[Mechanisms of rejection in guinea pig (GP)-to-rat liver xenotransplantation: improvement of recoloration of GP liver graft and effects of perfluorochemical (FC43) in GP-to-rat liver xenotransplantation].

The impaired reperfusion after revascularization has not allowed guinea pig (GP)-to-rat liver xenograft model to be widely used for xenotransplant research. This study was designed to clarify mechanisms responsible for the impaired recoloration, and to examine effects of FC43 emulsion, an anti-complement agent. 1) Mechanisms responsible for the impaired recoloration: GP allogeneic and xenogeneic liver grafts flushed with 4 degrees C lactated Ringer's (LR) solution were poorly perfused around the porta hepatis, whereas those flushed with 15 degrees C LR solution were immediately recolored, this being confirmed by portal venography. The recoloration was also ameliorated by reduction of ischemic time. Even recolored GP xenografts, turned uneven dark gray however, and enlarged around 5 min after revascularization. Histological and immunohistological findings of GP livers 1 h after xenografting were characteristic of sinusoidal congestion and hepatocytes necrosis, and the livers had remarkable C3 deposits on sinusoids and central veins, IgM deposits faintly stained on some small vessels but no detectable deposits of IgG. 2) Effects of FC43. Administration with of either a single dose of 10 microliters/g or repeated doses of 5 microliters/g of FC43 resulted in significant prolongation of xenograft survivals compared with controls (8.06 +/- 1.45, 9.45 +/- 3.64 vs. 4.23 +/- 0.89 h; p < 0.02), thereby sustaining almost normal gross appearances until abdominal closures. Thus, the onset of hyperacute rejection (HAR) was postponed by FC43 administration; however, all rats died within 14 h. No deposit of C3 was detected in GP xenografts of FC43 groups, while deposits of granulocytes and macrophages (M phi) were observed from 1 and 3 h after revascularization, respectively. In conclusion, the impaired recoloration in this model may be due to physiological defects during the initial stage of revascularization, which is followed by the immunological responses that probably involved M phi and granulocytes. The present study indicates that discordant GP liver xenotransplantation is feasible as a useful rodent model for either exploration of mechanisms of immunological responses or examination of the immunosuppressive effects of pharmacological agents.