ROCHESTER, Minn. — A new discovery by Mayo Clinic researchers could mean more donor hearts are available for heart transplant, giving more people a second chance at life.

In findings published in Nature Cardiovascular Research, a team led by Mayo Clinic cardiac surgeon Paul Tang, M.D., Ph.D., identified a biological process that contributes to donor heart injury during cold storage. The researchers found that a drug already used to treat heart conditions can prevent this damage.

Heart transplantation is the most effective treatment for end-stage heart failure, yet fewer than half of donor hearts are ultimately used. One major reason is the relatively short window for transplanting a donated heart into a patient, due to concerns over low donor heart function that comes from leaving a heart in cold storage too long.  

Why donor hearts deteriorate in cold storage

Although cold storage slows metabolism and helps preserve tissue, prolonged exposure to cold storage conditions can lead to molecular changes that compromise how well the heart performs after transplant. One complication is called primary graft dysfunction, in which the transplanted heart cannot pump blood effectively after surgery. This may affect up to 20% of recipients to varying degrees.

To investigate why this damage occurs, the researchers focused on a protein inside heart cells called the mineralocorticoid receptor, which plays a role in how cells respond to stress. During cold storage, they found that this protein undergoes a process in which the protein clumps together in a way that harms the heart cells, called liquid-liquid phase separation. This process promotes cardiac damage from increased inflammation and cell death, making the heart less likely to function well after transplant.

Preventing damage with a common drug

To test whether the process could be prevented, the researchers treated donor hearts with a drug called canrenone, which blocks mineralocorticoid receptor activity. In human donor hearts stored beyond the typical timeframe, treatment with the drug nearly tripled their pumping strength compared to hearts stored without it. The hearts also showed better blood flow and fewer signs of cell injury. The findings suggest canrenone may help extend the safe storage period for donor hearts by improving the heart’s pumping strength to increase chances of a successful transplant.

"As a cardiovascular surgeon, I’ve personally experienced in the operating room how every additional hour of preservation can impact the likelihood of whether a donor heart can return to normal function after transplantation," Dr. Tang says. "This discovery may give us a new tool to preserve heart function for longer during storage, improve transplant outcomes and enhance patient access to lifesaving transplants."

The study's findings also have the potential to improve the preservation of other transplantable organs. Similar protein clustering was observed in donor kidneys, lungs and livers during cold storage. This suggests that the same strategy may help expand transplant options across multiple organ systems.

Mayo Clinic collaborated with the University of Michigan on this research. Review the study for a complete list of authors, disclosures and funding. 

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About Mayo Clinic 
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Media contact:  

• Susan Murphy, Mayo Clinic Communications, newsbureau@mayo.edu 

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