J Thorac Cardiovasc Surg 2004;127:1850-1851
© 2004 The American Association for Thoracic Surgery
Pathology of fresh versus cryopreserved homograft heart valves
Jean Francois Légaré, MD
Dalhousie University, Halifax, Nova Scotia, Canada
David B. Ross, MD
University of Alberta, Edmonton, Alberta, Canada
To the Editor:
In "The Pathology of Fresh and Cryopreserved Homograft Heart Valves: An Analysis of Forty Explanted Homograft Valves," Koolbergen and colleagues1 attempted nicely to reconstruct the sequence of events leading to failure of homografts from a data set of 40 explanted valves examined histologically. Despite the limitations of such a study and the significant variability among patients, they convincingly observed a reduction in valve leaflet cellularity that appears to occur within the first year after implantation.
The loss of cellular elements has also been previously reported by others, but what remains unclear is the exact cause for this loss of donor cells.2,3 Although it is clear is that some immune cell infiltration can be demonstrated, as well as evidence of donor-specific immune activation, a direct causal relationship remains difficult to prove. In this article Koolbergen and colleagues1 described some early infiltration of immune effector cells, such as macrophages and T lymphocytes. This observation may in fact represent evidence of immune-related valve injury, despite the absence of up-regulation of cell adhesion molecules, because the timing for up-regulation of cell adhesion molecules may be quite difficult to detect and impossible to evaluate with certainty in this type of analysis.
What is particularly interesting about this loss of cellular elements is that similar findings have been duplicated in a rat model of allograft failure, in which valve leaflet cellularity was demonstrated to be significantly reduced with time.4 In this rat model immune-specific cells (T lymphocytes) were recruited in allografts, resulting in apoptotic cell death of donor cellular elements.4 The entire process was absent in syngeneic valves and could be inhibited by T-cell immunosuppression and cell adhesion molecule blockade, suggesting that allograft valve failure is at least in part immune mediated.4,5 Most of the evidence for immune-mediated damage in this model occurred in the first 2 weeks after implantation, and by 4 weeks the valves were largely acellular. It is not surprising then that Koolbergen and colleagues1 could find little evidence of immune-mediated injury—despite showing, in the valve explanted at 2 weeks, an obvious T-cell infiltrate. Any such injury almost certainly had to have occurred before the majority of these valves were explanted (median 4 years).
The contribution of cellular elements to the homograft survival appears poor, as suggested by their significant disappearance early after implantation. Taken together, a homograft with less viable cellular elements and well-preserved ultrastructure may be ideal in provoking the least donor-specific immune response and therefore contributing to limited valve injury after implantation. This finding supports current efforts to create a cell-free or nonimmunogenic homograft for clinical use.6
 |
References
|
|---|
- Koolbergen DR, Hazekamp MG, de Heer E, Bruggemans EF, Huysmans HA, Dion RA, et al. The pathology of fresh and cryopreserved homograft heart valves: An analysis of forty explanted homograft valves. J Thorac Cardiovasc Surg. 2002;124:689–697[Abstract/Free Full Text]
- Mitchell RN, Jonas RA, Schoen FJ. Pathology of explanted cryopreserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg. 1998;115:118–128[Abstract/Free Full Text]
- Mitchell RN, Jonas RA, Schoen FJ. Structure-function correlations in cryopreserved allograft cardiac valves. Ann Thorac Surg. 1995;60(2 Suppl):S108–S113[Medline]
- Légaré JF, Ross DB, Issekutz TB, Ruigrok W, Creaser K, Hirsch GM, et al. Prevention of allograft heart valve failure in a rat model. J Thorac Cardiovasc Surg. 2001;122:310–317[Abstract/Free Full Text]
- Légaré JF, Lee TD, Creaser K, Ross DB. T lymphocytes mediate leaflet destruction and allograft aortic valve failure in rats. Ann Thorac Surg. 2000;70:1238–1245[Abstract/Free Full Text]
- Cebotari S, Mertsching H, Kallenbach K, Kostin S, Repin O, Batrinac A, et al. Construction of autologous human heart valves based on an acellular allograft matrix. Circulation. 2002;106(12 Suppl 1):I63–I68[Medline]
Top
References