Introduction: Cardiac xenotransplantation is a promising alternative to allotransplantation. While recent progress has led to increased survival, acute vascular rejection remains a challenge. The endothelial glycocalyx, a crucial regulator of endothelial health and inflammation, is implicated in allograft rejection. However, its role in xenotransplantation is not well understood. This study retrospectively analyzed peri- and postoperative plasma levels of hyaluronan (HA), heparan sulfate (HS), and syndecan-1 (Sdc-1) as surrogate markers for endothelial glycocalyx integrity in a pig-to-baboon cardiac xenotransplantation model.
Methods: Plasma samples from n=4 baboons undergoing orthotopic pig heart transplantation were analyzed in the peri- and postoperative period using ELISA. These n=4 experiments were divided into two groups in the postoperative period: experiments, that were deliberately terminated after 90 postoperative days (group I) and animals, which were tested positive for PCMV/PRV (group II). As probes were available for the postoperative period (but no perioperative probes were available any more), a fifth baboon was analyzed in this period. In this animal, the xenograft was ischemically preserved and no growth-inhibiting drugs were administered.
Results: Perioperatively, HA levels transiently increased, while HS and Sdc-1 decreased in all n=4 animals, suggesting some glycocalyx shedding, albeit potentially less pronounced than in comparable human cardiac surgery settings. In contrast to the human cardiac surgery setting, no correlation was found between perioperative lactate and glycocalyx component changes. Postoperatively, group I animals showed stable glycocalyx component levels. In contrast, animals with PCMV/PRV infection exhibited a marked increase in HA and Sdc-1, and a decrease in HS. The animal with graft overgrowth also showed increased HA and Sdc-1 and decreased HS levels.
Conclusion: This study provides first insights into endothelial glycocalyx dynamics in pig-to-baboon cardiac xenotransplantation. Using current strategies of cardiac xenotransplantation, damage of the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings. At the same time, the data from experiments where current strategies, like PCMV/PRV elimination, non-ischemic preservation and growth inhibition, could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.