawley rats were randomly allocated to four groups: a long or short inspiratory time (Ti = 0.5 s; slow V_I′ or Ti = 0.1 s; fast V_I′) at PEEP of 2 or 10 cmH₂O. Tidal volume was constant (7 ml/kg), with f = 60 breath/min. Forced impedance mechanics (tissue elastance (Htis), tissue resistance (Gtis) and airway resistance (Raw) were measured at 30, 60 and 90 min following which the lung was lavaged for surfactant phospholipids (PL) and disaturated PL (DSP). Results: Fast V_I′ resulted in a stiffer lung. Concurrently, PL and DSP were decreased in both tubular myelin rich and poor fractions. Phospholipid decreases were similar with PEEP. In a subsequent cohort, laser confocal microscopy-based assessment demonstrated increased cellular injury with increased V_I′ at both 30 and 90 min ventilation. Conclusion: Rapid V_I′ may contribute to ventilator induced lung injury (VILI) through reduced surfactant release and/or more rapid reuptake despite unchanged tidal stretch.