EFFECT OF PENTOXIFYLLINE IN THE VOLUME INDUCED LUNG INFLAMMATION

Xianyu S.¹, Suguihara C.², Huang J.³, Hehre D⁴, Devia C⁵ and Bancalari E⁶

¹ People’s Hospital of Hainan Province, Haikou, P. R. China

^{2, 3, 4, 5, 6}School of Medicine, University of Miami, Miami, USA.

Objective: To evaluate the efficacy of Pentoxifylline (PTX) in the attenuation of lung inflammation induced by ventilation with large tidal volumes.

Methods: 17 newborn piglets were anesthetized, tracheotomized, paralyzed, and mechanically ventilated with a constant tidal volume of 50 ml/kg for a period of 8 h. Animals were randomly assigned to a treatment group (n=8) that received PTX (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h) before and during exposure to the volume induced lung damage, or a control group (n=9) which received saline. Serum and tracheoalveolar fluid (TAF) thromboxane levels (TXB₂) were obtained before and after administration of PTX or saline and at 2h intervals thereafter until completion of the 8 h study period. Lung tissue myeloperoxidase (MPO), wet to dry lung weight and lung inflammation on pathological specimens (using a standardized scoring system) were assesses upon completion of the 8 h study. Data (mean ± SE) were analyzed using ANOVA and Chi square.

Results: A marked increase in TAF TXB₂ (Control group vs PTX group: from baseline: 13.4±13.6 to 8 h: 96.6±110.6 vs from baseline: 12.65±8.34 to 8 h: 16.15±13.42 pg/ml, p<0.03), lung edema (wet/dry: 7.52±0.67 vs 6.77±0.64, p<0.04, pathology score≥1: 8/8 vs 4/8) and neutrophil activity (MPO: 13321±3416 vs 7221±2642 OD/g, p<0.005) was observed after 8 h of high tidal volume ventilation in the saline treated animals. This inflammatory process appears to be localized within the lung since serum TXB₂ level did not change in either group (from baseline: 7.81±4.23 to 8 h: 9.63±8.13 vs from baseline: 10.10±8.75 to 8 h: 8.93±6.52 pg/ml, no significant difference.

Conclusion: A significant reduction in the pulmonary inflammatory response was observed during large tidal volume ventilation in the animals treated with PTX. These results suggest that PTX may be effective in ameliorating lung inflammation associated with mechanical ventilation in neonates.

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