The inability to reconstruct extensive and often life-threatening tracheal defects is a clinical dilemma. The objective of this study was to achieve microvascular revascularization and transplantation of long-segment circumferential tracheal allografts in a canine model. Fifteen mongrel dogs were randomly assigned to 5 treatment groups. Twelve dogs underwent an excision of an 8-cm tracheal segment followed by transplantation and microvascular revascularization of an 8-cm cervical trachea allograft. Group 1 (n = 4) was treated with 10 mg/kg per day of cyclosporin A (CsA) and 7.5 mg/kg per day of mycophenolate mofetil (MM). Group 2 (n = 4) was treated with 5 mg/kg per day of CsA and 7.5 mg/kg per day of MM. Group 3 (n = 4) was treated with 2.5 mg/kg per day of CsA and 7.5 mg/kg per day of MM. Group 4 (n = 2) underwent an autograft tracheal transplant and received postoperative 2.5 mg/kg per day of CsA and 7.5 mg/kg per day of MM. Group 5 (n = 1) did not undergo surgery, but received postoperative 2.5 mg/kg per day of CsA and 7.5 mg/kg per day of MM. The animals were maintained for a duration of 30 days, during which time the graft was assessed by routine endoscopic examination and tracheal biopsies. Ex vivo, tracheal autografts were examined grossly for graft healing and microscopically for histologic architecture. The mean survival times were 13.25 days (group 1), 16 days (group 2), and 20 days (group 3). There was 1 early allograft failure secondary to microvascular thrombosis, and there were 4 delayed failures secondary to postoperative wound infections. Five dogs were euthanized before the end of the 30-day observation period because of failure to thrive or hypocalcemic tetany. None of the dogs in the study demonstrated endoscopic or histologic evidence of rejection before euthanasia. Postmortem examination of the surviving dogs demonstrated normal histologic architecture without evidence of rejection. For the first time, we have achieved allotransplantation of long tracheal segments based on the cranial thyroid artery and internal jugular vein. Minimal systemic immunosuppression appears to be associated with a higher survival rate and a lower complication rate.
Development of alternative gene transfer techniques for ex vivo and in vivo gene therapy in a canine model