The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation-First Insights

Abstract

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface-the endothelial glycocalyx-are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation.

Keywords: endothelial activation; endothelial glycocalyx; heart; organ preservation; orthotopic heart transplantation; xenotransplantation.

Figure 1

Perioperative changes of hyaluronan (a,b), heparan sulfate (c,d) and syndecan-1 (e,f) in absolute values (ng/mL) and as fold increases compared to the preoperative values (left and right, respectively). (b,d,f) Mean values ± SD (n = 4). CPB, cardiopulmonary bypass; POD1, first postoperative day; XTx, xenotransplantation.

Figure 1

Perioperative changes of hyaluronan (a,b), heparan sulfate (c,d) and syndecan-1 (e,f) in absolute values (ng/mL) and as fold increases compared to the preoperative values (left and right, respectively). (b,d,f) Mean values ± SD (n = 4). CPB, cardiopulmonary bypass; POD1, first postoperative day; XTx, xenotransplantation.

Figure 2

Perioperative courses of serum lactate in absolute values (ng/mL) and as fold increases compared to start of surgery (a,b). Correlation between perioperative lactate levels and changes of hyaluronan (c), heparan sulfate (d) and syndecan-1 (e). (b), mean values ± SD (n = 4). CPB, cardiopulmonary bypass; POD1, first postoperative day; XTx, xenotransplantation.

Figure 2

Perioperative courses of serum lactate in absolute values (ng/mL) and as fold increases compared to start of surgery (a,b). Correlation between perioperative lactate levels and changes of hyaluronan (c), heparan sulfate (d) and syndecan-1 (e). (b), mean values ± SD (n = 4). CPB, cardiopulmonary bypass; POD1, first postoperative day; XTx, xenotransplantation.

Figure 3

Postoperative courses of hyaluronan (a), heparan sulfate (b) and syndecan-1 (c) plasma concentrations. Group I, experiments deliberately terminated after 90 postoperative days with the baboons in excellent clinical condition, mean values ± SEM (n = 2); Group II, baboons with PCMV/PRV infections, mean values ± SEM (n = 2). PCMV/PRV, porcine cytomegalovirus/roseolovirus; POD, postoperative day.

Figure 3

Postoperative courses of hyaluronan (a), heparan sulfate (b) and syndecan-1 (c) plasma concentrations. Group I, experiments deliberately terminated after 90 postoperative days with the baboons in excellent clinical condition, mean values ± SEM (n = 2); Group II, baboons with PCMV/PRV infections, mean values ± SEM (n = 2). PCMV/PRV, porcine cytomegalovirus/roseolovirus; POD, postoperative day.