Failed Pig Heart Transplant Yields Unexpected Insights

Failed Pig Heart Transplant Yields Unexpected Insights

(Photo: University of Maryland)
At the beginning of the year, we reported on an exciting yet precarious : the transplant of a pig heart into a human patient. The experiment unfortunately didn’t end as optimistically as it started, with the recipient showing “signs of acceptance” in the first few days but passing away two months later. Researchers immediately got to work determining what went wrong. Now, the potential reasons for the transplant’s failure are detailed in a paper published Friday in the New England Journal of Medicine.

David Bennett, a 57-year-old man with terminal heart disease, was considered an appropriate xenotransplantation recipient because of (not despite) the rapid and aggressive progression of his illness.

Bennett’s medical state prevented him from being eligible for four individual human heart transplant programs. What appeared to be a hopeless situation became a bit more promising when scientists deemed Bennett—who was, at the time, kept alive through an external blood oxygenation device—eligible for the pig heart experiment. 

The pig heart in question was a product of Revivicor, a firm that genetically engineers “xeno-organs” for medical transplants. Revivicor modified 10 of the pig hearts’ genes prior to the procedure. In the realm of xenotransplantation, genetic modification has two primary goals: to boost the likelihood of organ acceptance and to eliminate room for viruses (in this case, porcine endogenous retrovirus C, or PERV-C). Revivicor allegedly verified that the organ was free of PERV-C prior to transplant; Bennett likewise did not show signs of the virus after surgery. 

(Photo: Piron Guillaume/Unsplash)

Bennett showed “signs of acceptance” in the days following the transplant, and both researchers and Bennett’s family were optimistic that his health was taking a positive turn. Weeks later, however, Bennett’s lungs began collecting fluid. His blood pressure dropped and he struggled to stay awake. Worst of all, capillaries in the transplanted heart appeared to be leaking, which allowed blood cells into the heart tissue and resulted in severe swelling. Bennett was removed from life support in early March, and the transplant was deemed a failure. 

An autopsy revealed that Bennett’s new heart had doubled in weight prior to his death, mostly as a result of the capillary leaks. Scientists identified “scattered myocyte necrosis,” or the death of heart muscle cells, though the sporadic nature of this complication indicated it wasn’t solely responsible for the failure. The heart’s state was not consistent with typical immune rejection, which would have been apparent if viral (PERV-C) takeover had occurred. With this information, it’s now up to the researchers to investigate the reasons for the heart’s capillary leaks and cell death. 

While at first these appear to constitute a non-answer, they resolve a crucial question regarding immune rejection’s potential part in the transplant’s failure. Up to a of organ transplants fail because of immune rejection; if this wasn’t the core reason for Bennett’s death, researchers might be able to “iron out the kinks” so that future iterations of the procedure are effective long-term. 

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