In the absence of artificial organ

support, failure of the hepatic graft to promptly function would be tantamount to death. Finally, how could immediately life-supporting deceased donor livers be obtained in an era in which death was defined as the cessation of heartbeat and respiration? These questions and issues mandated consideration of the less draconian auxiliary hepatic transplant operation of Welch that might allow recipient survival, even if the graft failed. This option was undermined when the rapid atrophy of auxiliary livers that previously had been ascribed to rejection in unmodified dogs,86,113 was shown to be equally severe in animals in which rejection was prevented with azathioprine.11 The die was cast for the liver replacement (orthotopic) option. Liver replacement was carried out in seven deceased donor liver recipients between March 1963 and January 1964: click here five in Denver (cases 1-4 and 6), one in Boston (case 5 by Moore’s team), and one in Paris (case 7) (Table 3).10,

1188,114 All seven patients died, two during the operation and the other five after 6.5-23 days. Neither primary nonfunction nor uncontrolled rejection of the grafts were lethal factors in any Ivacaftor cell line of the failures. At autopsy of the four Denver patients who survived the operation, pulmonary emboli were found that apparently had originated in the bypass tubing used to decompress the blocked systemic and splanchnic venous beds during the removal and replacement of the native liver. Ironically, the bypass which had been an essential component of the canine operation, is not mandatory in most human recipients, or even in dogs if venous collateralization is

encouraged by bile duct ligation a month in advance.115 By the time our fourth and fifth liver recipients were selleckchem reported to the American Surgical Association in April 1964,11 all clinical liver transplant activity had ceased in what would be a voluntary 3.5-year worldwide moratorium. The self-imposed decision to stop did little to quiet polite but unmistakably disapproving discussions of an operation that had come to be perceived as too difficult to ever be tried again. In effect, it now would be necessary to return to ground zero and reexamine all five of the themes of Table 1. The central assumption of Theme I had been that portal venous blood contained hepatotrophic molecules. The hypothesis was consistent with our results in 1958-1960 in nonimmunosuppressed canine recipients of replacement livers,3 and especially with the acute atrophy of Welch’s auxiliary grafts in azathioprine-treated dogs (see above, and Starzl et al.11). The possibility was now explored of providing the auxiliary allografts with direct access to the portal molecules.116 But what were the hepatotrophic factors? Using double liver fragment nontransplant models derived from Welch’s auxiliary liver operation (Fig.