TY - JOUR
T1 - Late cyclosporine treatment ameliorates established coronary graft disease in rat allografts
AU - Handa, Nobuhiro
AU - Hatanaka, Masataka
AU - Baumgartner, William A.
AU - Reitz, Bruce A.
AU - Sandford, Gordon
AU - Esa, Ahmed H.
AU - Herskowitz, Ahvie
PY - 1993/9
Y1 - 1993/9
N2 - The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n=29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n=17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.
AB - The development of post-transplantation coronary graft disease (CGD) is a major cause of late morbidity and mortality. Recent reports have suggested that CGD is a type of chronic vascular rejection, possibly enhanced by cofactors such as concurrent CMV infection and hyperlipidemia. It remains controversial whether established CGD can be improved by modifications in immunosuppressive therapy. The purpose of this study was to examine whether CsA could reverse or halt the progression of CGD after it was already established. Lewis to Fisher (F-344) heterotopic heart allografts develop CGD resembling human disease. Group 1 (n=29) had no CsA therapy for chronic rat CMV (RCMV) infection in recipients for 8 weeks before transplant. Group 2 (n=17) had chronic RCMV infection along with CsA therapy from days 15 to 28 post-transplant. Allografts were killed at 2 and 4 weeks and 90 days post-transplantation. In group 1, leukocyte adhesion to arterial endothelium and intimal hyperplasia were well established at 2 weeks and progressed to stenotic, proliferative arterial lesions at 4 weeks. In group 2, CsA therapy was effective in significantly reversing histologic parameters of vascular rejection such as leukocyte adhesion, intimal proliferation, and periarterial edema at 4 weeks. By 90 days, however, arterial pathology was as severe as in group 1. In conclusion, these results support the hypothesis that CGD is a form of chronic vascular rejection, and once established, can be significantly modified by CsA therapy. These effects are not permanent, and progressive CGD recurs after CsA therapy is discontinued.
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U2 - 10.1097/00007890-199309000-00009
DO - 10.1097/00007890-199309000-00009
M3 - Article
C2 - 8212146
AN - SCOPUS:0027386206
SN - 0041-1337
VL - 56
SP - 535
EP - 540
JO - Transplantation
JF - Transplantation
IS - 3
ER -