ArticleThe Journal of surgical research2015
Hypothermia and valproic acid activate prosurvival pathways after hemorrhage.
Article in The Journal of surgical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Systematic review and meta-analysis of experimental studies evaluating the organ protective effects of histone deacetylase inhibitors.Translational research : the journal of laboratory and clinical medicine · 2019Pooled it
- Histone Deacetylase Inhibitors: A Novel Strategy for Neuroprotection and Cardioprotection Following Ischemia/Reperfusion Injury.Journal of the American Heart Association · 2020Review
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.The journal of trauma and acute care surgery · 2018Article
- Pharmacological Intervention of Post-traumatic Seizure: Advanced Research Progress.Dose-response : a publication of International Hormesis SocietyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
backgroundTherapeutic hypothermia (hypo) and valproic acid (VPA, a histone deacetylase inhibitor) have independently been shown to be protective in models of trauma and hemorrhagic shock but require logistically challenging doses to be effective. Theoretically, combined treatment may further enhance effectiveness, allowing us to use lower doses of each modality. The aim of this study was to determine whether a combination of mild hypo and VPA treatments would offer better cytoprotection compared with that of individual treatments in a hemorrhage model. MATERIALS AND
methodsMale Sprague-Dawley rats were subjected to 40% volume-controlled hemorrhage, kept in shock for 30 min, and assigned to one of the following treatment groups: normothermia (36°C-37°C), hypo (30 ± 2°C), normothermia + VPA (300 mg/kg), and hypo + VPA (n = 5 per group). After 3 h of observation, the animals were sacrificed, liver tissue was harvested and subjected to whole cell lysis, and levels of key proteins in the prosurvival Akt pathway were measured using Western blot.
resultsActivation of the proapoptotic protein cleaved caspase-3 was significantly lower in the combined treatment group relative to normothermia (P < 0.05). Levels of the prosurvival Bcl-2 was significantly higher in the combined treatment group relative to sham, normothermia, and normothermia + VPA groups (P < 0.005). The downstream prosurvival protein phospho-GSK-3β was significantly higher in the sham, hypo, and combined treatment groups compared with that in normothermia groups with or without VPA (P < 0.05). Levels of the prosurvival β-catenin were significantly higher in the combined treatment group relative to normothermia (P < 0.01).
conclusionsThis is the first in vivo study to demonstrate that combined treatment with VPA and hypo offers better cytoprotection than these treatments given independently.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.