August 3, 2022 -- Yale University scientists were able to restore blood circulation and other cellular functions in pigs a full hour after their deaths from cardiac arrest by using technology that delivers a specially designed cell-protective fluid to organs and tissues, according to a paper published August 3 in the journal Nature.
The technology, called OrganEx, includes a perfusion device similar to heart-lung machines and an experimental fluid -- some ingredients are proprietary -- containing compounds that can promote cellular health, decrease the rate of cell death, and suppress inflammation throughout the pig's body.
"Under the microscope, it was difficult to tell the difference between a healthy organ and one which had been treated with OrganEx technology after death," Dr. Zvonimir Vrselja, PhD, an associate research scientist in neuroscience at Yale School of Medicine, said in a statement.
Cardiac arrest was induced in anesthetized pigs, which were treated with OrganEx an hour after death. The scientists found six hours after treatment that certain key cellular functions were active in many areas of the pigs' bodies -- including in the heart, liver, and kidneys -- and that some organ function had been restored, including electrical activity in the heart.
"Single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes," state the authors of the paper. "Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal."
The publication of their latest work -- funded by the U.S. Department of Health & Human Services, National Institutes of Health, and National Institute of Mental Health -- follows 2019 experiments by the researchers in which they revived the disembodied brains of pigs four hours after the animals died. That Yale-led project restored circulation and certain cellular functions in the brain of a dead pig with technology called BrainEx.
In both the 2019 and latest experiments, the scientists found that cellular activity in some areas of the brain had been restored. However, no organized electrical activity that would indicate consciousness or awareness was detected.
While the researchers warn that the findings aren't yet clinically relevant, their work could potentially help extend the health of human organs during surgery and expand availability of donor organs. The technology might also be able to help treat organs or tissue damaged by ischemia during heart attacks or strokes, according to the scientists. It also raises ethical questions about the definition of death.
"There are numerous potential applications of this exciting new technology," said Stephen Latham, PhD, director of the Yale Interdisciplinary Center for Bioethics. "However, we need to maintain careful oversight of all future studies, particularly any that include perfusion of the brain."
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