Canine vascularized allograft and autograft knee-joint transplants were studied in an attempt to develop a successful model that would obviate one of the major causes of bone-graft failure: delayed revascularization. Seventy animals with thirty-eight autografts (reimplantation) and thirty-two allografts (exchanges from one dog to another) were studied. Twenty-four animals with allografts were treated with a combination of antilymphocytic serum, azathioprine, and prednisolone. Each animal was studied clinically and by sequential roentgenograms and femoral arteriograms. Initial causes of failure in each group included: failed vascular anastomoses, necrosis of the muscles of the anterior compartment, loss of fixation, and infection. In each failure, the transplanted joint rapidly deteriorated and was clinically non-functional. Six autografts remained alive for longer than nine months; the longest period was 540 days. These grafted joints showed excellent function and were grossly and histologically well preserved when the animals were killed. In five of the twenty-four animals with allografts that were treated with the combined drugs the vascular anastomoses were open and the graft functioned for as long as one year, but the function of these grafts was not as good as that of the autografts. When the animals were killed these grafts were generally seen to be intact but they showed areas of cartilage loss and bone necrosis. No evidence of definitive immunological rejection could be identified. Our results indicated that if future experiments are to be successful, animals weighing more than eight kilograms should be used, and recent advanced microvascular techniques should be employed as well as rigid internal fixation of the osteotomies. In allografting, careful selection of each animal pair should be performed to avoid discrepancies in the sizes of both vessels and bones. * Read in part at the Annual Meeting of The American Academy of Orthopaedic Surgeons, Las Vegas, Nevada, February 5, 1973. t 2074 Abington Road, Cleveland, Ohio 44106. $ Dryburn Hospital, Durham DHI 5TW, England. 1 1380 Lusitana Street, Honolulu, Hawaii %813. CLIMCAL RELEVANCE: The failure of massive osteochondral grafts in tumor and trauma reconstruction is related to slow and incomplete revascularization. The identification of the conditions necessary for successful revascularization to proceed is of the utmost importance for an excellent clinical result. This study suggests an experimental model which could be useful in studying these conditions. Experimental transplantation of whole joints was initiated by Judet l7 in 1908. Clinical allotransplantation of whole joints was first performed and utilized by LexerZO, who reported a case in 1908. In his patient, a fresh cadaver tibia was used to replace the proximal part of a tibia which had been removed because of malignant tumor. The clinical results were reported to be satisfactory, and when the transplant was removed for religious reasons eighteen months later, the osteotomy site was well healed and the cmciate ligaments and cartilage were well preserved. Since then many studies, both experimental and clinical, have added to our knowledge of transplantation of parts of joints and of whole joints1~'.~.8-'0-'4.1~.24~26~30. These investigations have shown that when autografts are used, they function satisfactorily for a period of time but eventually deteriorate physically and biologically. It appeared from these studies that the major cause of failure was delayed revascularization with subsequent inadequate nutrition, collapse of the subchondral bone, and finally disintegration of the articular surfaces. Even when the bone components of the composite implant healed, the articular cartilage ultimately showed segmental replacement with a fibrous pannus. When allogeneic tissue was utilized, failure of the joint transplant was due to delayed revascularization and to immunological rejection, which played a major role. Bone and bone-marrow elements are strongly immunogenic, while cartilage appears to be only weakly ant igenic '~~. There is experimental evidence to show that immunological rejection of these components may be reduced either by drug immunosuppression of the host, utilizing agents such as aza th i~pr ine~ . '~ or antilymphocytic or by reducing the immunogenicity of the 414 THE JOURNAL OF BONE AND JOINT SURGERY TRANSPLANTATION OF THE CANINE KNEE JOINT 415 graft with chemical or physical methods13. Even when the antigenicity of a massive allograft is altered, there still is rapid deterioration of cartilage and eventual disintegration of the transplant. It appears, then, that in both massive autografts and allografts delayed revascularization is one of the major causes of failure. Studies by Judet and Padovani l 8 and by Reevesz5 showed the feasibility of experimentally transplanting whole joints on vascular pedicles to circumvent delayed revascularization as a cause of graft failure. With this background, we began to investigate a canine model of knee-joint transplantation of autografts (reimplantation) and of allografts (exchanged from one dog to another) in which immediate vascularity was supplied to the graft while appropriate immunosuppression was maintained. The purpose of this initial study was to determine the feasibility of this model and to identify and define the conditions necessary for a successful model. Once the factors for a successful vascular whole-joint transplant are defined, future studies will be able to provide additional data, such as the effects of immunosuppression on the animal, in a more controlled manner. Materials and Methods
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