Prolyl hydroxylase domain inhibitor: a potential pre-hospital pharmaceutical intervention for trauma and hemorrhagic shock Article Swipe
Xiaowu Wu
,
P. Andrew
,
James A. Bynum
,
Tiffani C. Chance
,
Daniel N. Darlington
,
Michael A. Meledeo
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3411470/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3411470/v1
Trauma and hemorrhagic shock-associated pre-hospital deaths are mainly due to hypoperfusion-induced tissue hypoxia leading to irreversible organ dysfunction at or near the point of injury or during transportation prior to receiving definitive therapy. The prolyl hydroxylase domain (PHD) is an oxygen sensor that regulates tissue adaptation to hypoxia by stabilizing hypoxia inducible factor (HIF). The benefit of PHD inhibitors (PHDi) in the treatment of anemia and lactatemia arises from HIF stabilization, which stimulates endogenous production of erythropoietin and activates lactate recycling through gluconeogenesis. The results of this study provide insight into the therapeutic roles of MK-8617, a pan-inhibitor of PHD-1, 2, and 3, in the mitigation of lactatemia in anesthetized rats with polytrauma and hemorrhagic shock. Additionally, in an anesthetized rat model of lethal decompensated hemorrhagic shock (65% of estimated blood volume (EBV)), acute administration of MK-8617 significantly improves one-hour survival and maintains survival at least until 4 hours following limited resuscitation with whole blood (20% EBV) at one hour after hemorrhage. This study suggests that pharmaceutical interventions to inhibit prolyl hydroxylase activity can be used as a potential pre-hospital countermeasure for trauma and hemorrhage at or near the point of injury.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3411470/v1
- https://www.researchsquare.com/article/rs-3411470/latest.pdf
- OA Status
- green
- References
- 64
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4387701235
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4387701235Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3411470/v1Digital Object Identifier
- Title
-
Prolyl hydroxylase domain inhibitor: a potential pre-hospital pharmaceutical intervention for trauma and hemorrhagic shockWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-10-16Full publication date if available
- Authors
-
Xiaowu Wu, P. Andrew, James A. Bynum, Tiffani C. Chance, Daniel N. Darlington, Michael A. MeledeoList of authors in order
- Landing page
-
https://doi.org/10.21203/rs.3.rs-3411470/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3411470/latest.pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
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https://www.researchsquare.com/article/rs-3411470/latest.pdfDirect OA link when available
- Concepts
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Medicine, Hemorrhagic shock, Hypoxia (environmental), Shock (circulatory), Resuscitation, Polytrauma, Pharmacology, Blood volume, Anesthesia, Internal medicine, Surgery, Chemistry, Organic chemistry, OxygenTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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64Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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