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Physiology: Restoring cellular functions in pigs after death

Nature

August 4, 2022

A system that can restore some molecular and cellular functions and can preserve tissues in pigs when initiated one hour after death is reported in Nature this week. No evidence of electrical brain activity associated with normal brain function was observed during the procedure. This approach may have the potential to increase organ availability for transplantation, although further research is needed to understand the implications and applications of these findings.

When blood flow ceases in mammals, the lack of oxygen and nutrient circulation triggers a cascade of events that lead to cellular death and organ injury. Methods to preserve tissues and promote recovery have been demonstrated in isolated organs, but scaling up such interventions to the whole-body level has proven challenging. Nenad Sestan and colleagues adapt one such technology — BrainEx, which was shown to restore some function in pig brains hours after death — for whole-body use in large mammals.

The scaled-up system, named OrganEx, is connected to the circulatory system and pumps a fluid containing factors that can counteract the damaging metabolic and electrolyte imbalances that result from blood flow cessation. The authors test the system in pigs one hour after cardiac arrest and compare it with a more traditional system for restoring circulation: an extracorporeal membrane oxygenation system (ECMO). OrganEx is shown to preserve tissue integrity, decrease cell death and restore selected molecular and cellular processes across multiple vital organs (such as the heart, brain, liver and kidneys). Organs treated with OrganEx displayed fewer signs of haemorrhage or tissue swelling than those treated with ECMO. They also observe organ-specific and cell type-specific gene expression patterns that indicate that repair processes are occurring within the body.

Further exploration and development is needed to fully understand the potential of OrganEx to aid cellular recovery after death or interrupted blood circulation, the authors note. The findings highlight a previously unappreciated capacity of the mammalian body to partially recover after an interruption to blood flow, which could increase organ availability for transplantation, the authors conclude.

doi: 10.1038/s41586-022-05016-1

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