Organ transplantation can save lives, but unfortunately organs do not have a long shelf life. Scientists have now demonstrated that existing drugs can reprogram donor hearts to last longer outside the body and reduce the risk of post-transplant failure.
Currently, donated hearts can only survive refrigerated for about four hours, so there isn’t much time between donor and recipient. Many of the problems are caused by a molecule called succinic acid. Succinate accumulates in the body while organs are on ice. When blood is then reintroduced into the heart, succinate can cause oxidative stress, causing damage and heart failure, one of the leading causes of premature death in transplant patients.
For a new study, scientists at the University of Michigan investigated how to combat that problem by using itaconate, an enzyme known to neutralize succinate. By scanning, the team identified a drug called valproic acid as a likely source of itaconic acid.
In refrigerated trials on human and pig hearts, valproic acid helped the heart produce antioxidant and anti-inflammatory proteins, which helped relieve stress caused by succinate.
“Using a metabolomics screen, we found that valproic acid can reprogram donor hearts to produce beneficial itaconic acid during storage,” said Paul Tan, senior author of the study. “We have previously shown that the heart is indeed very biologically active while kept on ice, which makes therapeutics useful for protecting it from metabolic stress during this period.” This opens up an opportunity. Not only does this potentially double the amount of time the heart spends in cold storage, but it also reduces the risk of primary graft dysfunction, making transplants even safer. .”
This could significantly improve outcomes for patients requiring heart transplantation. Because organs can travel farther, patients have more time to prepare for surgery. It should also help reduce the number of wasted donor hearts and clear the backlog of waiting-list patients.
“We expect that the overarching principles here can also be applied to preserve other organs such as lungs, livers and kidneys,” said Eugene Chen, co-author of the study. “We expect this treatment strategy to be relevant to other conditions in which the blood supply is interrupted, such as heart attack and stroke.”
And perhaps best of all, valproic acid is already FDA-approved and used to treat seizures. remains.
A study was published in a journal Science Translational Medicine.
Source: University of Michigan
