Experimental tracheal allograft revascularization and transplantation

Abstract

The feasibility of tracheal allotransplantation with a fascial vascular carrier was examined in three groups with varied dose sequences of immunosuppression. A control group (group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 5 mg/kg (group 2), 5 mg/kg plus 3 mg/kg methylprednisolone (Solu-Medrol) (group 3), and 10 mg/kg (group 4) for 6 weeks or until death. Grafts were assessed by silicone dye infusion of the artery of the fascial flap to examine their microcirculation and by quantitative histologic study. Group 1 evidenced complete rejection after a heterotopic revascularization period of 14 days. The allografts of the experimental groups remained viable after 14 days of revascularization and could be transplanted orthotopically after this period. After transplantation, the viability of group 2 tracheas was unpredictable with changes ranging from mild to complete rejection. Group 3 evidenced well-preserved transplant viability with infection-induced necrosis at the anastomoses caused by the corticosteroid component. All group 4 animals survived the follow-up period with normal allograft viability. Cyclosporine in a dosage of 10 mg/kg per day can effectively suppress the immune response after transplantation of vascularized tracheal allografts. This experimental model will allow future studies to examine airway wall immunogenicity.

Learning Curve in Tracheal Allotransplantation

“…Triple immunosuppression therapy was started intravenously and maintained orally. (1). The membranous trachea was removed and the cartilaginous trachea was placed over the dissected recipient fascia and wrapped with this fascia (arrows-2).…”

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“…In 1994, a 2-stage tracheal transplant was described in rabbits using a fascial flap. 5,15 The tracheal graft was implanted heterotopically into the lateral thoracic fascia for revascularization, and the graft was orthotopically transplanted into the trachea; the results were successful, and the optimal time for the second stage was 2 to 3 weeks after the first stage. 5,15 However, this technique was not applied to humans.…”

“…Clinical and experimental studies have suggested that tracheal allograft is a curative option for treating long-segment tracheal defects. [4][5][6] However, the tracheal allograft lacks an identifiable vascular pedicle that would allow direct vascular anastomosis to the blood vessels in the recipient's neck. Therefore, the safe restoration of the blood supply of the graft is a key factor to achieve successful outcomes of tracheal anastomoses.…”

Head and Neck Reconstructive Surgery

“…Indirect revascularization of a donor trachea is perfectly feasible, as demonstrated by the successful outcome of tracheal allografts and of autografts using vascularized fascia flaps in laboratory animals and humans (Buckwalter, 1998, Delaere et al, 1995. When this recipient tissue is perfused by an identifiable vascular pedicle, a microvascular transfer can be performed after the prefabrication step ).…”