Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival

Denner, J.; Laengin, M.; Reichart, B.; Krueger, L.; Fiebig, U.; Mokelke, M.; Radan, J.; Mayr, T.; Milusev, A.; Luther, F.; Sorvillo, N.; Rieben, R.; Brenner, P.; Walz, C.; Wolf, E.; Roshani, B.; Stahl-Hennig, C.; Abicht, J.-M.

doi:10.1101/2020.04.07.029702

bioRxiv · 10.1101/2020.04.07.029702

Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival

Denner, J.·Laengin, M.·Reichart, B.·Krueger, L.·Fiebig, U.·Mokelke, M.·Radan, J.·Mayr, T.·Milusev, A.·Luther, F.·Sorvillo, N.·Rieben, R.·Brenner, P.·Walz, C.·Wolf, E.·Roshani, B.·Stahl-Hennig, C.·Abicht, J.-M.

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Abstract

Xenotransplantation using pig organs has achieved survival times of more than 195 days in pig orthotopic heart transplantation into baboons. Here we demonstrate that in addition to an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth of the transplant, prevention of transmission of the porcine cytomegalovirus (PCMV) plays an important role in achieving long survival times. For the first time we demonstrate that PCMV transmission in orthotopic pig heart xenotransplantation was associated with a reduced survival time of the transplant and increased levels of IL-6 and TNF were found in the transplanted baboon. Furthermore, high levels of tPA-PAI-1 complexes were found, suggesting a complete loss of the pro-fibrinolytic properties of the endothelial cells. These data show that PCMV has an important impact on transplant survival and call for elimination of PCMV from donor pigs.

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Denner, J., Laengin, M., Reichart, B., Krueger, L., Fiebig, U., Mokelke, M., Radan, J., Mayr, T., Milusev, A., Luther, F., Sorvillo, N., Rieben, R., Brenner, P., Walz, C., Wolf, E., Roshani, B., Stahl-Hennig, C., Abicht, J.-M.. 2020-04-08. Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival. https://doi.org/10.1101/2020.04.07.029702

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