Ann Thorac Surg 2002;74:1271-1275
© 2002 The Society of Thoracic Surgeons
Review
Immunology and failure of valved allografts in children
Robert E. Shaddy, MDa*,
John A. Hawkins, MDb
a Department of Pediatrics University of Utah School of Medicine and Primary Children’s Medical Center, Salt Lake City, Utah, USA
b Department of Surgery, University of Utah School of Medicine and Primary Children’s Medical Center, Salt Lake City, Utah, USA
* Address reprint requests to Dr Shaddy, Division of Pediatric Cardiology, Primary Children’s Medical Center, 100 North Medical Dr, Suite 1500, Salt Lake City, UT84113, USA.
e-mail: pcrshadd{at}ihc.com
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Abstract
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Valved allografts are frequently used in the repair of congenital heart defects in children. Although the longevity of these grafts is generally very good, there continue to be ongoing problems with allograft stenosis, allograft valve insufficiency, and subsequent allograft failure, particularly in younger children. This review presents data on the immunologic and nonimmunologic risk factors implicated in valved allograft failure, in addition to ongoing investigation into the improvement of allograft function.
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Introduction
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It has been recognized for some time now that cryopreserved allografts demonstrate accelerated degeneration and need for reoperation in children, particularly young infants, as compared to those for adult patients. Investigators have put forth many possible etiologies for this phenomenon of accelerated valved allograft failure in children. Risk factors for allograft degeneration are younger recipient or donor age, longer donor ischemic times, significant allograft size mismatch (donor size less than two standard deviations below recipient size), aortic rather than pulmonary valved allograft type, and the use of Dacron (C. R. Bard, Murray Hill, NJ) conduit extension [1–4]. In broad terms, allograft degeneration may be due to factors related to, or unrelated to, immunologic injury.
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Nonimmunologic factors
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Factors unrelated to immunologic injury would include mechanical factors, such as sternal compression, or oversizing or undersizing of conduits with anatomic distortion, in addition to ischemic injury. Ischemic injury to the valved allograft may play a significant role in allograft dysfunction. Rat aortic isografts (same strain, and thus immunologically neutral) have been shown to demonstrate low-grade intimal thickening after implantation, suggesting a proliferative response to ischemic injury [5, 6]. Similarly, cryopreserved (but not fresh) rat aortic valve isografts show moderate and diffuse neointimal proliferation after implantation [7]. What is clear is that the obligatory ischemic period prior to cryopreservation plays a definite role in the viability of cells in heart valve preparations and may play a role in the long-term durability depending on the structural integrity of the graft [8].
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Immunologic factors
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Factors related to immunologic injury include ABO incompatibility and human leukocyte antigens (HLA) incompatibility. The role of tissue processing and cryopreservation in the immunogenicity of valved allografts has been a subject of debate since the first reports of the use of these grafts [9]. Tissue processing steps such as warm ischemic time, antibiotic disinfection, cryopreservation, and thawing all affect viability of the grafts [10, 11]. Although the importance of viability is debated, more viable allografts may function better, although they also may be more immunologically reactive [12]. Antibiotic preservation may also reduce the immunostimulatory potential of valved allografts [13]. Although some have argued that cryopreservation may actually reduce the immunologic reactivity of valved allografts [14], others have argued that the converse may be true [9, 15]. Clearly, cryopreservation results in preservation of some endothelial cells [16] and perhaps more fibroblasts [17], as indicated by the capacity for procollagen synthesis following implantation [18] and the persistence of donor-derived viable cells in explanted allografts [19]. Some investigators have failed to demonstrate any evidence of a cellular infiltration in explanted valved allografts. These studies describe explanted valved allografts as having minimal, if any, viable cells but retain the original collagen network [20, 21]. More recently, investigators have demonstrated significant cellular infiltration with T-cells and B-cells in failed explanted valved allografts in children [22, 23]. Evidence for immune injury as a mechanism for valved allograft degeneration comes from studies in cell culture, animals, and humans. Canine venous allografts will thrombose unless treated with immunosuppression [24]. Similarly, after implantation, rat aortic allografts demonstrate massive cellular infiltration, intimal thickening, and medial necrosis, in addition to marked thickening of the valve wall and leaflet. This response appears to be T-cell mediated in the rat and leads to leaflet destruction [25]. These changes are not seen with rat isografts or autografts [5–7].
