Objectives: Xenotransplantation could be a future alternative to allotransplantation due to increasing organ shortage. Complement activation plays a major role in hyperacute rejection (HAR) in pig-to-human combinations. We developed an ex-vivo hemoperfusion (EHP) system to investigate pathophysiology of HARin the lung. After standardizing the model, the effect of a soluble complement inhibitor (C I-INH, Berinert'M) was investigated. Methods: Pig lungs were harvested following cold perfusion with Celsior'M preservation solution. EHP was performed using fresh heparinized human blood plus C I-INH (n=6) or heparinized human blood as control (n=4). Bloodgas analyses (BGA), pulmonalarterial pressure (PAP) were monitored. P-selectin and L-selectin were measured. Tissue samples were taken and microscopic changes evall!ated. Results: BGA, PAP, macroscopic and microscopic changes in the control group showed HAR, while the C I-INH group showed significantly longer function. Leucocytes and platelets were markedly activated in the control, wereas in the treated group L-selectin and P-selectin values indicated lower activation. HE stainings showed maintained lung architecture after perfusion of pig-lungs with human blood plus C I-INH. Immunohistochemistry showed less C Iq, C3, CSb-9 activation in the C I-INH group. Conclusions: Investigation of interaction of human blood with pig lung endothelium could be done in this model. C I-INH attenuates HAR in a pig-to-human lung transplantation model by decreasing the activation of adhesion molecules. C I-INH could playa role in induction therapy of future lung xenotransplantation.

Keywords: model, Xenotransplantation, complement inhibition