Continuous administration of pharmacological agents in heterotopically transplanted hearts

A modification of the intraabdominal heterotopic heart transplantation model in rats is described which enables the local administration of pharmacological agents by means of a mini osmotic pump. In this modification, the aortic arch of the donor heart is cut after junction of the left carotid artery to enable the introduction of a catheter in the innominate artery. This catheter is connected to an implantable mini osmotic pump which delivers a continuous flow for 7 days. Radiographs of transplanted animals bearing pumps filled with a contrast agent showed that the coronary vessels of the graft were effectively perfused. Furthermore, continuous perfusion of prednisolone into the graft appeared to be as effective as subcutaneous infusion. Additional information about the usefulness of this perfusion technique is provided by recent data indicating that the expression of MHC class II antigens on vascular endothelium of a graft could only be evoked by interferon-gamma when it was locally administered into the graft. Our results demonstrate that this technique is suitable for investigating the effects of local, continuous administration of pharmacological agents on heart grafts.