Low Tidal Volume Reduces Epithelial and Endothelial Injury in Acid-injured Rat Lungs

Abstract

Using a rat model of acid-induced lung injury, we tested the hypothesis that tidal volume reduction at the same level of PEEP (10 cm H 2 O) would diminish the degree of pulmonary edema by attenuating injury to the alveolar epithelial and endothelial barriers. Tidal volume reduction from 12 to 6 to 3 ml/kg significantly reduced the rate of lung water accumulation from 690 l/h to 310 l/h to 210 l/h. Ventilation with either 6 or 3 ml/kg reduced endothelial injury equally as measured by plasma vWf:Ag and permeability to albumin. Plasma RTI40, a marker of type I epithelial cell injury, decreased 46% when tidal volume was reduced from 12 to 6 ml/kg and decreased an additional 33% with 3 ml/kg (p Ͻ 0.05). The rate of alveolar epithelial fluid clearance was significantly faster in the 3-ml/kg group (24 Ϯ 7%/h) compared with 6 ml/kg (15 Ϯ 11%/h) and 12 ml/kg (3 Ϯ 6%/h). We conclude that low tidal volume ventilation protects both the alveolar epithelium and the endothelium in this model of acute lung injury. The additional decrease in pulmonary edema with a tidal volume of 3 ml/kg is partly accounted for by greater protection of the alveolar epithelium.

Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury

“…In Fig. 4, the data obtained from Frank et al 3 relating fluid clearance to decreasing V T can also be shown to fit a convex curvilinear relationship such that Jensen's inequality may also be applied. Using the same low V T protocol, it follows that a variable ventilation strategy may confer benefit with respect to recruitment from the larger breaths and fluid clearance from the smaller breaths invoking the same principle (Jensen's inequality) applied to two separate curvilinear functions: i) disproportionate lung recruitment with improved compliance and gas exchange resulting from the intermittent higher tidal volumes as applied to the convex curvilinear pressure-volume curve and ii) disproportionately greater fluid clearance resulting from the intermittent lower tidal volumes applied to the convex curvilinear fluid clearance-tidal volume curve.…”

“…Frank et al 3 showed that V T reduction to levels even below that recommended by the ARDSNet trial was associated with the greatest improvement in fluid clearance. Biologically variable ventilation is unique in that both lower (presumably advantageous) and higher (presumably disadvantageous) V T breaths are included in the modulation file.…”

“…In oleic acid (OA) injured pigs, Colmenero-Ruiz et al 2 showed decreased extravascular lung water (EVLW) when V T was reduced from 12 to 6 mLÁkg -1 . In a rat model of acid-injured lungs, Frank et al 3 showed an even greater improvement in alveolar fluid clearance and biochemical markers of epithelial and endothelial injury with further V T reduction from 12 to 3 mLÁkg -1 . Alternatively, Constantin et al 4 showed that recruitment maneuvers were associated with improved alveolar fluid clearance only in those patients in whom recruitment was sustained.…”

Role of the pulmonary epithelium and inflammatory signals in acute lung injury

“…Using a rat model of lung injury, Frank et al examined the effect of three different tidal volumes (3, 6 and 12 ml/kg) on lung injury in rats. Their investigation showed that alveolar epithelial injury was a critical part of the pathology because there were elevated plasma levels of rat type I cell 40 kD protein, a marker of type I epithelial cell injury and impaired alveolar fluid clearance, effects that were reduced by lower tidal volume ventilation [39].…”

“…Using a rat model of lung injury, Frank et al examined the effect of three different tidal volumes (3, 6 and 12 ml/kg) on lung injury in rats. Their investigation showed that alveolar epithelial injury was a critical part of the pathology because there were elevated plasma levels of rat type I cell 40 kD protein, a marker of type I epithelial cell injury and impaired alveolar fluid clearance, effects that were reduced by lower tidal volume ventilation [39].Radiographically, ALI/ARDS is a heterogeneous process, with areas of normal lung adjacent to fluid-filled alveoli [4]. Thus, normal alveolar units may be subject to much higher local distending pressures when ventilated with a given tidal volume.…”