Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine

A 12‐day course of high‐dose tacrolimus induces tolerance of major histocompatibility complex–mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart–lung cotransplantation using the same induction protocol. Hearts (n = 3), heart–kidneys (n = 3), lungs (n = 6), and hearts–lungs (n = 3) were transplanted into fully major histocompatibility complex–mismatched recipients treated with high‐dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart–kidney recipients and five of six lung recipients demonstrated long‐term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor‐specific unresponsiveness by cell‐mediated lympholysis/mixed‐lymphocyte reaction. In contrast, heart–lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.     

The Effects of Exogenous Administration of Human Coagulation Factors Following Pig‐to‐Baboon Liver Xenotransplantation

We sought to determine the effects of exogenous administration of human coagulation factors following pig‐to‐baboon liver xenotransplantation (LXT) using GalT‐KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large‐vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT.     

Access flow measurement by indicator dilution without indicator injection: effect of switch location

It is well known that the measurement of access flow by one of the various dilution techniques requires the reversal of blood flow drawn from and returned to the peripheral vascular access. But it was only recently recognized that the line switch itself constitutes a dilution experiment for certain blood and dialysate components and properties, so that a subsequent injection of indicator is no longer required. New switches introduced at different locations in the extracorporeal circulation not only simplify manual operation for standard access flow measurement but also provide an essential tool for the new technique, which is based on continuously measuring certain blood and/or dialysate characteristics and their changes caused by switching the bloodlines. In this study, the effects of switching the bloodlines at two different locations were studied when extracorporeal temperatures were used as a marker. The study shows that the temperature changes depend on the location of the switch relative to the extracorporeal temperature sensors, and that different algorithms to calculate access flow have to be used for the two possible switching positions to account for this dependence.