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.
Andrew Macdonald, Yorkshire Kidney Research Fund (Jul 2016), £108,285
Amanda Bretman, Leverhulme Trust
(Jul 2016), £107,128
Zarah Timsah, Wellcome Trust
(Jul 2016), £100,000
Adrian Whitehouse, Worldwide Cancer Research (Jul 2016), £107,570
Roman Tuma, BBSRC (Jul 2016), £107,433
Helen Miller, Innovate UK (Jun 2016), £109,647
Adrian Goldman, Royal Society
(Jun 2016), £250,000
James Deuchars, Dunhill Medical Trust (Jun 2016), £107,247
Keith Hamer, DEFRA Dept for Env. Food & Rural Affairs
(Jun 2016), £103,887
Richard Bayliss, EU - European Union
(Jun 2016), £108,176
Jamel Mankouri, British Lung Foundation
(Jun 2016), £105,557
Jamel Mankouri, John Barr, British Lung Foundation
(Jun 2016), £24,000
Zahra Timsah, Wellcome Trust (Jun 2016), £108,605
Andrew Macdonald, Kidney Research Fund UK
(Jun 2016), £108,110
Andrew MacDonald, Richard Foster, Stephen Griffin, Kidney Research Fund UK
(Jun 2016), £63,653
Edwin Chen, Academy of Medical Sciences (Jun 2016), £108,131
Edwin Chen, Academy of Medical Sciences
(Jun 2016), £98,110
Adrian Goldman, Royal Society (May 2016), £106,738
Peter Stockley, Wellcome Trust (May 2016), £1,246,487
John Ladbury, Christopher Jones, Cancer Research UK
(May 2016), £6,905
Elton Zaqiraj, Wellcome Trust (May 2016), £1,093,823
Adrian Whitehouse, Julie Aspden, BBSRC (May 2016), £457,270
Alison Baker, Miller Camargo-Valero, BBSRC
(May 2016), £451,124
Peter Urwin, BBSRC (May 2016), £432,379
John Trinick, R Elwyn Issac, Leverhulme Trust
(May 2016), £171,742
, British Council, UK
(May 2016), £17,793
Mark Harris, Horserace Betting Levy Board
(Apr 2016), £10,000
Peter Stockley, Neil Ranson, Roman Tuma, David Rowlands, MRC (Apr 2016), £341,225
Jamel Mankouri, Royal Society (Apr 2016), £332,396
Andrew Tuplin, MRC (Apr 2016), £508,170
Keith Hamer, DEFRA Darwin Initiative (Apr 2016), £327,744
Simon Goodman, British Council, UK
(Mar 2016), £35,800
, British Council, UK
(Mar 2016), £12,802
Katie Field, NERC
(Mar 2016), £186,411
Isuru Jayasinghe, Royal Society
(Mar 2016), £14,919
William Hoppitt, EU (Feb 2016), £34,345
Helen Miller, ABNA Ltd (Feb 2016), £115,000
Sarah Calaghan, Isuru Jayasinghe, BHF (Jan 2016), £52,050
Edwin Chen, Wellcome Trust (Jan 2016), £98,341
Patricija Van Oosten-Hawle, Wellcome Trust (Jan 2016), £89,900
James Duce, Alzheimer's Society (Jan 2016), £84,834
Andrew Smith, Rosetrees Trust (Jan 2016), £20,000
Richard Bayliss, Cancer Research UK (Jan 2016), £10,000
Richard Bayliss, BBSRC (Jan 2016), £8,000
Richard Bayliss, MRC (Jan 2016), £8,000
Thomas Edwards and colleagues in the School of Chemistry, EPSRC (Jan 2016), £2,228,732
David Brockwell, Sheena Radford, BBSRC (Dec 2015), £358,570
Stephanie Wright, Kay Kendall Leukaemia Fund (Dec 2015), £207,286
Stefan Kepinski, Michelle Peckham, BBSRC (Nov 2015), £461,760
Ryan Seipke, BBSRC (Nov 2015), £340,536
Paul Knox, BBSRC (Nov 2015), £40,000
Helen Miller, Agriculture & Horticulture Develpmnt Brd (Oct 2015), £63,560
Jessica Kwok, Wings For Life Spinal Cord Research (Oct 2015), £134,981
Joe Cockburn, Royal Society (Oct 2015), £14,960
Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2015), £340,937
Alan Berry, Wellcome Trust (Oct 2015), £752,365
Mark Harris, Thomas Edwards, John Barr and colleagues from the School of Chemistry, Wellcome Trust (Sep 2015), £204,959
Mark Harris, Royal Society (Sep 2015), £74,000
Zahra Timsah, Royal Society (Sep 2015), £15,000
Katie Field, Royal Society (Sep 2015), £14,700
Christine Foyer, Royal Society (Sep 2015), £12,000
Julie Aspden, MRC (Sep 2015), £633,020
Ian Hope, Marie-Anne Shaw, BBSRC (Aug 2015), £381,998
Helen Miller, ABNA Ltd (Aug 2015), £22,968
Alan Berry, Alex Breeze, Adam Nelson, BBSRC (Aug 2015), £479,490
Katie Field, BBSRC (Aug 2015), £830,381
Tim Benton, M & W MACK LTD (Aug 2015), £48,711
Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Jul 2015), £1,000,000