1992 Volume 6 Issue 5 Pages 555-561
An experimental study of the immunosuppressive effects of a new immunosuppressant, FK-506, in 23 canine lung allotranplantation is described. FK-506 was intramuscularly injected daily in a dose of 0.10 mg/kg after allotransplantation. One recipient dog died of lung rejection, but twenty two survived from 7 to 86 days until sacrifice. Microscopic examination showed a normal lung in 10, mild rejection in 8, moderate rejection in 2, and severe rejection in 3 dogs. No dog died of FK-506 toxicity, but 87% had appetite loss, 78% had diarrhea, and 9% had bloody stool during FK-506 treatment. Weight loss averaged 2.1 kg (18.9%) 3 weeks after transplant surgery. Mild rejection of the grafted lungs could not be detected on chest roentgenograms, but moderate rejection showed perihilar infiltration. Bronchofiberscopy showed no bronchial anastomotic stenosis, and the suture line was covered by normal mucosa 3 weeks after transplantaotion. The L/C ratio (bronchial mucosal blood flow at the second carina of the graft/blood flow at the carina of the recipient) was 1.05±0.24 (n=11) in normal lungs of control dogs. The L/C ratio decreased to 0.57 ± 0.09 (n=11) after transplantation, but recovered to 1.03 ± 0.10 (n=7) by 3 weeks after surgery. The inflammatory response score (IRS) was 8 (n=2), 4.3 ± 1.0 (n=4), and 2.0 ± 1.2 (n=7), 1, 2, and 3 weeks after transplantation, respectively. We have demonstrated that FK-506 is an effective immunosuppressant for canine lung allografts and that it does not interfere with the reconstruction of bronchial mucosal blood flow or the bronchial healing process. We conclude that FK-506 is a useful immunosuppressant for lung allotransplantation.
