Beijing time on December 31, according tomedia reports, in the organ transplant surgery, doctors are undoubtedly in a race against time, and often fall in the wind. First, a medical team will remove organs from the donor’s body, which requires the precise cooperation of multiple medical personnel. The doctor then does some processing to remove the removed organs to prepare them for long-distance transportation. Sometimes organs take several hours by air to reach your destination. After that, the transplant can only begin. Doctors must act quickly to ensure patient safety and to ensure that organs are still alive and well.
This description sounds like a plot in a TV series. You may have also seen the tv series of medics running through hospital corridors with organs in cold boxes. This leads us to wonder: How long can organs used for transplantation stay in vitro for as long as possible?
It depends on the organ itself. For the time being, the window period ranges from 4 hours to 36 hours. But doctors hope that one day this period will be extended to a few weeks.
Organs on ice
In 2018, 35,600 organ transplants were performed in the United States alone. So far, the kidneys are the most common transplant, with 21,000 kidney transplants performed last year. This is followed by liver, heart and lung, followed by pancreas, intestines and multi-organ transplants.
When most organs are removed, they are stored in a “static refrigerated” box filled with ice.
“The idea of refrigerated organs is similar to keeping food in a refrigerator, ” said Mingyao Liu, a professor of surgery and dean of the School of Medical Research at the University of Toronto in Canada. “
Before placing the organ in the freezer, the doctor first injects a “preserving liquid” into it to prevent damage to the organ frostbite.
At normal body temperature, the cells pump chemicals into or out of the cell membrane, maintaining a low-sodium, high potassium balance inside the cell. But cells at low temperatures are not able to carry out this process effectively, and chemicals move in and out freely through the cell membrane. Over time, the cells will swell due to too much cell fluid, causing serious damage. The protective fluid temporarily maintains the sodium-potassium balance, delaying cell damage. The protective fluid also contains nutrients and antioxidants that sustain cell survival and inhibit inflammation. Coupled with ice cubes and freezers, the protective fluid keeps the organs safe for hours after they are picked.
When the temperature is between 0 and 4 degrees Celsius, the cell’s metabolism drops to about 5% of normal levels, so tissues consume much more energy and much less oxygen. Therefore, refrigerated organs help delay the time when organs are damaged by lack of oxygen.
Refrigerated organs can also extend the use of organ energy reserves, preventing harmful metabolism and damaging organ tissue, according to a 2019 report.
Brian Lima, director of heart transplant surgery at North Shore University Hospital in New York, points out that in common transplants, the heart is the fastest to live in refrigeration, preferably no more than four to six hours. After 4 hours of cardiac exosome, the function of the heart cells will begin to malfunction, and the probability of not functioning properly after transplantation will greatly increase. Dr Lima said the failure of the transplant was the “most terrible complication” of the transplant.
“The heart is most sensitive to ischemia,” Lima notes. “The removed kidneys maintained 24 to 36 hours of activity under cold storage conditions, longer than the other organs in the top four. James Markmann, director of transplant ation at Massachusetts General Hospital in Boston, adds that the lungs can be kept for six to eight hours and the liver for about 12 hours.
Although the freezer is not technologically charged, it is a “simple and effective way of organ preservation and transportation” and has been widely used since the 1960s. But the technology is not perfect. Refrigerated organ activity lasts only a few hours, and doctors are unable to assess the quality of the organ.
Simply put, as long as the organ is still in the freezer, the doctor cannot objectively test to determine whether the organ is still functioning properly. However, a new alternative technology could allow doctors to check the state of their organs before a transplant, and could soon be adopted on a large scale.
The method, called perfusion preservation, requires the removal of organs to be connected to a special machine that pumps oxygen-rich and nutrient-rich liquids into the organs, just as the heart functions in the human body. When connected to the machine, the organ can still normally metabolize energy and produce waste, while the organ’s sugar reserve can be replenished and toxic metabolites can be removed in time.
The donor’s heart has stopped supplying blood to the organ for some time before the doctor removes the organ, which can cause damage to the organ. At this point, if the organ is connected to the perfusion machine in time, it may give organ tissue a chance to recover. In addition, doctors can check organ status through metabolic lactate levels circulating in the monitoring system. Cells consume lactic acid when carrying out normal metabolic functions. So if the organ functions properly, there will be no excess lactic acid in the tissue.
Dr. Lima points out that while the use of lactic acid to assess the effects of organ perfusion is simple and crude, it is undoubtedly better than the traditional method of judging organ status by visual inspection. In addition, doctors can use different assessment methods for different organs, such as analyzing the liver’s bile secretion capacity, and so on.
Can perfusion preservation extend organ preservation time?
Some perfusion systems still need to keep organs in cold, but over the past 20 years, several research teams have tried to keep the organs warm and fill them with room-temperature blood. At temperatures between 20 and 33 degrees, the exosome organs still function basically. Today, cryogenic and room temperature perfusion preservation systems are widely used in Australia and the United Kingdom, but are still largely in clinical trials in the United States.
However, the perfusion preservation system used in a heart transplant at Duke University Medical Center in the United States in December has raised concerns. Doctors removed the donor’s heart after it stopped, and then used a room-temperature perfusion system to “bring the heart back to life.” In this type of surgery, doctors remove a donor who has already died of brain power before the heart stops to prevent damage to the heart muscle hypoxia. U.S. doctors have previously “resuscitated” a child’s heart, but it is the first time an adult heart has been resuscitated. In countries where the system has been in place for several years, the number of transplant-eligible hearts has increased by 30 to 40 percent. If it goes to the United States, it would be an incredibly large number.
Jacob Schroder, an assistant professor of surgery at Duke University and one of the participants in the heart transplant, said that if the system were adopted nationwide, “the number of potential donors and heart transplants would increase by 30 percent.”
The question is, the number of donors may increase, but can the condition of the organs improve? Few studies have directly compared the refrigeration preservation method with the perfusion preservation method, but organs that are said to have been preserved by perfusion method appear to be in better condition.
For example, in a clinical trial comparing the two methods, doctors rejected 32 livers that had been preserved by standard refrigeration method, but only 16 livers saved by perfusion because the latter was less damaged. Dr. Liu mingyao said he had observed a similar trend in the lung transplants he had undergone. Liu Mingyao and his colleagues developed a “lung in vitro perfusion system”. Prior to the introduction of the system, they had a lung transplant success rate of less than 20 per cent in hospitals. Today, the system’s usage has increased by 70 per cent and is “very effective”.
The removal of the lungs and the irrigation system is usually connected between 4 and 6 hours. But experiments with animal organs showed that the lungs after perfusion could remain active for 12 to 18 hours, up to a maximum of 36 hours. Sooner or later, Dr. Liu added, the deadline could be extended to several weeks. The longer the organ is removed, the more laborious it will be to repair the damaged tissue. Liu Mingyao and his colleagues are working on ways to prevent inflammation of the lungs and cell death after infusion. He points out that in the future organs, when connected to the perfusion system, they may be treated with genetic or stem cell therapies.
For now, however, most donated organs are still transported by means of cold storage and ice. Why is that?
“To be honest, the main obstacle to perfusion preservation is cost. Dr. Lima pointed out. Each organ’s perfusion system costs thousands of dollars, far exceeding the price of a standard refrigerator. Coupled with the direct comparison of the two methods of research is not much, there is no “undoubted” data, not enough to convince the major hospitals.
But given the recent success of heart transplants at Duke University Medical Center, perfusion preservation may soon become the standard method of organ transportation.