3
Background

The Historical NHBD

After unsuccessful attempts at solid organ transplantation in the early 1950s, the successful transplantation of a kidney from one identical twin to the other in 1954 reassured scientists that the actual technical transfer of a major functioning solid organ from one person to another was a practical possibility. The biological and immunological problems that remained were at least in part identified, if by no means fully understood or resolved. The success of a kidney transplant between fraternal twins in 1959 suggested that these were not insurmountable either, and indeed, existing and subsequently developed drugs mitigated the effects of the immune response, delaying or preventing rejection of the transplanted organ. The development of immunological tests, including tissue typing and matching, also played a role in improving results. Experimental transplant programs started with kidney transplantation, to which were added liver (1963) and heart (1967) transplantation along with pancreas, lung, various combinations such as kidney-pancreas and heart-lung, and more recently intestine (DeVita et al., 1993; Federle, 1995; Starzl and Demetris, 1995).

Early transplant programs obtained organs either from healthy, living, related donors or from cadaver donors. These cadaver donors were declared dead by cardiopulmonary criteria. A determination of death by neurologic criteria, although a legal option in the sense that state laws allowed physicians to make determinations of death according to their own practice and custom, was not generally accepted. Physicians of the time were reluctant to pronounce death in a patient who had continued heart function. Such cadaver donors provided kidneys most commonly, although there were some successful attempts to transplant other solid organs.



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--> 3 Background The Historical NHBD After unsuccessful attempts at solid organ transplantation in the early 1950s, the successful transplantation of a kidney from one identical twin to the other in 1954 reassured scientists that the actual technical transfer of a major functioning solid organ from one person to another was a practical possibility. The biological and immunological problems that remained were at least in part identified, if by no means fully understood or resolved. The success of a kidney transplant between fraternal twins in 1959 suggested that these were not insurmountable either, and indeed, existing and subsequently developed drugs mitigated the effects of the immune response, delaying or preventing rejection of the transplanted organ. The development of immunological tests, including tissue typing and matching, also played a role in improving results. Experimental transplant programs started with kidney transplantation, to which were added liver (1963) and heart (1967) transplantation along with pancreas, lung, various combinations such as kidney-pancreas and heart-lung, and more recently intestine (DeVita et al., 1993; Federle, 1995; Starzl and Demetris, 1995). Early transplant programs obtained organs either from healthy, living, related donors or from cadaver donors. These cadaver donors were declared dead by cardiopulmonary criteria. A determination of death by neurologic criteria, although a legal option in the sense that state laws allowed physicians to make determinations of death according to their own practice and custom, was not generally accepted. Physicians of the time were reluctant to pronounce death in a patient who had continued heart function. Such cadaver donors provided kidneys most commonly, although there were some successful attempts to transplant other solid organs.

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--> Kidneys, as the primary organs recovered from these cadavers, generally had been exposed for a considerable period of time (by today's standards) to failing circulation and did not approach the ideal—perfusion with warm, oxygenated blood up to the time of removal from the donor. Results were understandably below current expectations. Somewhat damaged kidneys suffered frequently from delayed function in the recipient, as is observed particularly in NHBD kidneys today. Such kidneys experience acute rejection more often and have poorer long-term survivals (Troppmann et al., 1996). Nevertheless, early versions of organ perfusion and preservation technologies similar to those currently in use were developed, and transplantation using these (uncontrolled) NHBDs continued to be pursued in Japanese and some European centers (Anaise and Rapaport, 1993). Neurologic Criteria For Death In 1968, the Harvard neurologic definition and criteria for death were published (Report of the Ad Hoc Committee of the Harvard Medical School, 1968). These essentially amounted to total unresponsiveness and loss of the brain's integrative control of body physiology as measured by various clinical and technical tests. Over the next few years, a model definition of death based on irreversible loss of function of the whole brain including the brain stem, or irreversible cessation of cardiopulmonary function, was enacted widely into state law, enabling the recovery of organs from "brain-dead" cadavers who maintained breathing and circulation on artificial ventilation. Organs recovered from these donors were viable and were more likely to function well immediately and to yield good long-term results. As a result, the original approach of recovering organs from NHBDs gradually ceased to be a significant part of transplantation in the United States and many Western countries. Brain death is now legally and ethically accepted in every state. However, there are still some misconceptions about the whole-brain determination of death, for example: (1) many practitioners do not know and do not practice the correct determination of brain death (Mejia and Pollack, 1995); (2) some varying technical signs of brain function often persist in brain-dead patients (Halevy and Brody, 1993); (3) physicians and others often speak in ways that imply that there is brain death and then real death when heart and lung function is lost, and they use the time of the latter as the time of death for death certificates; (4) surveys and questionnaires indicate that about a third of physicians, some donor families, and certainly many in the general public do not really understand the concept of brain death (Gallup, 1993; Youngner et al., 1989); and (5) it is difficult for many to consider a donor dead whose heart is still beating and whose respiration continues, even though circulation and other normal body functions can be maintained only artificially and with difficulty (Arnold and Youngner,

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--> 1993; Field et al., 1988; Parisi et al., 1982). Nevertheless, despite these conceptual difficulties, the use of brain-dead (heart-beating) donors has been widely accepted at present in the United States and is the basis for a part of the improved results of transplantation.* *   Acceptance of the concept of brain death is not universal. There are rare, spirited objections (McMahan, 1995).