Transplant coronary artery disease - A novel model independent of cellularalloimmune response

Background-Allograft coronary atherosclerosis (TxCAD) is the leading cause of death after the first year after transplantation. TxCAD is believed to b e a form of chronic rejection of the cardiac allografts. This study was und ertaken to determine whether TxCAD could develop in the absence of a cellul ar alloimmune response. Methods and Results-Inbred lean Zucker rats (> 26 generations) served as do nors and recipients of the cardiac grafts. Donor hearts were explanted at 6 0 or 90 days. Explanted hearts were processed for coronary artery histologi cal analysis. Cytokine expression was determined by reverse transcription-p olymerase chain reaction, and the presence of T cells within the explanted hearts was evaluated by immunohistochemistry. Forty-six transplantations we re made, and TxCAD developed in all but one of the transplanted hearts. Ove rall, one third of the vessels examined were affected by TxCAD, and in roug hly half of these vessels, the disease was severe. Native hearts were free of atherosclerosis. Interleukin-2 was absent from the transplanted hearts, and T cells were present in minimal amounts (<1 per low-power field). Conclusions-TxCAD developed in the absence of a cellular alloimmune respons e in these genetically similar donors and recipients. The observed TxCAD wa s significant and comparable to what is found in rat allografting models.