Many children currently born with complex congenital heart disease cannot be adequately palliated by existing surgical techniques. Such lesions include variants of hypoplastic left or right heart syndrome and single ventricle. These children may have a potentially full life restored by transplantation but the optimal method of transplantation (orthotopic versus heterotopic) particularly in young infants is not known. The technical problems with small size, functional immaturity and adaptation, long-term graft survival, growth and optimal methods of immunosuppression must be addressed experimentally in appropriate fetal and neonatal models. At present the most limiting factor to clinical transplantation in children, particularly infants, is the availability of donor organs. We believe the use of vital organs from anencephalic fetuses may be a biologically superior, logistically simpler, and more cost effective solution. We also believe that soon the legal and ethical issues surrounding anencephalic donation will be favorably resolved. We have previously developed methods of using the fetal and neonatal heart as an auxiliary left heart bypass (left atrium to aorta) in immature pigs. We have refined our methods of harvest, preservation, anastomotic arrangement, and catheter placement for acute hemodynamic studies. This preparation can be done without the use of cardiopulmonary bypass, heparin, hypothermia, or circulatory arrest. We have achieved modest long-term survival (ten days) without immunosuppression. We now plan to use the immature pig model to 1) assess the relative output from the grafted and native heart using pressure transducers, electromagnetic flow probes, and radioactive microspheres, 2) determine the functional capacity of the neonatal donor heart to respond to acute manipulations of preload and afterload (using reversible occluders), 3) achieve long-term survival with immunosuppression, 4) to document growth, functional adaptation, and rejection, 5) to study chronic adaptation of the grafted heart to gradually increased functional demand produced by ameroid constrictor, and 6) to determine the best immunosuppression regimen to minimize the frequency and severity of rejection episodes and maximize growth of the immature animal.
