This string of events had been considered to be unavoidable and irreversible. Now, a new animal study shows that heart death mustn’t necessarily suggest a quick end to the rest of the body.
The researchers restored blood circulation and other cellular functions in the bodies of pigs that had been dead for a full hour, using a new drug cocktail designed to reverse the various catastrophic effects that come with the loss of blood flow.
"Specifically, we restored some functions of cells across multiple vital organs that should have been dead without our intervention," said senior researcher Dr. Nenad Sestan, a professor of neuroscience at Yale School of Medicine in New Haven, Conn. "These cells are functioning hours after they should not be, and what this tells us is that the demise of cells can be halted and their functionality restored in multiple vital organs, even one hour after death."
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The process did not establish the sort of organized electrical activity in the pigs' brains that would provide consciousness. It also did not undo all the organ damage that occurred during that hour of death, the researchers reported Aug. 3 in the journal Nature. But the researchers think their technology would be a huge step forward in preserving individual organs for transplant and expanding the availability of donor organs.
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"Within minutes after the heart stops beating, there is a whole cascade of biochemical events triggered by a lack of blood flow," said co-researcher Dr. Zvonimir Vrselja, an associate research scientist in neuroscience at Yale. "Oxygen and nutrients that the cells need for survival are stopped, and this begins to destroy cells."
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"What we showed is that this progression toward massive permanent cell failure and death does not happen so quickly that it cannot be averted or possibly corrected," Vrselja noted during a Tuesday media briefing.
The technique, called OrganEx, consists of a cocktail of 13 different drugs aimed at reversing most of those events that occur after the heart stops, Vrselja said.
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The cocktail includes anticoagulants to revert the function of blood vessels, drugs that ward off cell death, and anti-inflammatories to limit tissue damage caused by an immune system responding to the body's demise, Vrselja explained.
OrganEx also includes a pumping system meant to restore and maintain blood flow while adding the drug cocktail to the bloodstream.
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"When the heart stops beating, organs begin to swell, collapsing blood vessels and blocking circulation," Vrselja said. "We had to develop a perfusion system that can circumvent that. Basically the whole technology is like ECMO on steroids, allowing us to open blood circulation throughout the whole body."
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For the study, the pigs were sedated and anesthetized and then induced to have fatal cardiac arrest. After an hour at room temperature, they were then placed on the OrganEx system.
Six hours after treatment with OrganEx, researchers discovered that key cellular functions were active in the heart, liver and kidneys of the pigs, and that some organ function had been restored.
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For instance, the heart showed proof of electrical activity and maintained its ability to contract. The researchers also saw organ- and cell-specific gene expression patterns that indicated repair processes underway within the revived body.
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The researchers compared the results of OrganEx against pigs treated with ECMO (extracorporeal membrane oxygenation system). ECMO is used in hospitals to keep blood oxygenated; it's a common lifesaving treatment in severely ill COVID-19 patients.
Organs in pig bodies treated with OrganEx displayed fewer signs of hemorrhage or swelling than those put on ECMO, the results showed.
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