Keratinocyte growth factor attenuates hydrostatic pulmonary edema in an isolated, perfused rat lung model.
Hydrostatic pulmonary edema is a common complication of congestive heart failure, resulting in substantial morbidity and mortality. Keratinocyte growth factor (KGF) is a mitogen for type II alveolar epithelial and microvascular cells. We utilized the isolated perfused rat lung model to produce hydrostatic pulmonary edema by varying the left atrial and pulmonary capillary pressure. Pretreatment with KGF attenuated hydrostatic edema formation. This was demonstrated by lower wet-to-dry lung weight ratios, histological evidence of less alveolar edema formation, and reduced alveolar accumulation of intravascularly administered FITC-labeled large-molecular-weight dextran in rats pretreated with KGF. Thus KGF attenuates injury in this ex vivo model of hydrostatic pulmonary edema via mechanisms that prevent increases in alveolar-capillary permeability.
Welsh
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Department of Medicine, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA. dwelsh@lsuhsc.edu
Guery
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Deboisblanc
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Dobard
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Creusy
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Mercante
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Nelson
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Summer
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Mason
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D000818:Animals; D001794:Blood Pressure; D002196:Capillaries / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D003911:Dextrans / Q000493:pharmacokinetics; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006874:Hydrostatic Pressure; D066298:In Vitro Techniques; D008297:Male; D009929:Organ Size; D010477:Perfusion; D011650:Pulmonary Alveoli / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D003911:Dextrans; C496455:Fgf7 protein, rat; C015219:fluorescein isothiocyanate dextran; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D016650:Fluorescein-5-isothiocyanate