For our opening post I’ve homed in on some specimens that are interesting because of their place in medical history, specifically the history of xenotransplantation.

After his exceedingly well known first human heart transplant in 1967, Dr Chris Barnard continued experimenting. The rationale for the “piggy-back heart transplant” or heterotopic cardiac transplant is clear from this excerpt:

“In 1973, Barnard performed a heart transplant and the donor heart failed to function satisfactorily, so the patient died in the operating theatre. When Barnard came out to break the sad news, he was asked why he could not put the old heart back, as at least it had kept the patient alive. This struck Barnard as a distinct possibility. If the patient’s own heart had been left in place, and the transplant was inserted as an auxiliary pump, failure of the donor heart may not have caused the patient’s demise. Furthermore, during severe rejection episodes, which were common in those early days and a major cause of the poor results at the time, the native (i.e. patient’s own) heart might be able to maintain the circulation while rejection was reversed by increased therapy.”¹

One thing led to another:

“On two occasions in 1977, when a patient’s left ventricle failed acutely after routine open-heart surgery and when no human donor organ was available, Barnard transplanted an animal heart heterotopically. On the first occasion, a baboon heart was transplanted, but this failed to support the circulation sufficiently, the patient dying some six hours after transplantation. In the second patient, a chimpanzee heart successfully maintained life until irreversible rejection occurred four days later, the recipient’s native heart having failed to recover during this period. Further attempts at xenotransplantation were abandoned and even now, more than 30 years later, xenotransplantation remains an elusive holy grail despite decades of research.”¹

These are those two ragged-looking but seminal xenotransplants, preserved in the UCT pathology teaching collection:

Barnard’s own report of these two cases makes fascinating reading².

In a similar vein, and from a similar time, this liver specimen dated 1968 is from a patient who suffered severe (sub)acute liver failure and went into coma. The catalogue description reads: “The liver is seen to be markedly reduced in size (885g), with the bulk of the surviving regenerated liver present as a large mass in the right lobe with occasional smaller nodules present elsewhere; the left lobe is shrunken, and slightly congested.”

But what is notable about this case is that a baboon liver perfusion had been performed, though unfortunately without response. The objective would have been to try to tide the patient over the acute liver failure, giving their own liver a chance to regenerate enough to resume functioning – analogous to the use of transient renal dialysis in acute kidney failure.

Between 1964 and 1970, one hundred and thirteen patients who had received extracorporeal liver perfusion or ECLP were reported (this case not among them). By 2000 the number reported was 270. Pig livers were most often used, but on review, baboon or human livers gave better long term survival (≈40% vs. ≈20%). But during this period the overall survival of acute liver failure patients receiving ECLP was no better than that of patients receiving conventional intensive care (≈25% for both)³. Today, artificial and bioartificial liver support can be part of the intensive care for acute liver failure, often as a bridge to liver transplantation, the optimal treatment.  ELCP using whole human livers (not suitable for transplant) or transgenic pig livers is still an option for temporary liver support in this context, despite the technical challenges and concerns about the risk of transmission of infectious agents⁴.

The availability of non-human primates for medical research is now far more limited than it was in the second half of the 20th century from when these cases date, but aside from non-human primates, other animals appear to remain “fair game” in the modern field of xenotransplantation.

See also

 http://www.humanxenotransplant.org

Benatar D. Duty and the beast: animal experimentation and neglected interests. Q J Med 2000: 93:831-835

References

1. Brink JG, Hassoulas J. The first human heart transplant and further advances in cardiac transplantation at Groote Schuur Hospital and the University of Cape Town. Cardiovasc J Afr. 2009; 20(1):31-5
2. Barnard CN, Wolpowitz A, Losman JG. Heterotopic cardiac transplantation with a xenograft for assistance of the left heart in cardiogenic shock after cardiopulmonary bypass. S Afr Med J. 1977; 52(26):1035-8.
3.  Pascher A, Sauer IM, Hammer C, Gerlach JC, Neuhaus P. Extracorporeal liver perfusion as hepatic assist in acute liver failure: a review of world experience. Xenotransplantation 2002: 9: 309–324 
4. Naruse K, Nagashima H, Sakai Y, Kokudo N, Makuuchi M. Development and perspectives of perfusion treatment for liver failure. Surg Today. 2005; 35:507–517