Evidence map›Paper›PMID 24957668›Full record

ArticleSurgery2014

Histone deacetylase inhibitor treatment attenuates coagulation imbalance in a lethal murine model of sepsis.

Ting Zhao, Yongqing Li, Baoling Liu, Erxi Wu, Martin Sillesen, George C Velmahos, Ihab Halaweish, Hasan B Alam

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Surgery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Ting ZhaoDepartment of Surgery, Division of Trauma, Emergency Surgery & Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Yongqing LiDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Baoling LiuDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Erxi WuDepartment of Pharmaceutical Sciences, North Dakota State University, Fargo, ND.
Martin SillesenDepartment of Surgery, Division of Trauma, Emergency Surgery & Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, MA; Department of Anesthesia, Center of Head and Orthopedics, Copenhagen University Hospital, Copenhagen, Denmark.
George C VelmahosDepartment of Surgery, Division of Trauma, Emergency Surgery & Surgical Critical Care, Massachusetts General Hospital/Harvard Medical School, Boston, MA.
Ihab HalaweishDepartment of Surgery, University of Michigan, Ann Arbor, MI.
Hasan B AlamDepartment of Surgery, University of Michigan, Ann Arbor, MI. Electronic address: alamh@med.umich.edu.
University of Michigan–Ann Arbor · USHarvard University · USCopenhagen University Hospital · DKNorth Dakota State University · US

Funding

Modulation of Acetylation in the Treatment of Lethal InjuriesR01GM084127 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALAM, HASAN B · 2009 to 2019
$2.6M
NIGMS NIH HHS R01 GM084127NIGMS NIH HHS R01GM084127
6 · The paper itself

Abstract

backgroundSepsis has a profound impact on the inflammatory and hemostatic systems. In addition to systemic inflammation, it can produce disseminated intravascular coagulation, microvascular thrombosis, consumptive coagulopathy, and multiple organ failure. We have shown that treatment with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDACI), improves survival in a lethal model of cecal ligation and puncture (CLP) in mice, but its effect on coagulation remains unknown. The goal of this study was to quantify the impact of SAHA treatment on coagulopathy in sepsis.

methodsC57BL/6J mice were subjected to CLP, and 1 hour later given intraperitoneally either SAHA dissolved in dimethyl sulfoxide (DMSO) or DMSO only. Sham-operated animals were handled in similar manner without CLP. Blood samples were collected by cardiac puncture and evaluated using the TEG 5000 Thrombelastograph Hemostasis Analyzer System.

resultsCompared with the sham group, all animals in DMSO vehicle group died within 72 hours, and developed coagulopathy that manifested as prolonged initial fibrin formation and fibrin cross-linkage time, and decreased clot formation speed, platelet function, and clot rigidity. SAHA treatment significantly improved survival and was associated with improvement in fibrin cross-linkage and clot formation, as well as platelet function and clot rigidity, without a significant impact on the clot initiation parameters.

conclusionSAHA treatment enhances survival and attenuates sepsis-associated coagulopathy by improving fibrin cross-linkage, rate of clot formation, platelet function, and clot strength. HDACI may represent a novel therapeutic strategy for correcting sepsis-associated coagulopathy.

Indexed as

AnimalsBlood CoagulationBlood Coagulation DisordersBlood PlateletsDisease Models, AnimalDisseminated Intravascular CoagulationFibrinHistone Deacetylase InhibitorsHydroxamic AcidsMaleMiceMice, Inbred C57BLSepsisThrombelastographyVorinostatFibrinHistone Deacetylase InhibitorsHydroxamic AcidsVorinostat

Identifiers

PMID24957668
PMCPMC4267526
OpenAlexW2014079319

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.