They manage to 'resurrect' dead organs to buy time for transplants

• Neuroscience 'Resurrect' the brain of 32 pigs that had been dead for more than four hours

Oxygenated blood bathes each and every cell in the body.

The moment the heart stops pumping, the process of tissue destruction begins, ultimately leading to death.

But this is not immediate (Max, the Miraculous said well that "it is not the same to be

dead as totally dead").

For decades,

and ends with irrecoverable organ loss.

Current reperfusion systems manage to cushion this damage, so that the organs removed for a transplant are preserved in better conditions and for longer, but they still have many limitations.

In a curious experiment, published today in the journal

, a team of scientists from Yale University has taken this technology to a higher level,

and many of the cellular functions lost by lack of oxygen in pigs that had been dead for an hour, after a cardiac arrest.

The person in charge of this research, Nenad Sestan, from the Yale Department of Neuroscience, described it this way at a press conference: "It is a perfusion technology that

that would be dead without this intervention. Specifically, we have restored functions that affect multiple vital organs."

Research background: pig brains

Sestan leads the team of neuroscientists who in 2019 first devised this reperfusion system and applied it in an experiment with pig brains.

They then showed that his system, which they called

could

.

After publishing that experiment, which went around the world, many medical colleagues involved in the field of transplantation "knocked on our door", Sestan commented, intrigued by whether tissue repair of such a caliber could be reproduced in other organs.

"That's what prompted us to extend the device to the entire body."

To do this

the result is

a reperfusion machine that has been measured face to face with the current system to restore circulation, the ECMO (from the acronym in English, extracorporeal membrane oxygenation; a circulatory system extracorporeal).

The experimental device has far outperformed the comparison.

Another of the researchers in this work, also a neuroscientist David Andrijevic, has pointed out that

: a

that is pumped into the body, with factors that promote cell repair and stop cell deterioration at different levels.

Part of the success of the experiment, the scientists believe, is due to the sum of these factors and specifically to

.

The

, administered under hypothermic conditions, is an optimization of the one used in the brains experiment.

Without going into too much detail about its ingredients, Zvonimir Vrselja, also the author of the study,

(which allows the transport of oxygen to cells) and

already known for their antiapoptotic, anti-inflammatory, immunomodulatory, anti-inflammatory and coagulation regulator.

The experiment was carried out on

(plus another to which nothing was done), to which they induced cardiac arrest.

They waited an hour and were attached to the two reperfusion devices for another six hours.

After that time, the ECMO was no longer able to restore functionality in the cells or prevent the collapse of many capillaries, while

Looking closely at the animals, the scientists say it was even difficult to distinguish recovered organs from healthy ones under a microscope.

They also verified that the expression of genes involved in cell death and inflammation regulation functions was maintained.

Applications in transplantation and ischemia

Likewise, it showed that part of the functionality could

.

Electrical activity was observed in the heart, which would allow contraction, and the presence of key proteins such as actin in the kidney and albumin in the liver was observed.

The study further shows that organs had fewer signs of bleeding or inflammation with

than with ECMO.

As happened with the experiment in the brains of 2019,

(with signs of consciousness or perception), but that functional restoration is maintained at a normal level. cell in the brain.

"No electrical activity was recorded in the brain of the animals," said the person in charge of the bioethical design of this study, Stephen Latham, of the Yale Interdisciplinary Center for Bioethics.

Sestan has pointed out that the cells work hours after they shouldn't.

"

, even one hour after death, induced by cardiac arrest in this study. The results open the door to future studies in transplantation and possible treatments. "

for ischemic damage.

However, the authors believe that they are still far from the device being applied in the clinical setting.

"

," Latham said, "

."

Donation in asystole

Of special interest would be this development for the

country that leads the global activity in donation in asystole (in cardiorespiratory arrest).

Unlike donation in brain death -the majority in the world- in which the organs are adequately perfused and do not suffer the effect of the lack of oxygenation,

(it can be due to sudden cardiac arrest and in which resuscitation is unsuccessful; or, much more commonly, that this arrest occurs due to catastrophic brain damage or similar pathologies that depend on life support measures, after the decision to withdraw them due to medical futility ).

In asystolic donation,

by stopping receiving oxygenated blood, the organs begin to rapidly lose viability.

Technically, it is a more complicated process than brain death donation.

and, where appropriate, techniques are applied that minimize cell damage caused by ischemia.

To achieve this,

(in which the organs are quickly cooled by infusing preservation fluid) and, pioneered in Spain, normothermic regional perfusion, which is performed by applying ECMO in regions of the body (abdominal cavity, chest).

This technique has become widespread due to its good results, until it is used in almost 70% of cases of donation in asystole.

Thanks to the

, widely used in Spain, it has been possible to increase the

, but also of the organs most vulnerable to the effect of warm ischemia, such as the liver and the heart, and the latter "is an achievement that seemed like science fiction. We are even in the process of applying it to intestinal transplantation."

The results of the experiment are very striking and hopeful,

.

She recalls that in a donation in asystole, after cardiorespiratory arrest and the five minutes legally stipulated in Spain to certify death, reperfusion techniques are started, but the organs have already been suffering from significant hypoperfusion for some time.

"In total,

. Beyond that time, we don't start organ perfusion, even using ECMO (which is connected, depending on the case, from two to, at most, four hours.) In this

by keeping the animals in cardiac arrest for one hour without performing any intervention".

The results show, in the opinion of this specialist, "that with respect to what was achieved with the ECMO system,

", either by being able to exceed a certain ischemia time or by achieving a better recovery of the graft," so that better results would be obtained. That is without assessing its potential in other fields, such as the treatment of patients suffering from an ischemic stroke or a myocardial infarction. Its potential is impressive".

The boost that would come from making such an advance in the clinic is well understood with the figures for transplant activity.

.

Thanks to these 8,166 non-heart beating donors, 18,291 transplants could be performed, according to data provided by the ONT.

The bet made by this type of donation in Spain is now being imitated in other countries around us, and recently in the United States.

In a study of which Domínguez-Gil is the first author -cited in the documentation provided by

on this work- the need to promote this type of donation in other countries is established, something that the European Council has also recently recalled.

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• rafael matesanz