OrganEx: Scientists restored cell functions in vital organs of dead pigs

Minutes after the heart’s last beat, a sequence of biochemical events, triggered by a lack of blood circulation, oxygen and nutrients, begins to destroy a body’s cells and organs. But scientists in the US have shown that this process does not need to happen so quickly after death.

Researchers have developed a system for delivering oxygen and a specially designed protective fluid that can restore after death some important molecular and cellular functions in various vital organs.

Experiments have shown that it is possible to restore blood circulation and keep tissues functioning in pigs when the recovery process begins within an hour of the animals’ death.

Scientists hope the new method can increase the availability of organs for transplant, as well as help improve the treatment of severe strokes and heart attacks, although further research is needed to explore its potential applications in depth.

When blood circulation stops in humans and other mammals, the lack of oxygen and nutrients triggers a series of processes that lead to cell death and organ damage. Methods for tissue preservation have been developed for individual organs, but until now it has proved very difficult to make such interventions at the level of the whole body.

The researchers, led by neuroscience professor Nenant Sestan of Yale University School of Medicine, who published in the journal Nature, adapted a pre-existing technology of theirs, the BrainEx system developed in 2019, to restore functions of the dead brain. , so that it can now restore after death some functions throughout the body of large mammals such as pigs.

“Not all cells die immediately, there is a more prolonged series of events. It’s a process that you can intervene in, stop it, and restore certain cellular functions,” said neuroscientist Dr. David Andrijevic of Yale.

The new upgraded system called OrganEx connects to the circulatory system and injects into the dead body an experimental liquid (cryoprotective perfusate) containing various substances, which compensate for the destructive metabolic and other imbalances due to the interruption of blood flow. The system was successfully tested on pigs one hour after they died from cardiac arrest.

Six hours later, OrganEx was found to have preserved several tissues intact, reduced cell death, and restored selected molecular and cellular processes in multiple organs, including the heart (which regained electrical activity and contractility), the brain (however, it was not found to be organized its electrical activity that is a sign of consciousness), in the liver, pancreas, kidneys and muscles (especially of the head and neck). Compared to the effectiveness of a more traditional system of oxygenation (Extracorporeal Membrane Oxygenation System-ECMO), organs connected to OrganEx showed less signs of bleeding or tissue swelling.

“Under the microscope it was difficult to tell the difference between a healthy organ and one that had been attached to OrganEx after death,” the researchers reported. However, they stressed that further clinical study and development of the system is necessary to ensure its safety and to fully understand the potential of OrganEx, in terms of cellular regeneration after death or interruption of blood circulation.

Organ donation after death can be distinguished into two categories: after circulatory death or after brain death. In the second case the donors had no brain function, but had intact blood circulation. In the first case, those who become organ donors have severe irreversible brain damage and at the same time are kept alive with respiratory and circulatory mechanical support.

Organs obtained from donors after circulatory death and after the support machinery has ceased to function have been damaged by previous oxygen deprivation, so transplantation of such organs leads to a worse outcome than organs obtained from a donor who suffered brain death. It is therefore important to find a way to post-mortemly restore the function of organs for transplantation, which is what the new OrganEx system promises.

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