Evidence map›Paper›PMID 24205315›Full record

ArticlePloS one2013

Direct, differential effects of tamoxifen, 4-hydroxytamoxifen, and raloxifene on cardiac myocyte contractility and calcium handling.

Michelle L Asp, Joshua J Martindale, Joseph M Metzger

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03112031 (A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.2field-weighted citation impact, top 20% 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.

NCT03112031 phase2completednot on this mapstarted 2017, after this paper: background citation

A Randomized Trial of Tamoxifen Combined With Amphotericin B and Fluconazole for Cryptococcal Meningitis

TypeinterventionalSponsorOxford University Clinical Research Unit, VietnamRan2017 to 2018Enrolled50ConditionsMeningitis Streptococcal, Hiv, Meningitis, MeningoencephalitisArmsTamoxifen, Amphotericin B, Fluconazole
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 31 citations in OpenAlex.

  1. Trial
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  6. Considering impact of age and sex on cardiac cytoskeletal components.American journal of physiology. Heart and circulatory physiology · 2024
    Review
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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

3 authors at 1 institution in 1 country.

Michelle L AspDepartment of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota, United States of America.
Joshua J Martindale
Joseph M Metzger
University of Minnesota Medical Center · US

Funding

Troponin and Heart Function in Heath and DiseaseR01HL059301 · NHLBI · UNIVERSITY OF MINNESOTA · PI METZGER, JOSEPH MARK · 1998 to 2014
$5.1M
Dystrophin Function in Aging HeartR01AG034107 · NIA · UNIVERSITY OF MINNESOTA · PI METZGER, JOSEPH MARK · 2010 to 2014
$1.7M
Novel calcium buffer for the treatment of diastolic heart failureF32HL115876 · NHLBI · UNIVERSITY OF MINNESOTA · PI LAW, MICHELLE LYNN · 2012 to 2014
$163k
NHLBI NIH HHS 1F32HL115876NHLBI NIH HHS F32 HL115876NHLBI NIH HHS R01 HL059301NIA NIH HHS R01 AG034107
6 · The paper itself

Abstract

Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT), and related drug raloxifene (Ral) on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca²⁺ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca²⁺ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca²⁺ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy.

Indexed as

AnimalsBiomechanical PhenomenaCalciumFemaleMiceMuscle ContractionMyocytes, CardiacRaloxifene HydrochlorideRatsRats, Sprague-DawleySarcomeresTamoxifenafimoxifeneCalciumRaloxifene HydrochlorideTamoxifen

Identifiers

PMID24205315
PMCPMC3811994
OpenAlexW2013766385

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.