Evidence map›Paper›PMID 28579457›Full record

ArticleBiochimica et biophysica acta. Molecular basis of disease2017

Metformin ameliorates gender-and age-dependent hemodynamic instability and myocardial injury in murine hemorrhagic shock.

Dzmitry Matsiukevich, Giovanna Piraino, Patrick Lahni, Paul W Hake, Vivian Wolfe, Michael O'Connor, Jeanne James, Basilia Zingarelli

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

Article in Biochimica et biophysica acta. Molecular basis of disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 3 pooled it
1.0field-weighted citation impact, top 25% 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

21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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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 1 institution in 1 country.

Dzmitry MatsiukevichDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Giovanna PirainoDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Patrick LahniDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Paul W HakeDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Vivian WolfeDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Michael O'ConnorDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Jeanne JamesDepartment of Pediatrics, Cardiovascular Imaging Core of the Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Basilia ZingarelliDepartment of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: basilia.zingarelli@cchmc.org.
Cincinnati Children's Hospital Medical Center · US

Funding

PPARgamma and PPARgamma agonists in septic shockR01GM067202 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI ZINGARELLI, BASILIA · 2003 to 2015
$3.9M
AGE-DEPENDENT MECHANISMS OF METABOLIC RECOVERY IN HEMORRHAGIC SHOCKR01GM115973 · NIGMS · CINCINNATI CHILDRENS HOSP MED CTR · PI ZINGARELLI, BASILIA · 2015 to 2022
$2.7M
NIGMS NIH HHS R01 GM067202NIGMS NIH HHS R01 GM115973
6 · The paper itself

Abstract

Severity of multiple organ failure is significantly impacted by age and gender in patients with hemorrhagic shock. However, the molecular mechanisms underlying the enhanced organ injury are not fully understood. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of metabolic responses during stress. We investigated whether hemorrhage-induced myocardial injury is age and gender dependent and whether treatment with metformin, an AMPK activator, affords cardioprotective effects. C57/BL6 young (3-5months) and mature (9-12months) male and female mice were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with blood and Lactated Ringer's solution. Vehicle-treated young and mature mice of both genders had a similar elevation of plasma inflammatory cytokines at 3h after resuscitation. However, vehicle-treated male mature mice experienced hemodynamic instability and higher myocardial damage than young male mice, as evaluated by echocardiography, histology and cardiovascular injury biomarkers. There was also a gender-dependent difference in cardiovascular injury in the mature group as vehicle-treated male mice exhibited more severe organ injury than female mice. At molecular analysis, vehicle-treated mature mice of both genders exhibited a marked downregulation of AMPKα activation and nuclear translocation of peroxisome proliferator-activated receptor γ co-activator α when compared with young mice. Treatment with metformin improved cardiovascular function and survival in mature animals of both genders. However, specific cardioprotective effects of metformin were gender-dependent. Metformin did not affect hemodynamic or inflammatory responses in young animals. Thus, our data suggest that targeting metabolic recovery with metformin may be a potential treatment approach in severe hemorrhage in adult population.

Indexed as

Sex CharacteristicsAgingAMP-Activated Protein KinasesAnimalsBiomarkersCardiotonic AgentsEnzyme ActivatorsFemaleHeart InjuriesHemodynamicsMaleMetforminMiceMyocardiumPPAR gammaShock, HemorrhagicAMP-Activated Protein KinasesBiomarkersCardiotonic AgentsEnzyme ActivatorsMetforminPPAR gammaAgeAMP-activated protein kinase (AMPK)GenderHemorrhagic shockMetforminPeroxisome proliferator-activated receptor-γ co-activator α (PGC-1α)

Identifiers

PMID28579457
PMCPMC5653443
OpenAlexW2621191844

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.