HANDOUT - OrganEx technology reverses certain deleterious effects of prolonged ischemia. Representative images of electrocardiogram tracings in the heart(top), immunostainings for albumin in the liver(middle),and actin in the kidney(bottom).The images on the left side represent the organs subjected to a control perfusion, while the images on the right represents the organs subjected to perfusion with theOrganEx technology. Tissue integrity and certain cellular functions have been restored by theOrganEx technology one hour after circulatory arrest. Image credit: David Andrijevic, Zvonimir Vrselja, Taras Lysyy, Shupei Zhang; Sestan Laboratory; Yale School of Medicine ACHTUNG: Frei nur zur redaktionellen Verwendung im Zusammenhang mit der Berichterstattung über die Studie bei Nennung des Credits. Foto: David Andrijevic, Zvonimir Vrselja, Taras Lysyy, Shupei Zhang; Sestan Laboratory; Yale School of Medicine

A study in pigs raises questions about the line between life and death: US researchers used a special perfusion system – called OrganEx – to restore some cell and organ functions to pigs that had been dead for an hour. This is reported by a team from Yale University in the journal “Nature”.

“Even under the microscope, it was difficult to distinguish a healthy organ from one that had been treated with OrganEx after death,” co-author Zvonimir Vrselja is quoted as saying in a statement from the university. “These latest results raise a lot of questions – not the least of which is whether the medical and biological determination of death needs revision,” writes Brendan Parent of New York University in a Nature commentary.

What is it about? If mammalian cells are cut off from the supply of oxygen, a cascade of diverse decay processes sets in, at the end of which cells, organs and sometimes even the entire organism die off. However, it is questionable how long it will take for irreversible damage to occur.

The Yale team led by neuroscientist Nenad Sestan raised this question three years ago. At that time, the team restored some cell activity in the brains of pigs that had been slaughtered about four hours previously.

At that time, they pumped a special solution through the main arteries of the heads with a specially developed machine and discovered six hours later that some cell functions were still intact – such as nerve cell activities, metabolic activities or reactions of the blood vessels to drugs, for example.

This is where the current study comes in, which goes far beyond that of the time: “If we were able to restore certain cell functions in the dead brain – the organ known to be most sensitive to ischemia – we assumed that something similar would also be possible in other vital organs would be possible,” explains Sestan.

The team tested this on pigs after cardiac arrest. One hour after death, the researchers connected the animals’ circulation to the OrganEx machine. This pumped a mixture of the animals’ blood and a special liquid into the circulatory system for six hours according to a special pattern.

This perfusate contained a good dozen special components, including anti-clotting agents, anti-inflammatory agents, anti-immune agents, and anti-cell death agents. “We were able to restore circulation throughout the body, which amazed us,” sums up Sestan.

The team then registered restored cell and sometimes even organ functions in a number of organs such as the heart, liver and kidneys – such as the heart’s ability to contract. Analyzes of gene expression indicated that repair processes were taking place in the body.

The researchers even registered complex movements of the torso, neck and head across multiple joints and muscle units. This points to the preservation of some motor functions. As in 2019, the team also found cell activity in the brain, but no evidence of electrical activity or even consciousness.

“Overall, further optimization and extension of our technology is required to fully understand its broader implications for hypoperfused tissues,” the team writes.

The researchers emphasize that this applies in particular to the regeneration of some brain functions and also refers to the previously unexplained movements of the neck and head. The technology is very promising, but still a long way from being used in humans, the scientists emphasized at a press conference on Tuesday afternoon.

“This comprehensive and well-planned study has the potential to open up new treatment strategies for people who have had a heart attack or stroke,” writes Robert Porte of the University Hospital Groningen in a “Nature” comment.

“It is conceivable that the OrganEx system (or components thereof) could be used to treat such people in an emergency.” Before doing so, however, the security of the procedure must be clarified, but the most important thing is the system for organ donation.

Jan Gummert from the Heart and Diabetes Center NRW in Bad Oeynhausen speaks of a very exciting study. “Should the data be corroborated, then use in transplantation medicine would definitely be conceivable,” says the director of the Clinic for Thoracic and Cardiovascular Surgery.