J Thorac Cardiovasc Surg 1994;107:624-0625
© 1994 Mosby, Inc.
Immunosuppressive treatment of venous allografts in dogs
F. Vermassen, MD,
A. Derom, MD,
H. Janzing, MD,
F. Derom, MD
Department of Experimental Surgery
Department of Vascular Surgery
University Hospital Ghent
De Pintelaan 185
9000 Ghent, Belgium
To the Editor:
Deaton and associates
1 reported their results with cryopreserved allograft venous conduits and the influence of immunosuppressive treatment with cyclosporine in dogs. They observed a reduction in cellular infiltrate in the animals treated with cyclosporine but no significant difference in patency in treated grafts.
We did comparable experiments in mongrel dogs to test different preservation protocols for venous allografts 2 and the influence of immunosuppressive treatment after implantation of a viable allograft. 3 A total of 230 arterial reconstructions, in which the ligated femoral arteries were bypassed with 6 cm segments of femoral vein, were performed in mongrel dogs. No aspirin was given after the operation. Extensive histologic and immunologic examinations (development of cytotoxic antibodies against donor lymphocytes) were performed. The dogs were followed-up for as long as 6 months.
Five different preservation protocols were compared. In each group, both autografts and allografts were implanted to discern the influence of the preservation method itself and the influence of the immunogenicity of the allograft. The groups tested were as follows: fresh veins, veins preserved in saline solution at 4° C for 1 month, veins preserved at -70° C for 1 month, veins preserved in 0.25% glutaraldehyde solution, and veins preserved in Hanks' solution with 15% dimethyl sulfoxide at -160° C for 1 month. The results were compared with those obtained after implantation of two types of synthetic graft (Figs. 1 and 2).
In the autografts, all fresh veins remained patent. Veins preserved in Hanks' solution with 15% dimethyl sulfoxide at -160 C, a method which has been shown to maintain the viability of the endothelial cells, 4 yielded comparable results. Veins preserved insaline solution at 4° C, -70° C and in glutaraldehyde solution gave results that were not better than those with synthetic grafts.
In the allografts, the results with fresh veins and veins preserved in Hanks' solution were significantly worse than with the corresponding groups of autologous veins. Histologic as well as immunologic evidence exists that rejection with damage to the endothelium was the mechanism responsible for these occlusions. In the other groups, no significant differences were found between autografts and allografts.
In a second set of experiments we therefore investigated whether immunosuppressive therapy could ameliorate the results obtained after implantation of a viable allograft. Cyclosporine at 4 mg/kg per day or prednisolone at 1 mg/kg per day was given during 1 month. Contrary to the observations of Deaton and associates, 1 we observed that cyclosporine but not prednisolone did indeed ameliorate significantly the results obtained with fresh and cryopreserved venous homografts, resulting in patency rates significantly better than those obtained in untreated dogs or with synthetic materials. Furthermore, most occlusions in the group with cyclosporine occurred after 1 month; a longer treatment might further ameliorate the results. Immunologic studies revealed that some antigenic matching between donor and host is advisable.
The difference between our results and those of Deaton and associates 1 may be due to the different immunosuppressive protocol and to the fact that in our study all implantations were performed by or under close supervision of the same surgeon. We conclude that homologous saphenous vein may be an acceptable substitute when an autogenous vein is not available at the condition of implanting a viable vein and (temporary) postoperative treatment of the host with cyclosporine. Storage in Hanks' solution with 15% dimethyl sulfoxide at -160° C can be used for the creation of vein banks, which offer the opportunity to have immunologically matched allografts available at any moment.
References
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Deaton DW, Stephens JK, Karp RB, et al. Evaluation of cryopreserved allograft venous conduits in dogs. J THORAC CARDIOVASC SURG 1992;103:153-62.[Abstract]
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Vermassen F, Degrieck N, De Kock L, Goubeau J, Van Landuyt K, Derom F. Venous allografts for vascular reconstructions. J Cardiovasc Surg 1992;33:641-9.[Medline]
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Vermassen F, Degrieck N, De Kock L, et al. Immunosuppressive treatment of venous allografts. Eur J Vasc Surg 1991;5:669-75.[Medline]
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Passani SL, Angelini GD, Breckenridge IM, Newby AC. Endothelial function can be preserved during cryo-storage of human saphenous veins. Eur J Cardiothorac Surg 1988;2:233-6.[Abstract]
