Donor heart preservation for heart transplantation

Heart transplantation has enjoyed a spectacular success over the past 25 years. Prior to 1980 less than 350 operations were carried out with an overall one year survival of less than 60%. In 1995 more than 3,000 transplants were performed with a one year survival of 83%. However, growth and improved survival have both plateaued over the last few years; the former because of the falling donor supply and the latter, in part, because of the use of less suitable donors in an effort to offset the problem of supply. Much attention has been focused on the drama of the surgery and the intricacies of immunological manipulation whilst little effort has been devoted to the area of donor management, despite the fact that primary graft failure is responsible for as many post transplant deaths as either infection or rejection. Optimum preservation of the donor heart has also provided a difficult challenge, such that, despite a considerable scientific effort little advance has been achieved to extend the 4 hour safe storage limit which has remained in place over the past 20 years. In this dissertation the problem has been approached by combining laboratory based preservation models with an objective regime of donor management. A sensitive isolated small animal working heart model was developed and used to characterise cardioplegic induction. Subsequently, the model was used to examine the interaction of oxygen content with the mode of delivery, during preservation. Finally, a number of representative solutions were combined with the most promising oxygen delivery method. These studies served to illustrate the utility of controlled laboratory studies and offer the prospect of more than doubling post storage function. The development of a rigorous donor management regime was also shown to be capable of reducing the variance in haemodynamic parameters by up to 44% whilst safely increasing the donor pool by approximately 30%. It is the contention of this thesis that the only prospect of improving the current impasse with the supply of donor hearts in sufficient quantity and of acceptable quality, is by the combination of appropriate laboratory models with controlled clinical trials