Effects of intravenous and intratracheal pentoxifylline on histopathologic changes and wet-dry ratio in HCl acid-induced acute lung injury in rabbits

Introduction

The aim of this study was to compare the effects of intravenous (IV) and intratracheal (IT) pentoxfylline (PTX) on histopathologic changes and wet/dry ratio in acute lung injury in rabbits.

Methods

Twenty-one New Zealand rabbits were randomly divided into three groups (n = 7). After rabbits were sedated with IM ketamine, tracheostomy was performed and endotracheal tube was inserted. Anesthesia was maintained with continuous infusion of ketamine and atracurium. All animals were ventilated with PC mode for 3 hours and the parameters of ventilation were FiO₂: 1.0, PIP: 15 cmH₂O, PEEP: 5 cmH₂O. RR was adjusted to produce initial PaCO₂ of 35–40 mmHg. IT HCl (2 ml/kg) was given following tracheostomy in all animals. Five minutes after the application of HCl; Group 1, received IV PTX (20 mg/kg, bolus); Group 2, received IT PTX (20 mg/kg, bolus); Group 3, no treatment. At the end of 3 hours, the rabbits were sacrificed for histopathologic examination to evaluate lung injury and to measure wet/dry ratio. Tissue sections were examined for light microscopy with HE stain. The pathologic lesions were classified ranging from 0 to 4. Right lung was dried at 60°C for 24 hours. These conditions remove virtually all gravimetrically detectable water. The lung wet and dry weights were measured, and wet-to-dry weight ratio was calculated to asses pulmonary edema. Data were compared by Mann–Whitney U test. P < 0.05 was considered to indicate statistical significance.

Results

Significant changes in histopathologic findings on bronchial epithelial injury, neutrophil infiltration-density, hemorrhage and hyalen membrane were encountered in group 3 when compared with other groups (P < 0.01). There was no significance difference for septum injury and atelectasia. Wet/dry ratio of group 3 was higher than the other groups (P < 0.01).

Conclusion

PTX given after the 5 min of HCl application via IT route might have beneficial effects on histopathologic changes and wet/dry ratio in HCl induced-ALI model.