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J Thorac Cardiovasc Surg 1999;117:1044-1045
© 1999 Mosby, Inc.

LETTERS TO THE EDITOR

David B. Ross, MD, Gillian R. Hamilton, BA, James R. Wright, Jr, MD, PhD, Timothy D. G. Lee, PhD

Division of Cardiovascular Surgery
IWK Grace Hospital for Children
PO Box 3070
Halifax, Nova Scotia, Canada B3J 3G9

Homograft valve failure in children

To the Editor:

We read with interest the article by Rajani, Mee, and Ratliff. ¹ Their finding of a lymphocytic infiltrate associated with rapid failure of cryopreserved homografts in infants lends support to the hypothesis of an immunologic injury being at least partially responsible for this failure. This concurs with our own clinical ² and laboratory ³ findings but is not supported by others. ⁴

Rajani, Mee, and Ratliff end their article with speculation about the possible use of tissue matching and immunosuppression in these patients. Although we believe that there is evidence for an immunologic component to this accelerated failure, we would caution against the empiric use of immunosuppression in these children without further controlled studies. In a small pilot study we transplanted cryopreserved aortic valve grafts into 21 outbred rats as previously described ³ and randomly assigned 11 to receive oral cyclosporine (10 mg/kg per day) (INN: ciclosporin) for 56 days while the remaining 10 received a placebo. The striking finding of this study was that only 3 of the 11 grafts in the cyclosporine-treated group remained patent at 8 weeks whereas 8 of 10 in the placebo group were patent (P = .03, Fisher's exact test). The patent cyclosporine grafts did have less medial necrosis and perivascular inflammation than control grafts. The cause of this high occlusion rate in the cyclosporine-treated group is unknown but may be due to a direct toxic effect of cyclosporine on the endothelium of these small grafts. ⁵ Whether the same effect would occur in larger grafts is unknown.

It is likely that these avascular cryopreserved grafts fail by mechanisms of rejection that are substantially different from those affecting vascularized whole organs. Thus directly transferring immunosuppressive regimens used successfully for cardiac or renal transplantation may not be appropriate. We postulate that there is an immune-mediated attack on these grafts that damages their structural elements, making them more susceptible to early degeneration. Much more work is required to determine if this indeed is the case and to determine how best to minimize this response. We do not believe that sufficient data are yet available to recommend immunosuppression in children requiring homograft valves.

12/8/96855

[Response declined]

References

1. Rajani B, Mee RB, Ratliff NB. Evidence for rejection of homograft cardiac valves in infants. J Thorac Cardiovasc Surg 1998;115:111-7. [Abstract/Free Full Text]
   
2. Baskett RJ, Ross DB, Nanton MA, Murphy DA. Factors in the early failure of cryopreserved homograft pulmonary valves in children: Preserved immunogenicity? J Thorac Cardiovasc Surg 1996;112:1170-9. [Abstract/Free Full Text]
   
3. Moustapha A, Ross DB, Bittira B, et al. Aortic valve grafts in the rat: Evidence for rejection. J Thorac Cardiovasc Surg 1997;114:891-902. [Abstract/Free Full Text]
   
4. Mitchell RN, Jonas RA, Schoen FJ. Pathology of cryopreserved allograft heart valves: Comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg 1998;115:118-27. [Abstract/Free Full Text]
   
5. MacDonald AS, Sabr K, MacAuley MA, McAlister VC, Bitter-Suermann H, Lee T. Effects of leflunomide and cyclosporine on aortic allograft chronic rejection in the rat. Transplant Proc 1994;26:3244-5. [Medline]
   

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This Article Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David B. Ross James R. Wright, Jr Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ross, D. B. Articles by Lee, T. D. G. Search for Related Content PubMed PubMed Citation Articles by Ross, D. B. Articles by Lee, T. D. G.