Ex-vivo hemoperfusion (eHPS) of pig-lungs with whole human blood: effects of complement inhibition with a soluble C1-esterase-inhibitor.
OBJECTIVE
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 HAR in the lung. After standardizing the model, the effect of a soluble complement inhibitor (C1-INH, Berinert) was investigated.


METHODS
Pig lungs were harvested following cold perfusion with Celsior preservation solution. EHP was performed using fresh heparinized human blood plus C1-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 evaluated.


RESULTS
BGA, PAP, macroscopic and microscopic changes in the control group showed HAR, while the C1-INH group showed significantly longer function. Leucocytes and platelets were markedly activated in the control, whereas 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 C1-INH. Immunohistochemistry showed less C1q, C3, C5b-9 activation in the C1-INH group.


CONCLUSIONS
Investigation of interaction of human blood with pig lung endothelium could be done in this model. C1-INH attenuates HAR in a pig-to-human lung transplantation model by decreasing the activation of adhesion molecules. C1-INH could play a role in induction therapy of future lung xenotransplantation.
Schelzig
H
H
University of Ulm, Dept. of Thoracic and Vascular Surgery, Germany. hubert.schelzig@medizin.uni-ulm.de
Simon
F
F
Krischer
C
C
Vogel
A
A
Abendroth
D
D
D000818:Animals; D001803:Blood Transfusion; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006464:Hemoperfusion / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology / Q000473:pathology; D055370:Lung Injury; D016040:Lung Transplantation; D012995:Solubility; D013552:Swine / Q000276:immunology*; D014183:Transplantation, Heterologous
D003174:Complement C1 Inactivator Proteins