New frontiers in heart transplantation. Clinical applications of basic research and new surgical approaches.
The growing understanding of alloimmune responses may help elucidate the mechanisms a novel immunomodulatory strategies, affording insights into new single or combination regimens. These insights are currently elusive because of the number of immuno-suppressive agents and techniques, the array of possible organ transplants, and the variety of experimental in vitro and in vivo models in diverse species. These possibilities add a bewildering level of complexity to the usual therapeutic problems of selecting drug doses, vehicles, routes, and schedules of administration. Although the results of in vitro assays have been used as indices of alloreactivity, they show only inconsistent correlations with clinical events. Only stringently controlled in vivo studies in rodents, large animals models, and humans will determine which agents or procedures represent real improvements over conventional therapy. The results of preclinical transplantation models and initial clinical trials suggest that immunosuppression for transplant patients is likely to evolve into various combination regimens. It appears now that there will be a choice between cyclosporine and FK506 as baseline immunosuppression because clinical experience has shown that these two drugs cause excessive nephrotoxicity when used in combination. Ideally the combination of additional new agents will enable the doses of cyclosporine and FK506 to be lowered to levels that are nonnephrotoxic and at the same time minimize or completely eliminate the need for corticosteroids and anti-T cell antibody therapy. The diverse mechanisms of immunosuppressive action of the new drugs under investigation certainly offer the hope for creative and effective strategies for the control of many forms of graft rejection in the near future.(ABSTRACT TRUNCATED AT 250 WORDS)
Costanzo
M R
MR
Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA.
Franco
K L
KL
D000818:Animals; D018014:Gene Transfer Techniques; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D006801:Humans; D007165:Immunosuppression Therapy; D009569:Nitric Oxide / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D009569:Nitric Oxide