IMMATURE HOST FOR XENOTRANSPLANTATION

The overall shortage of appropriate donor organs has prompted transpla nt physicians and surgeons to consider using organs from other nonhuma n species. The shortage of appropriate human donor hearts for newborn recipients is especially severe. Presently, the pig appears to be the most appropriate source for organs. Humans and baboons uniformly devel op high titers of complement-fixing (IgM) anti-pig xenoantibodies, res ulting in complement-mediated hyperacute rejection (HAR) of pig organs transplanted into mature baboons within minutes to hours. In contrast , newborn humans and baboons do not have high titers of anti-pig IgM x enoantibody, and consequently pig cardiac xenografts transplanted into newborn baboons do not undergo HAR Rather, these organs are rejected at days 3 to 4 by a distinctive immunologic process that involves natu ral killer cells and macrophages. With the addition of cyclosporine-ba sed triple immunosuppression, this process is reduced and graft life i s prolonged to 6 to 7 days. This therapy, however, is not sufficient t o prevent the induced humoral response to the graft, and the organs ar e rejected by antibody-and complement-dependent mechanisms. Future tre atment strategies to reduce this humoral response must incorporate imm unodepletion columns, soluble complement-inhibiting agents, and additi onal anti-B lymphocyte agents. These strategies, in conjunction with t he use of transgenic pig organs that express human membrane-bound comp lement regulatory proteins or reduced xenoantigenic epitopes could fur ther prolong graft life. Clinical trials are being formulated that wou ld utilize pig organs as a ''bridge,'' sustaining a newborn human in n eed of a heart transplant until an appropriate donor is located.