ACI Donors Research Articles

The influence of dose and dose rate of total lymphoid irradiation in the rat cardiac allograft model

Immunosuppression generated by total lymphoid irradiation (TLI) may be of use in solid organ transplantation. We have investigated the use of TLI in the rat cardiac allograft model. Lewis rats received TLI from a cobalt-60 machine. The daily dose was 1.25 Gy and treatments were administered 4 days per week. We performed experiments to assess the effect of dose rate upon graft survival. The dose rate was varied by changing the source to animal distance and by using a lead attenuator. Cardiac allografts from each ACI donor rat were transplanted to the recipient Lewis rat's abdomen utilizing microvascular surgical technique. Heart graft survival times (GST) were monitored by direct palpation of the cardiac impulse. Immune function was measured by an activity index of the mixed lymphocyte reaction. In the absence of any immunosuppression there was a mean GST of 6.9 +/- 0.3 days. When a graft was placed the day following completion of TLI, there was an increase in GST as the total TLI dose was increased. Mean GST (+/- S.E.) following 5, 10, and 15 Gy were 12.3 +/- 1.3, 14.5 +/- 1.3, and 25.5 +/- 1.1 days, respectively. Following 20 Gy, GST decreased because of irradiation induced pulmonary toxicity and host death. When 3.5 weeks were allowed to elapse between the completion of TLI and transplantation, GST were less than those seen with equivalent doses of TLI and early transplantation. Mean GST following 5, 10, and 15 Gy and a delayed transplant were 7.2 +/- 0.1, 10.7 +/- 1.2, and 19.0 +/- 3.5 days, respectively. We tested the effect of dose rate upon GST.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic transplantation into sensitized recipients. Demonstration of hyperacute rejection.

Hepatic transplantation into humorally presensitized patients has occasionally been performed without reported accelerated rejection. To study survival of orthotopic hepatic transplants in sensitized recipients a series of studies in rats were performed. Lewis rats sensitized by three successive skin grafts from fully allogeneic ACI strain donors then underwent orthotopic hepatic transplantation from ACI donors. Nine of ten recipients died within 4 hr with bleeding from the liver surface. By comparison, nine unsensitized recipients survived a mean of 10.7 +/- 0.5 days before succumbing with cellular rejection. Death of the sensitized recipients was not due to coagulopathy or technical failure. Histological studies of hyperacutely rejected livers demonstrated marked hemorrhage, edema, congestion, and necrosis within the hepatic parenchyma. There was a relative lack of cellular infiltrate compared with livers rejected by unsensitized recipients. Immunofluorescent staining showed IgG bound to perivascular tissues and sinusoids, and complement bound to perivascular tissue. Serum from presensitized, but not control, recipients showed a high titer of donor-specific, complement-dependent cytotoxic activity. It is concluded that hyperacute rejection of hepatic transplants can occur in sensitized rats and is mediated by a humoral mechanism. The immunohistopathology of this process is described.

Donor-specific blood transfusions with stored and fresh blood in a rat heart allograft model

Donor-specific transfusions (DSTs) using stored and fresh blood were investigated in a rat heart allograft model. Lewis rats were recipients of preoperative DSTs and cardiac allografts from ACI donors. Blood was stored for 0, 1, 2, 3, 4, and 5 weeks prior to transfusion. Allograft survival and recipient sensitization were recorded. In all DST groups, allograft survival was superior to nontransfused controls ( P < 0.05). Stored blood was equal or better than fresh blood, and a 2-week storage was optimal ( P < 0.05). Storage of 2 weeks or greater resulted in decreased sensitization compared to storage for 1 week or less ( P < 0.05). This study supports the use of stored blood to enhance allograft survival and reduce recipient sensitization.

Extended allograft survival of islets grafted into intra-abdominally placed testis.

Isolated islets of ACI donor rats were cultured for 4 days at 37 degrees C and then grafted into male diabetic Wistar-Lewis rats into three different organ sites without adjuvant immunosuppression. None of 6 recipients of the intraportal injection of 10 islets per gram of body weight became normoglycemic. Similarly, six rats that received islets injected under the renal capsule remained diabetic. None of six rats that received an intratesticular islet allograft became normoglycemic while these organs remained within the scrotum. By contrast, six rats that were transplanted with an identical number of islets into the testis, which were then surgically placed into the abdominal cavity, promptly became aglycosuric and have remained so for more than 50 days.

Bone marrow transplantation in the busulfin-treated rat. III. Relationship between myelosuppression and immunosuppression for conditioning bone marrow recipients.

Lewis rats were given graded doses of cyclophosphamide (CY) alone or in combination with graded doses of busulfan (BU), rabbit anti-rat thymocyte serum, or BU plus rabbit anti-rat thymocyte serum, and transplanted with bone marrow from syngeneic or allogeneic Ag-B-incompatible ACI donors. Another gr