COMPLEMENT ACTIVATION AS A CAUSE FOR PRIMARY GRAFT FAILURE IN AN ISOGENEIC RAT MODEL OF HYPOTHERMIC LUNG PRESERVATION AND TRANSPLANTATION

Although agents that inhibit complement activation may be beneficial i n discordant xenotransplantation, it is not known whether local comple ment activation occurs and is deleterious after isogeneic lung transpl antation, Lungs were harvested from Lewis rats subjected to 4 degrees C 6-hr preservation followed by transplantation into strain-, gender-, and weight-matched recipients, Transplanted lungs demonstrated increa sed immunostaining for C5b-9 compared with nontransplanted controls, c onfirming local complement activation in this isograft model, To inves tigate the physiologic relevance of complement activation in the trans planted lung, the native pulmonary artery was ligated after transplant ation, and pulmonary vascular resistance (mmHg/ml/min), arterial oxyge nation (mmHg), graft neutrophil infiltration (myeloperoxidase activity , Delta Abs 460 nm/min), and recipient survival were measured at 30 mi n, Animals received either saline (control; n=22) or soluble complemen t receptor type-1 (sCR1, 15 mg/kg; n=19) 2 min before reperfusion, Ani mals treated with sCR1 showed a marked reduction in serum complement h emolytic activity (CH50; 90% lower than that of control animals, P<0.0 01), Compared with controls, sCR1-treated animals showed reduced pulmo nary vascular resistance (2.9+/-1.1 vs, 8.5+/-1.5 mmHg/ml/min, P<0.05) , improved arterial oxygenation (194+/-34 vs, 91+/-17 mmHg, P<0.05), d ecreased neutrophil infiltration (35% decrease, P<0.005), and improved recipient survival (74% vs, 23%, P<0.005), In parallel with the reduc tion in complement hemolytic activity in sCR1-treated animals, immunoh istology of the transplanted lung revealed decreased C5b-9 deposition compared with controls, Taken together, these data indicate that compl ement activation occurs after lung preservation and transplantation in an isograft model, and that inhibiting complement activation improves outcome after transplantation.