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Younger age
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Hawkins and coworkers described the increased risk of degeneration of valved allografts placed between the right ventricle and pulmonary arteries in infants when compared with older children [26]. In their study, children older than 1 year of age had a 94% freedom from death or valve explantation at 3 years after surgery compared with 50% in children younger than 1 year of age. Two subsequent reports have also shown a similar phenomenon in which they described an increased risk of degeneration of aortic valve allografts in smaller children when compared with older children [27, 28]. In these studies, small children had an 85% to 88% freedom from death, or valve dysfunction or explantation, at 3 years after surgery compared with 42% to 53% in older children. These investigators also demonstrated an increased risk of valve dysfunction from aortic allografts when compared to pulmonary allografts, although data on this is somewhat conflicting.
The reason for the increased valved allograft dysfunction in the young is unknown. Although it has been speculated that young children may demonstrate a more vigorous immune response, this is not supported by studies looking at humoral and T-cell responses to valved allografts in children [29, 30]. It stands to reason that perhaps smaller donor and recipient size could contribute to increased valve dysfunction solely on the basis of different growth rates between smaller and larger allografts. However, Tweddell and coworkers have argued against this by showing that the net change in allograft Z-value from implantation to last follow-up was not significantly different between a group of patients with allograft failure or dysfunction and a group of patients without allograft failure or dysfunction [2].
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ABO incompatibility
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When trying to narrow down the cause of the immunologic reaction, both ABO incompatibility and HLA incompatibility have been examined. The effect of ABO incompatibility on valved allograft longevity is unclear. Shaddy and coworkers retrospectively analyzed valved allograft function in 39 children who received valved allografts as part of the repair of a congenital heart defect [31]. They found that ABO incompatibility was not associated with an increased incidence of valve insufficiency or calcification. However, aortic allografts did calcify more than pulmonary allografts. The lack of an effect of ABO incompatibility was confirmed recently by Kadner and associates in which they showed that while ABO antigens are well expressed on the endothelium of fresh valves, cryopreserved valves did not express carbohydrate antigen and thusly ABO blood group incompatibility does not appear to play a significant role in allograft valve degeneration [32]. Others, however have demonstrated a greater incidence of immunologic reaction with ABO incompatible cryopreserved valved allografts [33].
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HLA incompatibility
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The effects of HLA incompatibility have recently become an area of intense research. In cell culture, fresh and cryopreserved valve pieces or allograft endothelial cells are capable of stimulating immunocompetent cells, a property that is reduced by cryopreservation or HLA-DR matching [34–36]. Rats who receive an aortic valve allograft demonstrate a donor-specific T-cell and antibody-mediated response [37], and dogs have also been shown to mount a donor-specific antibody response against major histocompatibility complex antigens on fresh venous allografts [38].
Perhaps the first report of HLA antibodies in humans after valved allograft implantation was by Smith and coworkers [39]. In a retrospective analysis of 73 adults who had previously undergone valved allograft implantation, they showed that valved allografts stimulate a strong HLA-specific antibody response that can persist for up to 15 years. Soon after this, Shaddy and coworkers reported a prospective analysis of the HLA antibody response to valved allograft implantation in children [29]. This study was prompted by the anecdotal finding of markedly elevated HLA panel reactive antibodies (PRA) in 2 infants who had previously undergone placement of allograft tissue as part of their reparative surgery for a congenital heart lesion. In their prospective study, the investigators compared circulating HLA antibodies (PRA) in 9 children who underwent open heart surgery for repair of a congenital heart defect who required placement of a valved allograft to 11 children of similar age who underwent repair of a congenital heart defect without placement of any allograft tissue. PRA was measured before surgery, and 1 week, 1 month, and 3 months after surgery. In this study, the PRA was measured to quantitate the circulating HLA antibodies using the antiglobulin cytotoxicity technique. The authors found that children who received a valved allograft demonstrated a marked increase in PRA from 3.2% before surgery to 99.7% 3 months after surgery. In contrast, patients who received no allograft demonstrated no circulating HLA antibodies (Fig 1). These antibodies persist for at least 1 year after implantation [40]. Subsequently, other authors have demonstrated HLA antibodies against both class I and class II antigens in adults and children who have received valved allografts at the time of surgery [41]. These studies clearly demonstrate that adults and children mount a vigorous HLA antibody response to implantation of a valved allograft. Although valved allografts induce an immune response, it is unclear whether this is due to valve tissue, or vascular tissue, or both. A recent prospective analysis of children receiving nonvalved allograft tissue at the time of surgical repair of a congenital heart defect has demonstrated that nonvalved allograft tissue also elicits a vigorous antibody response against both class I and class II HLA antigens [42]. Others have subsequently reported, prospectively, the presence of HLA class I and class II antibodies in adults and children after implantation of cardiac valved allografts [41, 43]. In addition to this antibody response, investigators have recently demonstrated the presence of circulating donor-specific cytotoxic T-lymphocytes and helper T-lymphocytes in children and adults after valved conduit implantation [30, 44]. The authors speculate that this may reflect an ongoing process of cell-mediated destruction of the valved allograft tissue which may contribute to graft failure.
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Fig 1. Panel reactive antibodies in allograft patients (patients receiving an allograft) and control patients (patients not receiving an allograft) before, 1 mo after, and 3 mo after surgery. *Indicatesp < 0.01 compared with control patients and compared with allograft patients before surgery.
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The consequences of this immune response to allograft tissue implantation are unclear. Although some patients appear to have a significant problem with allograft dysfunction, others do not. It is tempting to speculate that a vigorous immune reaction to allograft tissue can result in allograft damage manifested as luminal stenosis, valve dysfunction (both stenosis and regurgitation), and calcification. There is recent evidence in rats that the consequences of this donor-reactive immune response result in early allograft destruction and incompetence [45]. Furthermore, immunomodulatory approaches (cyclosporine and anti-
4/ß2 integrin treatment decreases allograft damage [46, 47]. In humans, studies have failed yet to demonstrate a correlation between HLA antibodies and echocardiographic abnormalities in valved allograft function [48]. In our experience, there has been very little variability in the vigorous HLA antibody response to valved and nonvalved allografts [29, 42]. Thus, the variability in allograft function over time after allograft implantation may be due to both immunologic and nonimmunologic factors. In addition to concerns about immunologic allograft damage from allograft implantation, there are potential deleterious consequences of circulating HLA antibodies in selected patients. For instance, a small number of these patients who receive valved allografts at the time of surgery go on to require heart transplantation. In these patients, circulating HLA antibodies could significantly complicate transplantation, in some cases limiting the donor pool because of the need for prospective crossmatching.
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Possible methods to reduce the immune response
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If one accepts the fact that this immune response is undesirable, then there are at least three possible solutions to alleviate this response. One would be to match all allografts by blood type and HLA type. However, this is unrealistic because of the limited number of allograft donors. Another would be to somehow remove the immunogenicity of valved allograft tissue, perhaps by removing the antigen presenting cells on the allograft. This is an area of intense research and current studies are underway with these types of decellularized valves [49]. The preliminary results of these valves is encouraging with virtually all patients with preoperative negative HLA antibodies remaining with PRA levels less than 10% at 1 and 3 months postoperatively [49]. The remaining question is whether the lack of an immune response with these new decellularized valves will translate into improved durability and function. Another approach has been the development of tissue-engineered valves in which a biodegradable matrix and autologous cells are used to "grow" a tissue-engineered valve that has shown some promise with ability to remodel in the animal model [50]. The third option would be to immunosuppress the recipient in order to abrogate the immune response of the recipient to the donor allograft. Previous studies in animals have demonstrated that immunosuppression with cyclosporine or mycophenolate mofetil may reduce the alloimmune response to arterial and venous allograft implantation in rats and dogs [24, 51, 52]. However, a prospective randomized trial of azathioprine in children receiving valved allografts at surgery failed to demonstrate any reduction in the antibody response to allograft implantation [53]. Although it is likely that this immune response could be blocked with higher levels of immunosuppression as is used in solid organ transplantation, the significant risks associated with such intense immunosuppression may not be warranted. Further studies will be necessary to determine the importance of the immune response to valved allografts and the best way to get around this problem.
In conclusion, the function and longevity of valved allografts implanted into children for the treatment of congenital heart lesions are not ideal. The roles of immunologic and nonimmunologic factors are currently being elucidated and both factors are important. There is good evidence now that valved and nonvalved allograft tissue induces a significant HLA antibody response in children who receive these grafts. Although the consequences of this response are still unclear, ongoing investigation into these consequences and into methods of safely reducing this immune response are warranted. Better methods of defining immunologic and nonimmunologic risk factors in allograft implantation and implementing strategies to reduce morbidity from these factors will improve both the function and longevity of these tissue allografts.
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References
|
|---|
- Baskett R.J., Ross D.B., Nanton M.A., Murphy D.A. Factors in the early failure of cryopreserved homograft pulmonary valves in children: preserved immunogenicity?. J Thorac Cardiovasc Surg 1996;112:1170-1179.[Abstract/Free Full Text]
- Tweddell J.S., Pelech A.N., Frommelt P.C., et al. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation 2000;102(Suppl 3):III130.
- Niwaya K., Knott-Craig C.J., Lane M.M., et al. Cryopreserved homograft valves in the pulmonary position: risk analysis for intermediate-term failure. J Thorac Cardiovasc Surg 1999;117:141-147.[Abstract/Free Full Text]
- Bull C., Macartney F.J., Horvath P., et al. Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits. J Thorac Cardiovasc Surg 1987;94:12-19.[Abstract]
- Motomura N., Imakita M., Yutani C., et al. Histological change in cryopreserved rat aortic allograft. J Cardiovasc Surg (Torino) 1995;36:53-60.[Medline]
- Green M.K., Walsh M.D., Dare A., et al. Histologic and immunohistochemical responses after aortic valve allografts in the rat. Ann Thorac Surg 1998;66(Suppl):S216.
- Moustapha A., Ross D.B., 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]
- Crescenzo D.G., Hilbert S.L., Barrick M.K., et al. Donor heart valves: electron microscopic and morphometric assessment of cellular injury induced by warm ischemia. J Thorac Cardiovasc Surg 1992;103:253-258.[Abstract]
- Ross D.N. Evolution of the homograft valve. Ann Thorac Surg 1995;59:565-567.[Free Full Text]
- McNally R.T., Brockbank K.G. The correlation between improved cellular viability and clinical performance in 5,000 cryopreserved human heart valves. ASAIO Trans 1991;37:M355-356.[Medline]
- Niwaya K., Sakaguchi H., Kawachi K., Kitamura S. Effect of warm ischemia and cryopreservation on cell viability of human allograft valves. Ann Thorac Surg 1995;60(Suppl):S114.
- Gall K.L., Smith S.E., Willmette C.A., O’Brien M.F. Allograft heart valve viability and valve-processing variables. Ann Thorac Surg 1998;65:1032-1038.[Abstract/Free Full Text]
- Johnson D.L., Sloan C., O’Halloran A., Yacoub M.H. Effect of antibiotic pretreatment on immunogenicity of human heart valves and component cells. Ann Thorac Surg 1998;66(Suppl):S221.
- Motomura N., Imakita M., Yutani C., et al. Histologic modification by cryopreservation in rat aortic allografts. Ann Thorac Surg 1995;60(Suppl):S168.
