Acute xenograft rejection, late xenograft rejection and long term survival xenografts in the hamster-to-rat heart transplantation model: histological characterisation under low-dose of FK506.

BACKGROUND: Long-term survival studies have been conducted in hamster-to-rat cardiac models with a range of immunosuppressive treatments, but the histological pattern of Late Xenograft Rejection (LXR) has not been outlined. This study offers a detailed description of the histological changes in cardiac xenografts under three different immunological responses. MATERIALS AND METHODS: Heterotopic hamster-to-Lewis rat cardiac transplant. Recipients were administered an antiproliferative drug (MMF, 25 mg/kg, or CyP, 10 mg/kg, from day -7 to +7 or from day 0 to +7, according to group) and FK506 (0.2 mg/kg; from day 0 to +30 or continuously). Unmodified recipients were used as controls. Conventional histology and indirect immunofluorescence of IgM, IgG and C3 deposits were performed. RESULTS: In our study, xenografted rats that did not receive treatment developed a pattern of Acute Xenograft Rejection (AXR), with substantial tissue breakdown. Pretreated and treated animals until day 30 post-transplant developed LXR that may present two different histological patterns: one with vascular damage and predominant interstitial haemorrhage, and the other with extensive myocardial fibrosis. Long-term surviving rats (LTS) showed a morphology that was almost normal, with mild fibrosis and vascular endothelium preserved. CONCLUSIONS: AXR, LXR and LTS in the hamster-to-rat heart transplantation model present a common humoral mechanism although their histopathological patterns are different depending on the length of immunosuppressive treatment but not on the type of antiproliferative drug administered. Pretreatment exerts an effect on fibrosis formation.