ArticleShock (Augusta, Ga.)2014
Creating a prosurvival phenotype through a histone deacetylase inhibitor in a lethal two-hit model.
Article in Shock (Augusta, Ga.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
20 citing papers in PubMed, 36 citations in OpenAlex.
- Valproic acid for treatment of traumatic brain injury: Study protocol for the VIBRANT prospective randomized trial.Transfusion · 2026Article
- Single-cell multi-omics-based immune temporal network resolution in sepsis: unravelling molecular mechanisms and precise therapeutic targets.Frontiers in immunology · 2025Review
- Epigenetic regulation of pulmonary inflammation.Seminars in cell & developmental biology · 2024Review
- [A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
- Effect of valproic acid upon skeletal muscle subjected to prolonged tourniquet application.Trauma surgery & acute care open · 2023Article
- Pretreatment with valproic acid alleviates pulmonary fibrosis through epithelial-mesenchymal transition inhibition in vitro and in vivo.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Spatiotemporal evaluation of the mouse embryonic redox environment and histiotrophic nutrition following treatment with valproic acid and 1,2-dithiole-3-thione during early organogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Histone Deacetylase Inhibitors: A Novel Strategy in Trauma and Sepsis.Shock (Augusta, Ga.) · 2019Review
- Valproic acid improves survival and decreases resuscitation requirements in a swine model of prolonged damage control resuscitation.The journal of trauma and acute care surgery · 2019Article
- Epigenetics in Sepsis: Understanding Its Role in Endothelial Dysfunction, Immunosuppression, and Potential Therapeutics.Frontiers in immunology · 2019Review
- Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock.Trauma surgery & acute care open · 2019Article
- Protective Effect of Tubastatin A in CLP-Induced Lethal Sepsis.Inflammation · 2018Article
- Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.The journal of trauma and acute care surgery · 2018Article
- Different resuscitation strategies and novel pharmacologic treatment with valproic acid in traumatic brain injury.Journal of neuroscience research · 2018Review
- Trauma care: Finding a better way.PLoS medicine · 2017Article
- Selective inhibition of histone deacetylase 6 promotes survival in a rat model of hemorrhagic shock.The journal of trauma and acute care surgery · 2015Article
- Creating a "Prosurvival Phenotype" Through Histone Deacetylase Inhibition: Past, Present, and Future.Shock (Augusta, Ga.) · 2015Review
- Selective histone deacetylase 6 inhibition prolongs survival in a lethal two-hit model.The Journal of surgical research · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
objectivesHemorrhagic shock (HS) can initiate an exaggerated systemic inflammatory response and multiple organ failure, especially if followed by a subsequent inflammatory insult ("second hit"). We have recently shown that histone deacetylase inhibitors can improve survival in rodent models of HS or septic shock, individually. In the present study, we examined whether valproic acid (VPA), a histone deacetylase inhibitor, could prolong survival in a rodent "two-hit" model: HS followed by septic shock from cecal ligation and puncture (CLP).
methodsMale Sprague-Dawley rats (250-300 g) were subjected to sublethal HS (40% blood loss) and then randomly divided into two groups (n = 7/group): VPA and control. The VPA group was treated intraperitoneally with VPA (300 mg/kg in normal saline [NS], volume = 750 μL/kg). The control group was injected with 750 μL/kg NS. After 24 h, all rats received CLP followed immediately by injection of the same dose of VPA (VPA group) or NS (vehicle group). Survival was monitored for 10 days. In a parallel study, serum and peritoneal irrigation fluid from VPA- or vehicle-treated rats were collected 3, 6, and 24 h after CLP, and enzyme-linked immunosorbent assay was performed to analyze myeloperoxidase activity and determine tumor necrosis factor α and interleukin 6 concentrations. Hematoxylin-eosin staining of lungs at 24-h time point was performed to investigate the grade of acute lung injury.
resultsRats treated with VPA (300 mg/kg) showed significantly higher survival rates (85.7%) compared with the control (14.3%). Moreover, VPA significantly suppressed myeloperoxidase activity (marker of neutrophil-mediated oxidative damage) and inhibited levels of proinflammatory cytokine tumor necrosis factor α and interleukin 6 in the serum and peritoneal cavity. Meanwhile, the severity of acute lung injury was significantly reduced in VPA-treated animals.
conclusionsWe have demonstrated that VPA treatment improves survival and attenuates inflammation in a rodent two-hit model.
Indexed as
Identifiers
What OpenQuestion holds
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.