Direct gene transfer into donor hearts at the time of harvest.

Access to the donor heart at the time of harvest provides a unique opportunity for genetic manipulation of this organ before transplantation. We sought to determine (1) if donor mouse hearts express a foreign gene administered at harvest and, (2) if so, what route of gene delivery is most effective. At harvest, 30 micrograms of promoter cytomegalovirus-luciferase deoxyribonucleic plasmid in cationic liposomes was injected directly into the myocardial apex (group I), into the right atrium (group II), or into the coronary arteries (group III). The donor hearts were then transplanted into the abdomen of recipient mice of the same strain. The transplanted hearts were removed in 4 days and luciferase expression was assayed by immunohistochemistry. In group I, luciferase activity was localized to the apex. In group II, where plasmid was delivered into the right atrium, luciferase expression was detected in the right ventricle and sparsely in the coronary perivascular area. In group III, where plasmid was injected into the coronary arteries, the transplanted hearts demonstrated luciferase expression in (1) perivascular areas surrounding coronary arteries and veins, (2) coronary capillaries, and (3) the endocardia of both ventricles. This study suggests that (1) donor mouse hearts can be genetically modified at the time of harvest and (2) intracoronary infusion of plasmid yields the most effective method of delivery. Administration of plasmid in the coronary arteries localizes the expression to the endocardium and the coronary vasculature, both sites of immunologic interactions after heart transplantation.