Blood in animals provides oxygen and nutrients to the organs and cells of
the body. However, if blood supply is interrupted, these cells soon perish
and organs are damaged.
Organ and tissue removal from the body can delay this demise and buy time
for organ transplantation. However, it might be difficult to keep whole
organ systems alive after the heart stops beating.
The extracorporeal membrane oxygenation system (ECMO), which pumps blood
into a device that removes carbon dioxide from it while supplying oxygen, is
one of the existing treatment options. Although it balances gases, each
minute of delay permits the harm to increase.
In order to solve the issue, it has been demonstrated that a novel approach
may maintain the tissues of dead pigs and recover some organ, cellular, and
molecular function even when the therapy is started only one hour after
cardiac arrest.
The scientists modified a currently used procedure dubbed BrainEx, which
has been demonstrated to partially restore function in isolated pig brains
hours after death.
OrganEx, a brand-new technology, is designed for whole-body use in big
mammals.
The two parts of OrganEx are a machine and a fluid.
The circulatory system is linked to the machine. Similar to an ECMO, it
produces a pulse that is like a heartbeat and oxygenates the fluid. The way
it incorporates medications to promote circulation and avoid clotting is
what makes it unique.
A variety of sensors for crucial aspects of circulation, such as
metabolism, hemoglobin, pressure, and flow, are also included into the
device.
It circulates artificial fluid throughout the whole body of the deceased
animal while blending it 1:1 with its own blood. Although it is intended to
deliver oxygen and medications throughout the body and protect cells from
injury, this fluid, unlike blood, does not contain any cells.
Above: Illustrations of electrocardiogram (ECG) tracings in the heart,
albumin immunostainings in the liver, and actin immunostainings in the
kidney (bottom). The organs treated to a control perfusion are shown in the
photos on the left, while the organs exposed to perfusion using the OrganEx
technology are shown in the images on the right.
Pigs were used as test subjects, and the system was put to the test one
hour after cardiac arrest, as well as in control groups where organ
performance was assessed immediately following the loss of blood flow, one
hour later, and seven hours later. Tissues continued to digest fuel and
produce waste at a regulated rate while being kept at body
temperature.
Overall, 100 pigs (Susscrofa domesticus) were employed, including those
that helped create the system before the studies that were published.
The scientists discovered that in key organs including the heart, brain,
liver, and kidneys, OrganEx may resuscitate certain molecular and cellular
processes, retain the integrity of tissue, and minimize cell death.
Overall, OrganEx performed better than ECMO. Researchers saw reduced tissue
swelling or bleeding in organs treated by the novel approach, and they also
saw gene expression patterns unique to healing processes in certain organs
and cell types.
The scientists also examined the architecture of brain cells, which are
typically damaged by ischemia.
All treatment groups' brain cell counts had decreased, with the exception
of OrganEx, where there had been little brain damage in some areas and a
recovery of prefrontal cortex cells to levels comparable to the control
group.
The restoration of organ function served as a key indicator of the
experiment's success.
Continuous EEG was used to monitor brain activity. The researchers were
adamant about making a distinction between the electrical activity that
might suggest some form of "life" and the brain processes they had
discovered (as brain death is the main definition of death in clinical
settings).
While brain death remained in the OrganEx group, the corpses displayed some
head and neck movement following contrast injection into the neck's carotid
artery, which carries blood to the head and brain. Neither the ECMO group
nor the awake, sedated animals experienced this movement.
The researchers state that "thoughtful examination is needed to explain why
head and neck movements occurred following contrast injection solely in the
OrganEx group."
Although they do not know why this happened, they claim that it
demonstrates that motor function output had been retained, at least in the
"spinal cervical cord or its roots."
ECG was used to identify some spontaneous activity in the heart, and the
OrganEx group showed some left ventricular cell contractions that the ECMO
group did not.
Other organs, including the liver and kidneys, also shown important
evidence of functional improvement.
OrganEx is yet to be tested in people, but the researchers are optimistic
about its enormous potential for organ transplants. They anticipate that
this will increase the amount of time an organ may be stored for transplant,
which could, for example, enable organs to be delivered farther to
recipients who are in need.
The researchers conclude that their findings "highlight a hitherto
underappreciated potential of the mammalian body to partially recover after
an interruption to blood flow, which might boost organ availability for
transplantation."
To fully comprehend the potential of OrganEx to promote cellular repair
after death or halted blood circulation, the team notes that more research
is necessary.
The research was published in
Nature.