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J Appl Physiol 97: 2014-2019, 2004. First published June 18, 2004; doi:10.1152/japplphysiol.00452.2004
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HIGHLIGHTED TOPICS
Lung Growth and Repair

Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury

Simone A. J. ter Horst,1 Gerry T. M. Wagenaar,1 Eveline de Boer,1 Margôt A. van Gastelen,1 Joost C. M. Meijers,2 Bart J. Biemond,3 Ben J. H. M. Poorthuis,1 and Frans J. Walther1,4

1Department of Pediatrics, Division of Neonatology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; 2Department of Vascular Medicine, and 3Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, the Netherlands; 4Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90502

Submitted 5 May 2004 ; accepted in final form 15 June 2004

Bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment modalities. Pentoxifylline, a phosphodiesterase inhibitor, inhibits multiple processes that lead to neonatal hyperoxic lung injury, including inflammation, coagulation, and edema. Using a preterm rat model, we investigated the effects of pentoxifylline on hyperoxia-induced lung injury and survival. Preterm rat pups were exposed to 100% oxygen and injected subcutaneously with 0.9% saline or 75 mg/kg pentoxifylline twice a day. On day 10, lung tissue was harvested for histology, fibrin deposition, and mRNA expression, and bronchoalveolar lavage fluid was collected for total protein concentration. Pentoxifylline treatment increased mean survival by 3 days (P = 0.0018) and reduced fibrin deposition by 66% (P < 0.001) in lung homogenates compared with untreated hyperoxia-exposed controls. Monocyte chemoattractant protein-1 expression in lung homogenates was decreased, but the expressions of TNF-{alpha}, IL-6, matrix metalloproteinase-12, tissue factor, and plasminogen activator inhibitor-1 were similar in both groups. Total protein concentration in bronchoalveolar lavage fluid was decreased by 33% (P = 0.029) in the pentoxifylline group. Pentoxifylline treatment attenuates alveolar fibrin deposition and prolongs survival in preterm rat pups with neonatal hyperoxic lung injury, probably by reducing capillary-alveolar protein leakage.

hyperoxia; inflammation; coagulation; newborn rat; bronchopulmonary dysplasia


Address for reprint requests and other correspondence: G. T. M. Wagenaar, Dept. of Pediatrics, Division of Neonatology, Leiden Univ. Medical Center, P3-25, PO Box 9600, 2300 RC, Leiden, the Netherlands (E-mail: G.T.M.Wagenaar{at}lumc.nl).




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