The influence of the rapamycin-derivate SDZ RAD on the healing of airway anastomoses.
OBJECTIVE
Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses.


METHODS
The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n=4) were without, and study animals (group 2, n=6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured.


RESULTS
All animals survived without complications. Serum levels of SDZ RAD were 30.9+/-8.7 ng/ml (recommended level 20-40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75+/-0.35 vs. 7.69+/-1.39 N, P=0.01). Histology did not show a significant change in histoarchitecture between the groups.


CONCLUSIONS
Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients.
Dutly
André E
AE
Division of Thoracic Surgery, University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Gaspert
Ariana
A
Inci
Ilhan
I
Schneiter
Didier
D
Korom
Stephan
S
Weder
Walter
W
D000714:Anastomosis, Surgical; D000818:Animals; D001696:Biomechanical Phenomena; D000068338:Everolimus; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation; D023421:Models, Animal; D020556:Neutrophil Infiltration; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013552:Swine; D014132:Trachea / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D014945:Wound Healing / Q000187:drug effects*
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus