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Neal D. Hillman
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J Thorac Cardiovasc Surg 2003;126:247-252
© 2003 The American Association for Thoracic Surgery

Surgery for congenital heart disease

Immunogenicity of decellularized cryopreserved allografts in pediatric cardiac surgery: comparison with standard cryopreserved allografts

John A. Hawkins, MDa,*, Neal D. Hillman, MDa, Linda M. Lambert, MDa, Jamison Jones, MDa, Gregory B. Di Russo, MDa, Tracie Profaizer, BSc, Thomas C. Fuller, PhDc, L. LuAnn Minich, MDb, Richard V. Williams, MDb, Robert E. Shaddy, MDb

a Department of Pediatric Cardiothoracic Surgery, Primary Children’s Medical Center and University of Utah, Salt Lake City, Utah, USA
b Department of Pediatric Cardiology, Primary Children’s Medical Center and University of Utah, Salt Lake City, Utah, USA
c Histocompatibility and Immunogenetics Laboratory, University of Utah Hospital, Salt Lake City, Utah., USA

Read at the Eighty-second Annual Meeting of The American Association for Thoracic Surgery, Washington, DC, May 5-8, 2002.

Recieved for publication June 7, 2003 Received for publication August 1, 2002; revisions received September 16, 2002; accepted for publication October 10, 2002.

* Address for reprints: John A. Hawkins, MD, Pediatric Cardiothoracic Surgery, Primary Children’s Medical Center, 100 N Medical Dr, Salt Lake City, UT 84113, USA
jhawkins{at}med.utah.edu

BACKGROUND: Recognition of the immunogenicity of standard cryopreserved allografts has led to the development of new decellularized allografts (CryoValve SG; CryoLife, Inc, Kennesaw, Ga). This preliminary study examined the HLA antibody response to these decellularized allografts and compared it with the response to standard allograft material.

METHODS: We prospectively measured the frequency of panel-reactive HLA class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DR/DQ) alloantibodies in 14 children (age 8.5 ± 7.9 years) receiving decellularized, cryopreserved allografts, including 6 undergoing allograft patch insertion and 8 with a valved pulmonary allograft. We compared them with 20 historical control subjects (age 1.7 ± 2.4 years) undergoing implantation of standard cryopreserved allografts, 8 with valves and 12 with allograft patch. All patients had panel-reactive antibody levels measured before and at 1, 3, and 12 months after the operation. HLA class I and class II panel-reactive antibody levels were determined with a sensitive flow cytometry technique.

RESULTS: We found panel-reactive antibody levels in decellularized allografts to be elevated slightly from preoperative levels for both class I and class II antibodies at 1, 3, and 12 months (P > .05). The panel-reactive antibody level for both class I and class II antibodies were significantly lower for decellularized allografts as compared to standard allografts. Functionally, the allografts were similar with decellularized valved grafts showing a peak echo-determined systolic gradient of 13 ± 15 mm Hg at 8 ± 2.6 months postoperatively as compared to a gradient of 24 ± 18 mm Hg measured 12 ± 6 months postoperatively in standard allografts (P = .11).

CONCLUSIONS: Decellularized grafts elicited significantly lower levels of class I and class II HLA antibody formation at 1, 3, and 12 months after implantation than did standard cryopreserved allografts. Early hemodynamic function of decellularized grafts was similar to that of standard cryopreserved allograft valves. Further experience is necessary to determine whether the reduced immunogenicity of decellularized allografts will truly allow tissue ingrowth and improved long-term durability in patients.


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Discussion
J. Thorac. Cardiovasc. Surg. 2003 126: 252-253. [Extract] [Full Text] [PDF]



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