Evidence map›Paper›PMID 40036828›Full record

ArticleCardiovascular research2025

Evidence for intermittent coupling of intramyocardial small, engineered heart tissues acutely implanted into rabbit myocardium.

Eline Huethorst, Martin J Bishop, Francis L Burton, Chris Denning, Nikolaj Gadegaard, Rachel C Myles, Godfrey L Smith

Abstract read
In one paragraph

Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Eline HuethorstSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow G12 8TD, UK.ORCID 0000-0003-1900-4039
Martin J BishopResearch Department for Digital Twins in Healthcare, School of Biomedical Engineering and Imaging Sciences, King's College London, London SE1 7AR, UK.ORCID 0000-0002-6237-1902
Francis L BurtonSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow G12 8TD, UK.ORCID 0000-0002-6970-6250
Chris DenningBiodiscovery Institute, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham NG7 2RD, UK.ORCID 0000-0003-0802-8617
Nikolaj GadegaardSchool of Engineering, University of Glasgow, Glasgow G12 8LT, UK.ORCID 0000-0002-3396-846X
Rachel C MylesSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow G12 8TD, UK.ORCID 0000-0003-4670-361X
Godfrey L SmithSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow G12 8TD, UK.ORCID 0000-0003-4821-9741

Funding

British Heart Foundation FS/16/55/32731British Heart Foundation Centre for Regenerative Medicine CRMR/21/290009British Heart Foundation Centre of Research Excellence RE/18/63/42/17British Heart Foundation Project PG/22/10871British Heart Foundation Project PG/22/11159
6 · The paper itself

Abstract

aimsElectrical integration of human-induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM)-based tissue with the host myocardium is a requirement of successful regeneration therapy. This study was designed to identify electrical coupling in the acute phase (1-2 h) post-grafting using an ex vivo model. METHODS AND

resultsSmall, engineered heart tissues (mini-EHTs), consisting of ∼50 000 hiPSC-CMs on a hydrogel (spontaneous rate 0.34 ± 0.05 Hz), were loaded with Cal520-AM. EHTs were implanted sub-epicardially into a Langendorff-perfused rabbit heart after blebbistatin treatment. For up to 100 min, a continuous pseudo-electrocardiogram was recorded during sinus rhythm (rate 2.0-3.5 Hz). At 25 min intervals, EHT calcium transients (CaTs) were recorded for 10-20 s (no contraction group). To study the influence of mechanical activity, blebbistatin was washed off after implantation (contraction recovery group). Periodic entrainment of EHTs with the myocardium was detected less often (P = 0.011) in the no contraction group (1/9 hearts) than in the contraction recovery group (5/6 hearts). The average coupling delay (QRS-CaT) and the difference in consecutive delays (Δdelay) were 89 ± 50 and 10 ± 3 ms, respectively (n = 12 traces; N = 6 hearts). Coupling ratios (QRS:CaT) varied from 2:1 to 4:1. These coupling parameters were not significantly different in the two experimental groups. Modelling of hiPSC-CM tissue separated by a 25 μm saline gap from the myocardium demonstrated field-effect coupling with similarly variable activation delays. Importantly, coupling failed with a gap of 100 μm.

conclusionEHT entrainment is possible immediately after grafting and has features compatible with field-effect coupling. Sensitivity to the gap dimensions may explain why entrainment is more common in actively contracting myocardium.

Indexed as

Excitation Contraction CouplingInduced Pluripotent Stem CellsMyocardial ContractionMyocardiumMyocytes, CardiacTissue EngineeringAction PotentialsAnimalsCalcium SignalingCells, CulturedHeart RateHumansHydrogelsIsolated Heart PreparationRabbitsRegenerationHydrogelsElectric field effectGraft-host couplingHiPSC-CM implantationIntramyocardial implantationRabbit heart

Identifiers

PMID40036828
PMCPMC12477673

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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.