The Journal of Thoracic and Cardiovascular Surgery, Vol 105, 1-8, Copyright © 1993 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Prolonged lung allograft survival with a short course of FK 506
T Hirai, TK Waddell, JD Puskas, H Wada, S Hitomi, RM Gorczynski, AS Slutsky and GA Patterson
Department of Surgery, University of Toronto, Toronto General Hospital, Ontario, Canada.
We examined the hypothesis that FK 506 would induce graft acceptance after
lung transplantation. Left lung allotransplantation was performed in
size-matched mongrel dogs allocated to control (no immunosuppression, n =
3) and FK 506 (n = 5) groups. FK 506 (1.2 mg/kg intramuscularly every day)
was given on posttransplantation days 0, 1, and 2. No other
immunosuppressive agents were administered to either group. Chest x-ray and
transplant lung physiologic assessments were performed on the fifth day and
weekly thereafter. On day 29 an open lung biopsy and a third-party skin
graft were performed. Lymphocytes were harvested and frozen from the
recipient peripheral blood before transplantation and on days 8 and 29
afterwards for assessment in mixed lymphocyte reaction. Dogs were killed
when their chest x-ray films showed allograft opacification or when the
skin graft was rejected. Control lungs were all rejected after a median of
5 days. In the FK 506 group, one of five dogs aspirated during the
fifteenth-day assessment and was killed, on the twenty-ninth day, because
of severe rejection. At day 29, in the other four dogs, the transplanted
lung yielded an arterial oxygen tension of 613 +/- 25 mm Hg (mean +/-
standard deviation) and lung biopsy specimens showed no abnormalities
histologically. These four dogs rejected third-party skin grafts after a
median of 10 days. In two FK 506 dogs, mixed lymphocyte reaction at day 8
showed suppression of proliferation responses against donor and third-party
lymphocytes. By day 29 responses against third-party lymphocytes had
returned to almost preoperative levels, whereas antidonor responses were
still suppressed. After skin graft rejection and killing, one of four dogs
showed no sign of rejection, and the other three showed minimal to mild
lung rejection at the time they were killed. We conclude that a 3-day
course of 1.2 mg/kg of FK 506 induced prolonged graft acceptance after lung
transplantation in dogs.
