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• Posted February 9, 2023

Scientists Devise Way to Keep Donor Hearts Viable Longer

Doctors have discovered a way to extend the short shelf life of donor hearts, which could hopefully make more of the organs available to desperate recipients.

Valproic acid (Depakote), which is approved to treat seizures, boosts production of an enzyme that increases the length of time donated hearts can be stored and transported.

The drug also could improve the hearts' function after they are transplanted, according to the study published Feb. 8 in the journal Science Translational Medicine.

Hundreds of thousands of heart failure patients are waiting for a donor heart in the United States, but only around 4,000 heart transplants are conducted each year, the researchers said in background notes.

One reason is that a heart can survive outside a donor body for only about four hours. Further, the longer it takes for the transplant to occur, the more likely that the heart will not work well for its new owner.

About 10% to 20% of heart transplants fail because the new heart is too weak to pump enough blood to supply the rest of the body, the researchers said. That condition is responsible for two out of five early deaths following a heart transplant.

"Being able to extend the storage of hearts by figuring out the pathways that define and modulate preservation biology is the first step toward the ultimate goal of organ banking,"said senior study author Dr. Paul Tang, a heart transplant surgeon at University of Michigan Health, in Ann Arbor.

A substance called succinate is suspected to be a factor in the speed at which hearts go bad during transportation. The harmful molecule accumulates while a heart is on ice and creates a flash of oxidative stress when blood starts flowing through the organ again, causing the heart to malfunction.

To combat this, researchers looked for ways to increase the production of itaconate, an anti-inflammatory and antioxidant that neutralizes the effects of succinate.

The investigators discovered that valproic acid prompts an iced-and-waiting donor heart to produce antioxidants and anti-inflammatory proteins like itaconate. The process worked in both human and pig hearts.

"We found that valproic acid can reprogram the donor heart to produce beneficial itaconate during preservation,"Tang said in a university news release. "We showed previously that hearts are in fact biologically very active while stored on ice, which opens up the therapeutic opportunity to help it protect itself from metabolic stress during this time."

Tang added, "Not only could this possibly double the time a heart could spend in cold storage, but it could reduce the risk of primary graft dysfunction, to make transplant even safer."

The researchers hope that because valproic acid is already approved (to treat seizures), the road to a clinical trial that verifies their findings will be shorter than usual.

"This discovery will buy time to allow a donor heart to reach patients in parts of the country not previously accessible -- greatly impacting the landscape of organ transplant in America,"said study co-author Dr. Eugene Chen, a professor of cardiovascular medicine at the University of Michigan Medical School.

"The overarching principles here can be expected to apply to preservation of other organs, such as lungs, livers and kidneys," Chen added. "I would also anticipate this treatment strategy to be relevant for other conditions where blood supply is disrupted, such as heart attack or stroke."

More information

The Cleveland Clinic has more about organ donation and transplantation.

SOURCE: University of Michigan, news release, Feb. 8, 2023