- Cochran R.P., Kunzelman K.S. Cryopreservation does not alter antigenic expression of aortic allografts. J Surg Res 1989;46:597-599.[Medline]
- Lupinetti F.M., Tsai T.T., Kneebone J.M., Bove E.L. Effect of cryopreservation on the presence of endothelial cells on human valve allografts. J Thorac Cardiovasc Surg 1993;106:912-917.[Abstract]
- Armiger L.C. Postimplantation leaflet cellularity of valve allografts: are donor cells beneficial or detrimental?. Ann Thorac Surg 1998;66(Suppl):S233.
- Kneebone J.M., Lupinetti F.M. Procollagen synthesis by fresh and cryopreserved rat pulmonary valve grafts. J Thorac Cardiovasc Surg 2000;120:596-603.[Abstract/Free Full Text]
- O’Brien M.F., Stafford E.G., Gardner M.A., et al. A comparison of aortic valve replacement with viable cryopreserved and fresh allograft valves, with a note on chromosomal studies. J Thorac Cardiovasc Surg 1987;94:812-823.[Abstract]
- Mitchell R.N., Jonas R.A., Schoen F.J. Structure-function correlations in cryopreserved allograft cardiac valves. Ann Thorac Surg 1995;60(Suppl):S108.
- Mitchell R.N., Jonas R.A., Schoen F.J. Pathology of explanted cryopreserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg 1998;115:118-127.[Abstract/Free Full Text]
- Rajani B., Mee R.B., Ratliff N.B. Evidence for rejection of homograft cardiac valves in infants. J Thorac Cardiovasc Surg 1998;115:111-117.[Abstract/Free Full Text]
- Vogt P.R., Stallmach T., Niederhauser U., et al. Explanted cryopreserved allografts: a morphological and immunohistochemical comparison between arterial allografts and allograft heart valves from infants and adults. Eur J Cardiothorac Surg 1999;15:639-645.[Abstract/Free Full Text]
- Wagner E., Roy R., Marois Y., et al. Fresh venous allografts in peripheral arterial reconstruction in dogs. Effects of histocompatibility and of short-term immunosuppression with cyclosporine A and mycophenolate mofetil. J Thorac Cardiovasc Surg 1995;110:1732-1744.[Abstract/Free Full Text]
- Legare J.F., Issekutz T., Lee T.D., Hirsch G. CD8+ T lymphocytes mediate destruction of the vascular media in a model of chronic rejection. Am J Pathol 2000;157:859-865.[Abstract/Free Full Text]
- Hawkins J.A., Bailey W.W., Dillon T., Schwartz D.C. Midterm results with cryopreserved allograft valved conduits from the right ventricle to the pulmonary arteries. J Thorac Cardiovasc Surg 1992;104:910-916.[Abstract]
- Clarke D.R., Campbell D.N., Hayward A.R., Bishop D.A. Degeneration of aortic valve allografts in young recipients. J Thorac Cardiovasc Surg 1993;105:934-942.[Abstract]
- Yankah A.C., Alexi-Meskhishvili V., Weng Y., et al. Accelerated degeneration of allografts in the first two years of life. Ann Thorac Surg 1995;60(Suppl):S71.
- Shaddy R.E., Hunter D.D., Osborn K.A., et al. Prospective analysis of HLA immunogenicity of cryopreserved valved allografts used in pediatric heart surgery. Circulation 1996;94:1063-1067.[Abstract/Free Full Text]
- Welters M.J., Oei F.B., Vaessen L.M., et al. Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation. Clin Exp Immunol 2001;124:353-358.[Medline]
- Shaddy R.E., Tani L.Y., Sturtevant J.E., et al. Effects of homograft blood type and anatomic type on stenosis, regurgitation and calcium in homografts in the pulmonary position. Am J Cardiol 1992;70:392-393.[Medline]
- Kadner A., Chen R.H., Mitchell R.N., Adams D.H. Hemograft crossmatching is unnecessary due to the absence of blood group antigens. Ann Thorac Surg 2001;71(Suppl):S349.[Abstract/Free Full Text]
- Fischlein T., Schutz A., Haushofer M., et al. Immunologic reaction and viability of cryopreserved homografts. Ann Thorac Surg 1995;60(Suppl):S122.
