HYPERACUTE LUNG REJECTION IN A PIG-TO-HUMAN TRANSPLANT MODEL - THE ROLE OF ANTI-PIG ANTIBODY AND COMPLEMENT

Background. The physiology of hyperacute rejection of pig lung by huma n blood and the role of antispecies antibody and complement in this ph enomenon have not previously been characterized, Methods. Human blood was perfused through an ex vivo pig heart-lung preparation. In the tre atment groups, blood was either unmodified or modified to deplete alte rnative pathway complement (heat treatment), anti-pig antibody, or bot h, Control experiments were performed with unmodified and heat-treated pig blood, Physiologic parameters, organ survival, and immunohistolog y were the primary outcome measures assessed. Results. Pig lung was co nsistently damaged by human blood within 45 min (median 20 min), as ev idenced by elevated pulmonary vascular resistance and parenchymal inju ry, Immunohistologic studies of perfused lungs showed prominent deposi tion of IgM and classical pathway component, C4, and weaker deposition of alternative pathway component, properdin, Heat treatment did not i mpede the rise in pulmonary vascular resistance or significantly prolo ng survival, Depletion of anti-pig antibody prolonged survival (median 90 min) and attenuated the rise in pulmonary vascular resistance, Ant ibody absorption, combined with heat treatment of plasma, prevented th e elevation in pulmonary vascular resistance and yielded median graft survival (210 min) similar to pig blood perfusion (similar to 240 min) . Conclusions. These results show that elevated pulmonary vascular res istance and pulmonary parenchymal injury are mediated at least in part by antispecies antibody and heat-sensitive pathways. They are consist ent with the hypothesis that complement activation contributes signifi cantly to acute lung damage in the pig-to-human species combination.