Evidence map›Paper›PMID 41812219›Full record

ArticleESC heart failure2026

Optimized murine HFpEF models for translational preclinical studies.

Bailey McIntosh, Ali Ali Mohamed Elbassioni, Anmar Raheem, Eilidh A MacDonald, Stuart A Nicklin, Yen Chin Koay, Ewan R Cameron, Christopher M Loughrey, John F O'Sullivan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESC heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
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

9 authors.

Bailey McIntoshSchool of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales 2050, Australia.ORCID 0009-0003-9948-0242
Ali Ali Mohamed ElbassioniSchool of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Anmar RaheemSchool of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Eilidh A MacDonaldSchool of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.ORCID 0000-0002-7771-754X
Stuart A NicklinSchool of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
Yen Chin KoayCardiometabolic Medicine, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales 2050, Australia.
Ewan R CameronSchool of Biodiversity One Health and Veterinary Medicine, College of Medical Veterinary & Life Sciences, University of Glasgow, 464 Bearsden Road, Glasgow G61 1QH, UK.
Christopher M LoughreySchool of Cardiovascular and Metabolic Health, Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, UK.
John F O'SullivanCardiometabolic Medicine, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales 2050, Australia.

Funding

British Heart Foundation RG/20/6/35095British Heart Foundation Centre of Excellence RE/18/6/34217Clinician-Scientist DOH1003Clinician-Scientist DOH1006Jennie Mackenzie bequestNational Heart Foundation Future Leader Fellowship NHF107180National Heart Foundation Level 3 Future Leader Fellowship NHF109373Newton-Mosharafa FundNHF Vanguard NHF110518NHMRC-MRFF Cardiovascular Health Mission 107180NSW Cardiovascular Collaborative OHMR23-251985NSW Health Early-Mid Career Fellowship
6 · The paper itself

Abstract

introductionThe most clinically representative murine models of heart failure with preserved ejection fraction (HFpEF) include a '2-hit' model combining nitrosative stress with metabolic perturbation and a '3-hit' model that also includes ageing. Both models have important limitations with regard to substrain and sex.

methodsThe 2-hit model protocol was modified to reproduce HFpEF in both C57BL/6N and 6J mice by increasing L-NAME doses (0.5 g/L to 1.75 g/L) and protocol lengths (7 weeks to 13 weeks). For the 3-hit model, in addition to deoxycorticosterone pivalate (DOCP), we added 1% NaCl drinking water to enhance and prolong the effect of DOCP ('4-hit'). To maintain the phenotype, a second bolus of DOCP was administered after 8 weeks.

resultsHFpEF was successfully induced in C57BL/6J mice when exposed to a 13-week 2-hit L-NAME protocol with gradually increasing dosage from 1.0 to 1.75 g/L. For the 4-hit mice, a clear HFpEF phenotype was observed in C57BL/6N and 6J mice in both male and females, and maintained for up to 12 weeks.

conclusionThese modifications ensure the 2-hit model is induced in J substrain of C57BL/6 mice. The 4-hit model prevents aldosterone escape and enhances reproducibility across sexes and substrains.

Indexed as

Heart FailureStroke VolumeTranslational Research, BiomedicalAnimalsDisease Models, AnimalFemaleMaleMiceMice, Inbred C57BLNG-Nitroarginine Methyl EsterNG-Nitroarginine Methyl EsterHeart failureHFpEFHypertensionObesityPreclinical model

Identifiers

PMID41812219
PMCPMC13036831

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LicenceCC BY
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Registered trials

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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.