- Hoekstra F., Knoop C., Jutte N., et al. Effect of cryopreservation and HLA-DR matching on the cellular immunogenicity of human cardiac valve allografts. J Heart Lung Transplant 1994;13:1095-1098.[Medline]
- Hoekstra F., Knoop C., Aghai Z., et al. Stimulation of immune-competent cells in vitro by human cardiac valve-derived endothelial cells. Ann Thorac Surg 1995;60(Suppl):S131.
- Hoekstra F., Knoop C., Vaessen L., et al. Donor-specific cellular immune response against human cardiac valve allografts. J Thorac Cardiovasc Surg 1996;112:281-286.[Abstract/Free Full Text]
- Zhao X.M., Green M., Frazer I.H., et al. Donor-specific immune response after aortic valve allografting in the rat. Ann Thorac Surg 1994;57:1158-1163.[Abstract]
- Wagner E., Roy R., Marois Y., et al. Posttransplant antibodies and fresh venous allograft failure in dogs. Transplantation 1994;58:537-542.[Medline]
- Smith J.D., Ogino H., Hunt D., et al. Humoral immune response to human aortic valve homografts. Ann Thorac Surg 1995;60(Suppl):S127.
- Shaddy R.E., Thompson D.D., Osborne K.A., et al. Persistence of human leukocyte antigen (HLA) antibodies after one year in children receiving cryopreserved valved allografts. Am J Cardiol 1997;80:358-359.[Medline]
- Hoekstra F., Witvliet M., Knoop C., et al. Donor-specific anti-human leukocyte antigen class I antibodies after implantation of cardiac valve allografts. J Heart Lung Transplant 1997;16:570-572.[Medline]
- Breinholt J.P., III, Hawkins J.A., Lambert L.M., et al. A prospective analysis of the immunogenicity of cryopreserved nonvalved allografts used in pediatric heart surgery. Circulation 2000;102(Suppl 3):III179.
- Hoekstra F.M., Witvliet M., Knoop C.Y., et al. Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies. Ann Thorac Surg 1998;66:2022-2026.[Abstract/Free Full Text]
- Oei F.B., Welters M.J., Knoop C.J., et al. Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients. Eur J Cardiothorac Surg 2000;18:466-472.[Abstract/Free Full Text]
- Oei F., Dor F., Stegmann A., et al. Helper T cell frequencies after implantation of aortic valve allografts in rats. Transplant Proc 2001;33:640-641.[Medline]
- Legare J.F., Ross D.B., Issekutz T.B., et al. Prevention of allograft heart valve failure in a rat model. J Thorac Cardiovasc Surg 2001;122:310-317.[Abstract/Free Full Text]
- Yankah A.C., Wottge H.U., Muller-Ruchholtz W. Short-course cyclosporin A therapy for definite allograft valve survival immunosuppression in allograft valve operations. Ann Thorac Surg 1995;60(Suppl):S146.
- Bechtel J.F., Bartels C., Schmidtke C., et al. Does histocompatibility affect homograft valve function after the Ross procedure?. Circulation 2001;104(Suppl 1):I25.
- Elkins R.C., Lane M.M., Capps S.B., et al. Humoral immune response to allograft valve tissue pretreated with an antigen reduction process. Semin Thorac Cardiovasc Surg 2001;13(Suppl 1):82.[Medline]
- Steinhoff G., Stock U., Karim N., et al. Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue. Circulation 2000;102(Suppl 3):III50.
- Schmitz-Rixen T., Megerman J., Colvin R.B., et al. Immunosuppressive treatment of aortic allografts. J Vasc Surg 1988;7:82-92.[Medline]
- Vischjager M., Van Gulik T.M., De Kleine R.H., et al. Experimental arterial allografting under low and therapeutic dosages of cyclosporine for immunosuppression. Transplantation 1996;61:1138-1142.[Medline]
- Shaddy R.E., Lambert L.M., Fuller T.C., et al. Prospective randomized trial of azathioprine in cryopreserved valved allografts in children. Ann Thorac Surg 2001;71:43-48.[Abstract/Free Full Text]
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Abstract
Introduction
