Heterotopic cardiac xenotransplantation: fish-to-rat

The purpose of this study was to determine whether a vascularized organ transplanted from a teleost fish to a rodent would be hyperacutely rejected. Previous reports describing the results of discordant xenotransplantation are almost exclusively across orders within the class Mammalia. We chose a species combination that crosses many phylogenetic barriers (i.e. species, genus, family, order, and class) as well as several hundred million years on an evolutionary timescale. Because no published methodology existed, we developed a microvascular surgical method for fish (tilapia)-to-rat heterotopic cardiac xenotransplantation. To minimize the blood pressure to which the graft would be exposed, the tilapia heart was placed on the venous side of the rat circulation between the left kidney and the inferior vena cava by end-to-side anastomoses of the donor aorta to the recipient inferior vena cava and by end-to-end anastomosis of the donor sinus venosus to the recipient left renal vein. Tilapia hearts were rejected hyperacutely, based on both routine histopathological examination and immunofluorescent staining for immunoglobulin and complement, but rejection required hours rather than minutes.