Experiment Restores Cell And Organ Functions to Dead Pigs, Hours After They Died

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.