Vascularized muscle allografts and the role of cyclosporine.
This study examined the fate of vascularized muscle allografts using a genetically defined rat model. Its purposes were (1) to analyze the histologic/immunologic responses, (2) to study the effect of cyclosporine on graft survival, and (3) to examine the possibility of inducing tolerance. In rats differing at a major histocompatibility locus, vascularized gastrocnemius muscle transplants were performed based on the sural branches of the femoral artery and vein. Forty-two animals studied were divided into three groups: Group 1, allografts, was treated without cyclosporine; Group 2, allografts, was administered continuous cyclosporine; and Group 3, allografts, was administered cyclosporine for 6 weeks only. Evaluation consisted of gross examination, H&E histology, and immunologic studies (MLC, CML, and complement-dependent 51Cr lysis assay). Lytic units (LU) were derived from the assays and served as the indicator of immune response. Group 1 animals had uniform rejection with intense cell-mediated response (LU 23 to 47) and low humoral response. Group 2 animals had viable allografts throughout with suppressed lytic unit values of 0 to 9 initially, which rose to 14 to 29 at 6 weeks despite continuous cyclosporine treatment. Group 3 animals showed rejection similar to the untreated animals. Autografts were performed as controls and survived indefinitely. Analysis of variance was significant at p less than 0.05. Using a reliable rat model for vascularized muscle allografts, we found that in transplantation across a major histocompatibility barrier, the initial immune response was primarily cell-mediated. Cyclosporine suppressed rejection only when given continuously, and short-term cyclosporine treatment did not induce a tolerant state. These data should be useful for future studies of vascularized muscle allografts.
Tan
C M
CM
Orthopedic Research Laboratory, Johns Hopkins Hospital, Baltimore, Md.
Yaremchuk
M J
MJ
Randolph
M A
MA
Lee
W P
WP
Burdick
J
J
Weiland
A J
AJ
D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage* / Q000494:pharmacology; D003601:Cytotoxicity Tests, Immunologic; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D006614:Hindlimb; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex; D009132:Muscles / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic
D003524:Cyclosporins