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Relationship between MHC II expression on T-lymphocytes and rejection : a model of heterotopic heart transplantation

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Title: Relationship between MHC II expression on T-lymphocytes and rejection : a model of heterotopic heart transplantation
Author: Kaderabek, Radek Ctirad
Degree Master of Science - MSc
Program Surgery
Copyright Date: 2004
Abstract: Introduction: The method of choice for monitoring post-transplant rejection status for heart transplant patients is the evaluation of multiple tissue biopsies. The diagnostic technique is time consuming, costly and invasive with possible life threatening complications. The major histocompatibility complex is the most widely distributed and significant determinant for transplantation. We hypothesized that the MHC II expression on peripheral T-lymphocytes is reflective of rejection status in allotransplanted hearts. The objective of this project is to determine if MHC II expression on peripheral Tlymphocytes correlates with histological findings of rejection after transplantation. Materials and methods: The heterotopic heart transplant was performed in 24 female domestic swine, weighing 27-30 Kg. Animals were divided into two groups. Group A (6 donors + 6 recipients) was not treated with immunosuppressive therapy. In group B (6 donors + 6 recipients) immunosuppressive therapy (Cyclosporine 6mg/Kg/BID, Methylpednisolone 1.8mg/Kg/day and Azathioprine 3mg/Kg/day) was used. Cyclosporine levels in blood were maintained at 400 ng/mL. Donor animals were anaesthetisized and the heart was harvested through a median sternotomy. The hearts were antegradely perfused with isoosmolar Tyers's solution and were then preserved in a hypothermic storage for two hours at 4°C. In the postoperative period animals were monitored by ECG, heart-rate, body temperature, blood samples for MHC II expression, cyclosporine levels, CBC plus differential and creatinine daily . Animals in Group A, survived for a period of five days and animals in Group B, where immunosuppressive therapy was applied, survived for five days also. The endomyocardial biopsies (EMB) were taken from the graft's free wall, apex and septum on day one and five for both groups A and B. The evaluation of #120 EMB (biopsies) was done using modified International Society Heart and Lung Transplant Grading Scale. Results: Results of this experimental endeavour demonstrated that MHC II expression on T-lymphocytes significantly correlates with biopsy findings from apex (P<0.01; R² = 0.83) for Group A (non-immunosuppressed animals) on day five. The combined data for both Groups A and B (non-immunosuppressed and immunosuppressed animals) at this time were also correlated significantly (P<0.01; R² = 0.63) for free wall and (P=0.01; R² =0.7) for apex despite a significant difference between non-immunosuppressed and immunosuppressed animals. Conclusions: Results of this experimental protocol suggested that there is a significant correlation between MHC II expression on peripheral T-lymphocytes and Grade of rejection assessed by endomyocardial biopsy on day five after surgery. Further studies will be required to establish the long term relationship of MHC II expression on peripheral T-lymphocytes and histological findings, particularly in animals with immunosuppressive therapy.
URI: http://hdl.handle.net/2429/16256
Series/Report no. UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/]

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