Abstract
Graft coronary disease (GCD) is responsible for the majority of late deaths among
long-term heart transplant survivors. Noninvasive and invasive methods are too insensitive
to detect early stages of GCD and usually the diagnosis can be made after the occurrence
of considerable intimal proliferation. To assess the time course, distribution, and
extent of endothelial- and endocardial-directed cellular rejection we studied heterotopic
transplants of Lewis Brown Norway (LBN RT1n)F1 hearts into Lewis (LEW RT11) rats. Five groups were investigated: group 1 (n=13, killed 1–21 days post-Tx) no
immunosuppression; group 2 (n=11, 1–7 days) standard cyclosporine A (CsA) therapy;
group 3 (n=11, 14–69 days) CsA standard temporary (7 days); group 4 (n=6, 1–14 days)
low-dose CsA; group 5 (n=7, 1–100 days) isograft recipients, no immunosuppression.
Semiquantitative (score 0–3), immunohistochemical (W3/ 25, Ox-1, Ox-8, Ox-33, APAAP)
and qualitative histological analysis of small (SVV) and large vessel vasculopathy
(LVV) showed in all nonisogeneic groups that SVVâ©Ÿ1 occurred 7 days post-Tx. Endocardial
lymphocytic infiltrates appeared also in group 1, pointing to be CsA-independent and
representing endocardial rejection (ER). In most groups (groups 1, 2, 3), SVV preceded
LVV. Immunohistologically Ox-8+(CD8+) cells dominated in ER and SVV. In 92% of the
histological slides analyzed, the extent of SVV was homologous to ER. Isografts did
not develop SVV, LVV, or ER. We conclude that SVV and ER cannot be influenced by standard
CsA therapy. They can serve as early morphological indicators of GCD large vessel
therapy.
