title: Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury.
abstract: 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.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Leiden Univ. Medical Center, P3-25, PO Box 9600, 2300 RC, Leiden, the Netherlands.
authors.forename: Simone A J
authors.initials: SA
authors.lastname: ter Horst
authors.forename: Gerry T M
authors.initials: GT
authors.lastname: Wagenaar
authors.forename: Eveline
authors.initials: E
authors.lastname: de Boer
authors.forename: Margôt A
authors.initials: MA
authors.lastname: van Gastelen
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Biemond
authors.forename: Ben J H M
authors.initials: BJ
authors.lastname: Poorthuis
authors.forename: Frans J
authors.initials: FJ
authors.lastname: Walther
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018932:Chemokine CCL2 / Q000235:genetics; D005337:Fibrin / Q000037:antagonists & inhibitors*; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D005337:Fibrin; D010431:Pentoxifylline