A faculty-led team developing the first comprehensive model of human heart development using observations of living foetal hearts found surprising differences from existing animal models.
Although they saw four clearly defined chambers in the foetal heart from the eighth week of pregnancy, they did not find organised muscle tissue until the 20th week, much later than expected.
Developing an accurate, computerised simulation of the foetal heart is critical to understanding normal heart development in the womb and, eventually, to opening new ways of detecting and dealing with some functional abnormalities early in pregnancy.
Studies of early heart development have previously been largely based on other mammals such as mice or pigs, adult hearts and dead human samples. The Leeds-led team is using scans of healthy foetuses in the womb, including one mother who volunteered to have detailed weekly ECG (electrocardiography) scans from 18 weeks until just before delivery.
This functional data is incorporated into a 3D computerised model built up using information about the structure, shape and size of the different components of the heart from two types of MRI (Magnetic Resonance Imaging) scans of dead foetuses hearts.
Early results from the project, which involves researchers from Leeds, the University of Edinburgh, the University of Nottingham, the University of Manchester and the University of Sheffield, show that the human heart may develop on a different timeline from other mammals.
While the tissue in the walls of a pig heart develops a highly organised structure at a relatively early stage of a foetus development, a paper from the Leeds-led team published in the Journal of the Royal Society Interface Focus reports that the there is little organisation of the human hearts cells until 20 weeks into pregnancy.
A pigs pregnancy lasts about three months and the organised structure of the walls of the heart emerge in the first month of pregnancy. The new study only detected similar organised structures well into the second trimester of the human pregnancy. Human foetuses have a regular heartbeat from about 22 days.
Dr Eleftheria Pervolaraki, Visiting Research Fellow at the University of Leeds School of Biomedical Sciences, said: For a heart to be beating effectively, we thought you needed a smoothly changing orientation of the muscle cells through the walls of the heart chambers. Such an organisation is seen in the hearts of all healthy adult mammals.
Foetal hearts in other mammals such as pigs, which we have been using as models, show such an organisation even early in gestation, with a smooth change in cell orientation going through the heart wall. But what we actually found is that such organisation was not detectable in the human foetus before 20 weeks, she said.
Professor Arun Holden, also from Leeds School of Biomedical Sciences, said: The development of the foetal human heart is on a totally different timeline, a slower timeline, from the model that was being used before. This upsets our assumptions and raises new questions. Since the wall of the heart is structurally disorganised, we might expect to find arrhythmias, which are a bad sign in an adult. It may well be that in the early stages of development of the heart arrhythmias are not necessarily pathological and that there is no need to panic if we find them. Alternatively, we could find that the disorganisation in the tissue does not actually lead to arrhythmia.
A detailed computer model of the activity and architecture of the developing heart will help make sense of the limited information doctors can obtain about the foetus using non-invasive monitoring of a pregnant woman.
Professor Holden said: It is different from dealing with an adult, where you can look at the geometry of an individuals heart using MRI (Magnetic Resonance Imaging) or CT (Computerised Tomography) scans. You cant squirt x-rays at a foetus and we also currently tend to avoid MRI, so we need a model into which we can put the information we do have access to.
He added: Effectively, at the moment, foetal ECGs are not really used. The textbooks descriptions of the development of the human heart are still founded on animal models and 19th century collections of abnormalities in museums. If you are trying to detect abnormal activity in foetal hearts, you are only talking about third trimester and postnatal care of premature babies. By looking at how the human heart actually develops in real life and creating a quantitative, descriptive model of its architecture and activity from the start of a pregnancy to birth, you are expanding electrocardiology into the foetus.
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000
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Alan Berry, Wellcome Trust (Oct 2015), £752,365
Julie Aspden, MRC (Oct 2015), £633,020
Steve Sait, NERC (Oct 2015), £386,061
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Eileen Ingham, John Fisher, EPSRC (Jul 2015), £1,458,439
Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019
Alex O'Neill, MRC (Jul 2015), £249,822
Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034
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Helen Miller, ABNA Ltd (Jul 2015), £22,968
Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475
Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693
Elwyn Isaac, EU (Jun 2015), £238,915
Christine Foyer, BBSRC (Jun 2015), £160,401
Adrian Goldman, EU (Jun 2015), £116,331
David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378
Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672
Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987
Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184
Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021
Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703
Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726
Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103
Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407
Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900
Andrew Tuplin, Royal Society (Mar 2015), £15,000
Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770
Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960
Stuart Egginton, BHF (Mar 2015), £272,979
Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066
Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171
Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000
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Paul Knox, BBSRC (Jan 2015), £5,000
Andrew Peel, BBSRC (Jan 2015), £359,077
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Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521
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Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015
Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937
Bill Kunin, EU (Jan 2015), £157,490
John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000
Chris Hassall, Royal Society (Dec 2014), £14,500