Mayo Clinic researchers have identified a breakthrough approach that could dramatically extend the preservation time for donor hearts, potentially making more organs available for life-saving transplants. The discovery, published May 19 in Nature Cardiovascular Research, reveals how an existing cardiac medication can nearly triple donor heart function during extended cold storage.
Protein Clumping Damages Hearts During Storage
The research team, led by Dr. Paul Tang, a cardiac surgeon at Mayo Clinic in Rochester, Minnesota, focused on understanding why donor hearts deteriorate during cold storage transport. They discovered that mineralocorticoid receptor proteins within heart cells undergo a process called liquid-liquid phase separation, causing them to clump together in ways that harm cardiac tissue.
"This process promotes cardiac damage from increased inflammation and cell death, making the heart less likely to function well after transplant," the researchers explained. The protein aggregation occurs specifically during the cold storage conditions used to preserve organs during transport from donor to recipient.
Canrenone Treatment Shows Dramatic Results
To test whether this damaging process could be prevented, researchers treated donor hearts with canrenone, a drug that blocks mineralocorticoid receptor activity and is already approved for treating heart conditions. The results were striking: treated hearts showed nearly triple the pumping strength compared to untreated hearts stored under the same conditions.
Beyond improved cardiac output, the canrenone-treated hearts demonstrated better blood flow and significantly reduced signs of cellular injury. These improvements occurred even when hearts were stored beyond the typical timeframe considered safe for transplantation.
"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," Tang said. "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."
Addressing Critical Organ Shortage
The findings address a significant challenge in cardiac transplantation: currently fewer than half of donated hearts are ultimately used for transplant. One major limiting factor is the relatively short window for successful transplantation due to concerns about functional deterioration during cold storage.
Up to 20% of heart recipients experience primary graft dysfunction, a serious complication where the transplanted heart cannot pump blood effectively following surgery. This condition is often linked to damage sustained during the preservation period between organ procurement and transplantation.
Broader Implications for Organ Preservation
The research has implications extending beyond cardiac transplantation. The study authors noted that similar protein clumping occurs in other donated organs including kidneys, lungs, and livers during cold storage. This suggests that canrenone treatment could potentially improve preservation outcomes across multiple organ systems.
The collaboration between Mayo Clinic and University of Michigan researchers represents a significant step toward addressing the critical shortage of viable organs for transplantation. By extending safe storage periods, the approach could increase the geographic range for organ matching and provide more time for complex surgical preparations.
The discovery builds on existing knowledge of mineralocorticoid receptor function while revealing a previously unknown mechanism of cold storage injury. Since canrenone is already approved for clinical use, the pathway to implementing this preservation strategy could be more straightforward than developing entirely new compounds.
