Advances in preservation technology could provide more hearts for transplant surgery. Researchers at the University of Michigan have used a technique called "NEHP" to extend the preservation time of the heart to more than 24 hours, which is expected to extend the transplant window and increase the use of donor hearts.
More than 50 years have passed since the first person-to-person heart transplant, and more than 5,000 heart transplants are now performed worldwide each year. However, this number falls far short of the need, as as many as 50,000 people could need transplants at any one time. Depending on the severity of the patient's condition and various physiological and logistical factors, the waiting time for a transplant can be up to several years. A major limiting factor in meeting this need is the scarcity of suitable donor hearts, in part because of the very short window of time for transplantation once the heart is removed from the deceased donor's body.
The current "gold standard" for preserving a donated heart is cryostatic preservation (CSS), which is keeping the heart on ice before transplantation. Transplantation is most successful when the cold static storage lasts less than 6 hours before the heart or its blood vessels are damaged. Sometimes it can be up to 12 hours, but several days of mechanical life support for the recipient, such as extracorporeal membrane oxygenation (ECMO), are required. Therefore, extending the storage time to more than 6 hours without the need for ECMO would be a medical breakthrough.
Now, researchers published in the journal Frontiers in Cardiovascular Medicine have found that transplanted pig hearts can survive outside the body for more than 24 hours using a method called room temperature external cardiac perfusion (NEHP).
Dr. Robert Bartlett, director of the Extracorporeal Life Support Laboratory and professor emeritus at the University of Michigan Ann Arbor School of Medicine, said, "If applied to humans, this would be a significant improvement over the six-hour time window in standard clinical practice. "
NEHP refers to the removal of the heart from the donor's body by pumping an oxygen- and nutrient-rich fluid ("perfusion") extracted from the plasma to keep the heart partially physiological at room temperature until transplantation. Drugs and tissue repair stem cells can be delivered to the heart through perfusion. Currently, the only NEHP variant approved by the FDA for clinical use is Transmedics-OCS, which, like CSS, is limited to 6 hours of use.
For the past seven years, the Extracorporeal Life Support Laboratory has been working to steadily extend the shelf life of donated hearts by improving NEHP. Their previous experiments have shown that a critical step is to filter the perfusate, removing all molecules smaller than 26 thousand daltons. If this is not done, the heart will soon become unavailable for transplantation for unknown reasons.
Here, Bartlett and his colleagues used an experimental variant, NEHP, to keep the hearts of 30 immature pigs and 10 young pigs alive at different times. For example, the perfusate of all donor hearts is a solution consisting of plasma and packaged red blood cells (from other healthy pigs), electrolytes, glucose, and antibiotics. The perfusate is pumped into the heart at an average rate of 0.7 milliliters per minute per gram of heart weight and is changed every 60 minutes.
They then compared the effects of three variants: NEHP (10 immature hearts) that continuously purified the perfusion and removed toxins through blood filtration, NEHP (5 immature hearts) that continuously exchanged plasma components in the perfusion, and control NEHP (15 immature hearts) without any changes.
To test these methods on larger hearts, they also used NEPH with hemofiltration on the hearts of five young pigs and additionally modified NEPH (intermittent left atrial perfusion or iLA) on the hearts of seven other young piglets to monitor heart function. In iLA, a certain amount of blood is injected into the left atrium at regular intervals to test its ability to continuously spurt blood.
The authors monitored the health of the preserved heart in real time by visually measuring the heart's contractility, rhythm, color, and edema, as well as measuring the concentration of lactate, a byproduct of cell damage, hourly. Each heart is preserved for at least two hours until it stops beating or has an arrhythmia, has a very low left ventricular systolic blood pressure, or has an elevated lactate concentration.
All control hearts died within 10 to 24 hours of removal from the donor, while all hearts saved after modifications to standard NEPH survived for 24 hours. The authors conclude that hemofiltration, plasmapheresis, and iLA are all major improvements, allowing the heart to be routinely preserved for more than a day. As for which of the last three methods is better, there is no answer yet.
"I think the main difference is that when we extend the duration of the experiment to more than 24 hours, maybe plasmapheresis will be better because more toxins can be removed," Bartlett said. iLA also appears to be a significant improvement because, in principle, it allows NEPH to be used in hearts that are traumatized or donor function is on the verge of it. "
"This work can ultimately increase the number of donors. First of all, by extending the storage period, we are able to overcome the limitations caused by logistics. Second, by objectively assessing the viability of each potential donor's heart, reduce the number of hearts that are currently unused when it is unclear how well the heart is functioning in the donor's body," said Dr. Álvaro Rojas Pena, a researcher at the same institute and corresponding author of the study.
"The main challenge for clinical applications is to validate these methods in humans. "To that end, we have started using human hearts that have been rejected for transplantation. "
编译自/scitechdaily