Early graft dysfunction remains a significant problem in clinical lung
transplantation, pentoxifylline, a methylxanthine derivative, has bee
n shown to have various beneficial effects on neutrophil-induced lung
injury. We investigated effects of pentoxifylline on early posttranspl
antation lung function in a canine allograft model. Ten dogs underwent
left lung allotransplantation. Donor lungs were flushed with modified
Euro-Collins solution (50 mL/kg) and stored in an inflated state for
18 hours at 1 degrees C. In five experiments (group I), pentoxifylline
was added to the flush and storage solutions (200 mg/L) at the time o
f harvest. The recipient animals received pentoxifylline (20 mg/kg int
ravenously) before reperfusion followed by pentoxifylline (0.1 mg . kg
(-1) . min(-1) intravenously) during the 6-hour posttransplantation as
sessment period. In group II, donors and recipients received no pentox
ifylline. To evaluate only allograft function, the right main pulmonar
y artery and bronchus were ligated immediately after implantation. For
6 hours thereafter hemodynamics and gas exchange were assessed at 15-
minute intervals while the animal was ventilated at an inspired oxygen
fraction of 1.0. After 1 hour of assessment there was a significant d
ifference in gas exchange between the groups, which persisted until th
e end of the study. By the end of the 6-hour assessment, the mean arte
rial oxygen tension was 236.7 mm Hg for group I versus 101.1 mm Hg for
group II (p < 0.01), and the alveolar-arterial oxygen difference was
443.1 mm Hg versus 562.2 mm Hg (p < 0.015). Hemodynamics were not diff
erent between groups. Significant differences in wet-to-dry weight rat
io (group I versus group II, 7.0 +/- 0.2 versus 8.3 +/- 0.4; p < 0.05)
and myeloperoxidase activity assay (group I versus group II, 0.145 +/
- 0.012 versus 0.201 +/- 0.016 U/mg; p < 0.05) were observed. We concl
ude that pentoxifylline improves early postoperative lung allograft fu
nction by attenuating neutrophil mediated ischemia-reperfusion injury.