Protective Effect of Pentoxifylline on Volume-Induced Lung Injury in Newborn Piglets

Abstract

To evaluate the efficacy of pentoxifylline (PTXF) in the attenuation of lung inflammation during volume-induced lung injury (VILI) in newborn piglets, 17 newborn piglets were mechanically ventilated with a large tidal volume (50 ml/kg) for a period of 8 h. They were randomly assigned to a placebo (PL, n = 9) or a treatment group (PTXF, n = 8) that received PTXF (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h). Hemodynamics, lung mechanics and arterial blood gases were measured during the 8 h of study. Serum and tracheoalveolar fluid (TAF) platelet-activating factor (PAF) and thromboxane (TXB₂) levels were obtained at baseline and at 8 h, while lung tissue myeloperoxidase (MPO) and wet to dry weight were assessed after the completion of the study. In the PL group, a marked increase in TAF PAF and TXB₂ levels was observed only in TAF, suggesting that the inflammatory process was localized within the lungs. A significant decrease in lung tissue MPO activity (p < 0.005) and lung wet to dry weight ratio (p < 0.04) was observed in the PTXF group. There were no differences in hemodynamics, arterial blood gases or lung mechanics measurements between groups. A significant reduction in pulmonary inflammatory response was observed during VILI in the PTXF pretreated animals. These results suggest that PTXF may be effective in modulating lung inflammation associated with mechanical ventilation in neonates.

The Role of Genetic Polymorphisms in Antioxidant Enzymes and Potential Antioxidant Therapies in Neonatal Lung Disease

“…In contrast to previous observations (6), a recent study in the animal model of hyperoxic resuscitation after perinatal asphyxia suggested a potential role for N-acetylcysteine in lung protection, as it was proved to reduce lung and systemic levels of OS and inflammatory markers (111). Moreover, pentoxifillyne, a phosphodiesterase inhibitor with immunomodulatory and antifibrotic features, has been investigated in the animal model of hyperoxia, and it was proved to reduce lung edema and neutrophils influx, while it increased lung activity of SOD, CAT, and GPx (9), in agreement with previous reports of reduced inflammatory cytokines in tracheal aspirates (173) and lung protection against mechanical ventilation-induced injury (81,158). Besides antioxidant activity, pentoxyfilline also induces VEGF expression and enhances pulmonary vasculature development (9), which could be a major issue for the prevention of BPD-associated vascular abnormalities.…”

Strategies to minimize lung injury in extremely low birth weight infants

“…Recentemente, tem sido demonstrado na literatura que mediadores inflamatórios, como o FNT-alfa e as interleucinas, aumentam durante a ventilação mecânica, principalmente quando se empregam volumes correntes elevados 13,14,[21][22][23][24][25] . Naik et al observaram que o início da ventilação mecânica em ovelhas prematuras desencadeou o aumento dos níveis de mediadores inflamatórios, sugerindo que bastam alguns ciclos de ventilação mecâ-nica no prematuro para causar a lesão pulmonar 15 .…”

Pentoxifylline and prevention of hyperoxia-induced lung ­injury in neonatal rats

“…Studies in rabbits have shown increased levels of CAT, SOD, and GPX during ischemia and reperfusion injury after PTX treatment (17). Studies have also shown that PTX is able to attenuate lung injury related to mechanical ventilation and meconium (18,19). In neonatal HILI models, PTX treatment decreased IL-6 concentration in bronchoalveolar lavage (20), reduced alveolar fibrin deposition, and prolonged survival (21).…”