sCR1sLeX reduces lung allograft ischemia–reperfusion injury but does not ameliorate acute rejection

Stammberger, Uz; Hamacher, Jürg; Pache, Jean-Claude; Schmid, Ralph A. (2002). sCR1sLeX reduces lung allograft ischemia–reperfusion injury but does not ameliorate acute rejection. European journal of cardio-thoracic surgery, 22(3), pp. 368-372. Elsevier Science B.V. 10.1016/S1010-7940(02)00355-X

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Background: Combined inhibition of complement and leukocyte adhesion by sCR1sLeX reduces lung allograft dysfunction up to 24 h. In the present study its effect on graft function and acute rejection was evaluated up to 5 days after experimental transplantation. Methods: Orthotopic single left lung transplantation was performed in 35 male rats (Brown Norway to Fischer 344) after a total ischemic time of 20 h. Two groups were assessed after 1, 3, and 5 days post-transplant, respectively (n=5 per group and time point): controls vs. recipients which received 10 mg/kg sCR1sLeX 15 min prior to reperfusion. In addition, five animals received 10 mg/kg per day sCR1sLeX for 5 days. For blood gas analysis of the graft, the contralateral lung was occluded for 5 min to assess graft function. Lung grafts were flushed, and histological grading was performed in blinded fashion according to the International Society for Heart and Lung Transplantation criteria. Results: Graft PaO2 in recipients treated with sCR1sLeX was superior on day 1 (383±118 vs. 56±15 mmHg; P≪0.0001) and day 3 (446±48 vs. 231±108 mmHg; P≪0.0001). Five days after transplantation, no difference in PaO2 was found (61±28 vs. 83±31 mmHg; P=0.59). Repeated treatment with sCR1sLeX for 5 days did not improve PaO2 (64±5 mmHg; P=0.65 vs. control; P=0.93 vs. sCR1sLeX). At any time point, there was no difference in the degree of rejection between groups. Conclusions: In this model sCR1sLeX provided marked improvement of graft function up to 3 days, but inhibition of both complement system and selectin dependent leukocyte adhesion failed to protect against acute rejection.

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