Improved hepatic microcirculation by human soluble urinary thrombomodulin in the xeno-perfused porcine liver

Purpose. Both the protein C/thrombomodulin system and the heparin/anti-thro mbin III system are major physiological anticoagulant systems, which may al so play a major role in preserving the hepatic microcirculation in xenogene ic liver transplantation. To compensate for the functional incompatibilitie s of the porcine thrombomodulin (TM)-cofactor activity beyond species for h uman thrombin, soluble human TM protein was tested in xenogeneic perfusion of the porcine liver, Materials and Methods. The livers were harvested from adult female pigs and perfused through the portal vein (PV) and hepatic artery (HA) for 2 hr, wi th fresh human blood in group 1 (n=5), fresh porcine blood (10 units/ml) in group 2 (n=5), and fresh human blood with TM (50,000 units/1.5 l) in group 3 (n=5), The tissue PO, level, tissue blood flow, PV and HA pressures were all continuously monitored. Circulating perfusate and liver tissue samples were periodically obtained for blood chemistry and histologic analyses. Results. The activated protein C (aPC) level was significantly elevated in the TM-treated group 3. (47.5%+/-3.5% at preperfusion and 51%+/-2.8% after 120 min of perfusion) in comparison to group 1 (32.3%+/-7.2% and 35.3 +/- 1 2.0%). The hepatocyte enzyme release of aspartate aminotransferase (AST) wa s sup pressed significantly more in group 3 (238.2 +/- 107 IU/l), than in g roup 1 (672.3 +/- 160 IU/I) at 2 hr after reperfusion, In group 3, the tiss ue PO, levels and tissue blood flow also remained significantly higher thro ughout the perfusion. The platelet counts in the perfusate remained signifi cantly higher in group 3 (37.1% to 74.3% of the preperfusion level) than in group 1 (4.4% to 14.7%), after 0 to 80 min of perfusion. According to the histologic findings, the degree of interlobular hemorrhaging and congestion decreased remarkably more in group 3 than in group 1, Conclusion, These findings thus indicated that soluble thrombomodulin prote in extracted from human urine remarkably improved hepatic microcirculation in the xenoperfused porcine liver. The thrombomodulin/protein C system migh t, thus, play an important role in restoring the physiological anticoagulan t system in the xenoperfused porcine liver.