REDUCTION OF ISCHEMIA-REPERFUSION INJURY BY PENTOXIFYLLINE IN THE ISOLATED RAT LUNG

Inhibition of pulmonary neutrophil sequestration attenuates ischemia-r eperfusion (IR) lung injury. Pentoxifylline (PTX) reduced pulmonary se questration of neutrophils and neutrophil-dependent lung injury in sev eral experimental settings but has never been tested in IR models. We hypothesized that PTX may have a beneficial effect on IR lung injury a s measured by the coefficient of filtration (K-fc) and may reduce IR a ssociated sequestration of neutrophils as assessed by lung myeloperoxi dase (MPO) activity and by blood neutrophil count decrease during repe rfusion. Three groups of isolated blood perfused rat lungs were studie d: a time control group (n = 6) was perfused for 3 h, and two groups ( n = 10) subjected to 1 h ischemia were treated with PTX or saline befo re a 2 h reperfusion. The increase in K-fc induced by IR was reduced f ivefold by PTX compared with saline (+27 +/- 8% versus +112 +/- 12%, r espectively; p < 0.001), and was similar to time controls (+9 +/- 9%). After IR, MPO and blood neutrophil count decrease were lower with PTX than with saline. Changes in K-fc were correlated to the percentage d ecrease in blood neutrophils during reperfusion. We conclude that PTX reduced rat lung IR microvascular injury. This effect may be mainly ca used by decrease in lung sequestration of neutrophils during reperfusi on.