Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation DOI Creative Commons
Megan M. Sperry, Berenice Charrez, Haleh Fotowat

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 6, 2024

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening metabolism, mobility, development in Xenopus, we identified an existing drug, SNC80, rapidly reversibly slows biochemical activities while preserving cell tissue viability. Although SNC80 was developed a delta opioid receptor activator, discovered its ability slow metabolism is independent modulating activity novel analog (WB3) almost 1000 times less binding equally active. Metabolic suppression also achieved using microfluidic human organs-on-chips, well explanted whole porcine hearts limbs, demonstrating cross-species relevance this approach potential clinical surgical transplantation. Pharmacological induction combination perfusion transport systems may offer new therapeutic preservation transplantation, trauma management, enhancing patient survival remote low-resource locations.

Language: Английский

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation DOI Creative Commons
Megan M. Sperry, Berenice Charrez, Haleh Fotowat

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 6, 2024

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening metabolism, mobility, development in Xenopus, we identified an existing drug, SNC80, rapidly reversibly slows biochemical activities while preserving cell tissue viability. Although SNC80 was developed a delta opioid receptor activator, discovered its ability slow metabolism is independent modulating activity novel analog (WB3) almost 1000 times less binding equally active. Metabolic suppression also achieved using microfluidic human organs-on-chips, well explanted whole porcine hearts limbs, demonstrating cross-species relevance this approach potential clinical surgical transplantation. Pharmacological induction combination perfusion transport systems may offer new therapeutic preservation transplantation, trauma management, enhancing patient survival remote low-resource locations.

Language: Английский

Citations

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