Pentoxifylline in flush solution improves early lung allograft function

Abstract

Postischemic ischemia reperfusion injury is a frequent and unpredictable problem in clinical lung transplantation. Pentoxifylline (PTX) has a number of effects that could decrease reperfusion injury: reduced neutrophil adhesion to endothelium, decreased production of tumor necrosis factor, decreased platelet aggregation, and increased production of vasodilatory prostaglandins by vascular endothelium. We have demonstrated previously that PTX administered before storage and again during reperfusion reduced lung reperfusion injury. The purpose of the present study was to determine whether these observations were storage or reperfusion effects. Fourteen canine left lung allotransplantations were performed. Donor lungs were flushed with modified Euro-Collins solution and stored for 24 hours at 1 degree C. Immediately after transplantation, the contralateral right main pulmonary artery and bronchus were ligated to assess isolated allograft function. Hemodynamic indices and arterial blood gas analysis (inspired oxygen fraction 1.0) were assessed for 6 hours before sacrifice. Allograft myeloperoxidase activity was assessed. Bronchoalveolar lavage fluid was obtained from the allograft middle lobe for neutrophil counts. The animals were divided into three groups based on the timing of PTX administration. Group 1 (n = 5) animals received no PTX. Group 2 (n = 4) animals received PTX (20 mg/kg) just before reperfusion as well as continuous infusion (0.1 mg x kg-1 x min-1) during the assessment period. In group 3 (n = 5), donor lungs received PTX (200mg/L) in the flush solution only. Superior gas exchange was noted in the lungs receiving PTX only in the flush solution (group 3). Myeloperoxidase activity in group-3 allografts was significantly reduced. In addition, protein levels and neutrophil counts in the bronchoalveolar lavage fluid were significantly reduced in group-3 allografts. Pentoxifylline ameliorates lung allograft reperfusion injury when administered in the flush solution. Our data suggest that PTX will prevent graft endothelial dysfunction during 24-hour cold ischemic storage and consequently will prevent neutrophil activation and migration into lung tissue.