Rat Aortic Allografts Research Articles

Chronic rejection of rat aortic allograft: II. Administration of cyclosporin induces accelerated allograft arteriosclerosis

Rat aortic allografts immunosuppressed with cyclosporin--but not with azathioprine or steroids--develop an early inflammatory lesion in the subendothelial space. This "endothelialitis" is followed by an influx of proliferating smooth muscle cells into the intima, resulting in intimal thickening and accelerated arteriosclerosis. Administration of azathioprine and steroids largely ameliorates the development of the accelerated lesion. Similar endothelialitis and accelerated arteriosclerosis have been observed previously in the autopsy material of cardiac transplant recipients. Our results confirm the suggestion that the development of accelerated allograft arteriosclerosis is most likely linked to cyclosporin administration.

Effect of storage at 4 °C in a nutrient medium on antigenic properties of rat aortic valve allografts

The effects of prolonged storage at 4 °C in nutrient medium on the antigenic properties of aortic valve allografts are unknown. Lewis rats received heterotopic aortic valve allografts from Brown Norway donors. Valves were transplanted immediately after harvest (fresh), or after antibiotic sterilization and storage in a nutrient medium at 4 °C for 3, 7, 14, or 21 days. Additional rats underwent sham laparotomy (sham). All recipient rats received Brown Norway skin grafts 3 weeks after valve transplant or sham procedure. Time to skin graft rejection for all groups was as follows: fresh (n = 10), 4.5 ± 0.9 days; sham (n = 10), 7.1 ± 0.3 days; 3-day (n = 10), 4.9 ± 0.3 days; 7-day (n = 10), 5.2 ± 0.4 days; 14-day (n = 10), 6.1 ± 0.7 days; and 21-day (n = 10), 6.0 ± 0.6 days. Significant differences existed between the sham group and each of the transplanted groups. No significant differences existed between the fresh group and either the 3-day or 7-day groups. The difference between the fresh group and the 14-day group approached significance (0.05 < p < 0.10), and the difference between the fresh and 21-day groups was significant ( p < 0.05). Additional valves not used for transplantation were studied with scanning electron microscopy. The valves preserved in nutrient medium exhibited a progressive loss of endothelium as compared with fresh valves. Storage of aortic valve allografts in a nutrient medium at 4 °C is associated with a progressive attenuation of antigenic response. The loss of antigenicity appears to plateau, however, and the grafts remain immunogenic even after 3 weeks. Loss of endothelial integrity may explain the change in immunological effect.