Keratinocyte growth factor prevents ventilator-induced lung injury in an ex vivo rat model

Mechanical ventilation has been shown to produce lung injury characterized by noncardiogenic pulmonary edema, Keratinocyte growth factor (KGF) is a he parin-binding growth factor that causes alveolar type II pneumocyte hyperpl asia, KGF pretreatment and the resultant pneumocyte hyperplasia reduce flui d flux in models of lung injury. We utilized the isolated perfused rat lung model to produce lung injury by varying tidal volume and the level of posi tive end-expiratory pressure during mechanical ventilation. Pretreatment wi th KGF attenuated ventilator-induced lung injury (VILI). This was demonstra ted by lower wet-to-dry lung weight ratios and less lung water accumulation in the KGF group. Further, KGF prevented the decline in dynamic compliance and alveolar protein accumulation in VILI, KGF pretreatment reduced alveol ar accumulation of intravascularly administered fluorescein isothiocyanate- labeled high-molecular-weight dextran. Thus, pretreatment with KFG attenuat es injury in this ex vivo model of VILI via mechanisms that prevent increas es in permeability.