Abstract
The pathophysiology of xenograft hyperacute rejection is still poorly understood although it is believed to involve complement fixation to vascular endothelium, probably as a result of the presence of naturally occurring anti-species antibodies. Hyperacute rejection of pig hearts by human blood was studied in an ex-vivo working heart model. Cardiac performance and immunological reactions occurring in the perfusing blood were studied. Stroke work performed by pig hearts perfused with human blood and their survival (median 47 min: n = 10) was significantly reduced compared to survival (median 158 min: n = 10) and stroke work performed by pig hearts perfused with pig blood. Decomplementation of human blood resulted in improved performance and duration of the action (median survival > 240 min: n = 10) of hearts. Quantitative differences were seen in complement fixation between the groups. Our data demonstrate the central role of complement in the destruction of pig-to-man xenografts.
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