Changes in proteoglycans and lung tissue mechanics during excessive mechanical ventilation in rats

Abstract

Excessive mechanical ventilation results in changes in lung tissue mechanics. We hypothesized that changes in tissue properties might be related to changes in the extracellular matrix component proteoglycans (PGs). The effect of different ventilation regimens on lung tissue mechanics and PGs was examined in an in vivo rat model. Animals were anesthetized, tracheostomized, and ventilated at a tidal volume of 8 (Vt 8), 20, or 30 (Vt 30) ml/kg, positive end-expiratory pressure of 0 (PEEP0) or 1.5 (PEEP1.5) cmH2O, and frequency of 1.5 Hz for 2 h. The constant-phase model was used to derive airway resistance, tissue elastance, and tissue damping. After physiological measurements, one lung was frozen for immunohistochemistry and the other was reserved for PG extraction and Western blotting. After 2 h of mechanical ventilation, tissue elastance and damping were significantly increased in rats ventilated at Vt 30PEEP0 compared with control rats (ventilated at Vt 8PEEP1.5). Versican, basement membrane heparan sulfate PG, and biglycan were all increased in rat lungs ventilated at Vt 30PEEP0 compared with control rats. At Vt 30PEEP0, heparan sulfate PG and versican staining became prominent in the alveolar wall and airspace; biglycan was mostly localized in the airway wall. These data demonstrate that alterations in lung tissue mechanics with excessive mechanical ventilation are accompanied by changes in all classes of extracellular matrix PG.