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.
Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521
Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015
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
Ryan Seipke, Royal Society (Nov 2014), £13,700
Alan Berry, Wellcome Trust (Oct 2014), £749,865
Ian Hope, Marie-Anne Shaw, BBSRC (Oct 2014), £396,565
Alison Ashcroft, Peter Stckley, Sheena Radford, Nic Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2014), £340,937
Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302
Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475
Paul Knox, EU (Oct 2014), £167,229
Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453
Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480
Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878
Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437
Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424
Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759
Andrew Peel, BBSRC (Sep 2014), £371,598
Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684
Lars Jeuken, BBSRC (Sep 2014), £313,463
Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763
Neil Ranson, BBSRC (Aug 2014), £355,253
Stuart Egginton, BHF (Aug 2014), £271,094
Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665
Peter Henderson, Leverhulme Trust (Aug 2014), £15,222
Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880
Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787
Sheena Radford, Univesity of Michigan (Jul 2014), £138,452
Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960
John Trinick, BHF (Jun 2014), £222,614
Chris West, Leverhulme Trust (Jun 2014), £181,241
Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174
Christine Foyer, Royal Society (May 2014), £24,000
David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661
Peter Stockley, Wellcome Trust (Apr 2014), £251,019
Mike McPherson, Wellcome Trust (Apr 2014), £146,596
Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237
Elwyn Isaac, DEFRA (Apr 2014), £126,512
Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350
Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874
Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140
Tim Benton, Technology Strategy Board (Apr 2014), £24,969
Bill Kunin, Technology Strategy Board (Apr 2014), £21,244
Dave Westhead, MRC (Apr 2014), £18,304