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Despite major advances in the treatment of severe myocardial failure, a sizable number of patients with terminal or progressive myocardial dysfunction are fated to die or be severely limited by symptoms. In these patients, biological replacement of the heart (cardiac transplantation) has become standard therapy and is widely accepted as a modality for prolonging life and improving its quality in carefully selected patients. As technologic and engineering advances occur, support or replacement of the heart by mechanical devices (mechanical circulatory support) is additionally providing alternative or complementary treatment modalities for many of these patients.

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Interest in developing surgical techniques to interpose a functioning heart into a recipient's circulation dates back at least to the early part of the twentieth century. In 1905, Carrel and Guthrie1 described the heterotopic transplantation of a functioning donor heart into the neck of a dog. The heart in that model functioned together with the recipient's heart in the circulation but was not capable of supporting the circulation. Although the exact anatomic connections were not described in detail, this apparently nonworking model of heterotopic transplantation beat regularly for approximately 2 hours before the blood clotted in all of the chambers. Carrel Guthrie2 developed innovative surgical techniques for vascular anastomosis at the University of Chicago, and those advances set the stage for anastomosis, leading to organ transplantation. This work was partially responsible for Carrel's being awarded the Nobel Prize for medicine and physiology in 1912.

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It was not until 1933 that Mann and coworkers3 at the Mayo Clinic published their seminal report of a technique for heterotopic heart transplantation with circulatory loading of the RV. Because this was a working model, the chambers did not clot immediately, and the hearts in their dogs beat for a mean of 4 days. Mann and coworkers perceived several important surgical points, including the importance of avoiding ventricular distention and air embolism and the prevention of thrombosis by heparin. Their most incisive observation was that failure of a transplanted heart was not always caused by faulty surgical technique “but to some biologic factor which is probably identical to that which prevents survival of other homotransplanted tissues and organs.“ In what was undoubtedly the first description of acute allograft rejection, Mann and coworkers recount: “When the heart was removed just before it became quiescent . . the surface of the heart was covered with mottled areas of ecchymoses . . histologically the heart was completely infiltrated by large mononuclears and polymorphonuclears.“3 It took another 30 years to understand and manipulate the “biologic factor“ these authors had described as limiting the survival of allograft organs. In 1960, Lower and Shumway4 performed orthotopic heart transplants in dogs using cardiopulmonary bypass and topical hypothermia for donor heart preservation. The dogs survived between 6 and 21 days and died of rejection. Lower and Shumway also recognized that “if the immunologic mechanisms of the host were prevented from destroying the graft, in all ...

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