Abstract

Objective: Reperfusion injury (RI) is the main reason for early graft failure after lung transplantation. Inhibition of the adherence of polymorphonuclear leucocytes (PMN) to activated endothelium by blocking L- and E-selectins (antibody EL-246) could ameliorate RI.

Methods: Reproducible RI was induced in a left lung autotransplant model in sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 hours in situ at 15°C. After reperfusion right main bronchus and pulmonary artery were crossclamped leaving the animal dependent on the reperfused lung (standard procedure). Pulmonary function was assessed by AaDO₂ (mm Hg) and PVR (dyn.s.cm^-5), the chemiluminescence (CL) of isolated PMN (× 10³counts/250000 cells) served as indicator of PMN activation.

Control animals (n = 6) underwent hilar stripping only. 'Untreated' animals (n = 6) underwent the standard procedure (standard group). EL-246 group animals (n = 6) were treated additionally with 1 mg/kg BW of EL-246 given prior and during reperfusion. Results were analysed by MANOVA or Friedmann's ANOVA (*: statistical significance, p <= 0.05; mean ± SEM).

Results: After 3 hours of reperfusion 5 animals in the standard group developed alveolar edema compared to 1 animal in both control and EL-246 groups (p < 0.05). AaDO₂ was significantly increased in the standard group compared to both control and EL-246 groups (510 ± 67 vs. 230 ± 43 and 199 ± 35 resp.). PVR was significantly increased in the standard group compared to both control and EL-246 groups (656 ± 83 vs. 353 ± 75 and 317 ± 31 resp.). CL values were significantly lower in the standard group compared to control and EL-246 groups (753 ± 585 vs. 2339 ± 751 and 2234 ± 877 resp.).

Conclusions: Treatment with EL-246 results in improved pulmonary function and less PMN activation in this experimental model. Further studies are necessary to evaluate the possible role of selectin blockade in amelioration of RI in human lung transplantation.