Obliterative airway disease and graft stenting in pig-to-dog tracheal xenotransplantation

Abstract

Obliterative airway disease occurring in concordant tracheal xenografts in rodent models is histologically similar to obliterative bronchiolitis in human lung allografts. We studied whether obliterative airway disease would occur in a large animal-discordant model. Pig and dog tracheas were cryopreserved for 7 to 14 days, and 18 recipient dogs given splenectomy 7 days before transplantation, then seven tracheal rings were removed and a corresponding five-ring donor tracheal segment was transplanted to the excised site. Grafts were wrapped with pedicled omentum and inmmunosuppression was conducted with tacrolimus or deoxyspergualin. Graft status was observed by bronchoscopy. Dogs were classified into three groups. Group 1 consisted of dog-to-dog allotransplantation animals (control group, n = 5), Group 2 of pig-to-dog xenotransplantation animals (n = 8), and Group 3 of pig-dog xenotransplantation animals who also underwent graft stenting immediately after transplantation (n = 5). Grafts healed well in 4 of 5 Group 1 dogs. Tracheal stricture began on day 5 post transplantation and the lumen was obstructed by fibrosis by days 8 to 14 in all Group 2 dogs. All Group 3 dogs remained in good respiratory status until death. Obliterative airway disease developed quickly in pig-to-dog discordant tracheal xenografts. Graft stenting is a feasible treatment for managing of tracheal obstruction.