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.
Graham Askew, Simon Walker, BBSRC (Jan 2018), £699,781
Jennifer Tomlinson, Royal Society (Jan 2018), £512,801
Jennifer Tomlinson, Royal Society-Research Fellows Enhancement Award (Dec 2017), £94,681
Helen Miller, AB AGri Grant (Dec 2017), £73,600
Simon Walker, Royal Society Enhancement Award (Dec 2017), £10,000
Carrie Ferguson, Bryan Taylor, Harry Rossiter, The Physiological Society (Dec 2017), £7,392
Ralf Richter, Royal Society (Dec 2017), £6,000
Christine Foyer, British Council Newton Fund (Dec 2017), £49,840
Adrian Whitehouse and colleagues in School of Chemistry and University of Liverpool, MRC (Nov 2017), £622,319
Michelle Peckham, Neil Ransom, MRC (Nov 2017), £495,159
Dave Lewis, British Council India (Nov 2017), £22,540
Elton Zeqiraj, Royal Society (Nov 2017), £15,000
Hannah Dugdale, Royal Society (Nov 2017), £15,000
Shaunna Burke, Cancer Research UK Innovation Grant (Nov 2017), £20,000
Alex O'Neill and colleagues in Chemistry, BBSRC (Nov 2017), £431,865
Jessica Kwok, Wings for Life (Nov 2017), £87,365
Tom Bennett, BBSRC (Oct 2017), £523,679
Neil Ranson, Darren Tomlinson, BBSRC (Oct 2017), £494,318
Nikita Gamper, BBSRC (Oct 2017), £490,426
Amanda Bretman and colleagues from UEA, NERC (Oct 2017), £430,886
Juan Fontana, Rosetrees Trust consumables grant (Oct 2017), £22,500
Helen Miller, DSM Nutritional Products AG (Sep 2017), £69,988
Neil Ranson, Juan Fontana, Mark Harris, Michelle Peckham, Ralf Richter, Peter Stockley, Patricija Van Oosten-Hawle and colleagues in Engineering, FMH and MAPS, Wellcome Trust Equipment Call (Sep 2017), £418,000
Jamie Johnston, Physiological Society (Sep 2017), £10,000
Frank Sobott, Adrian Goldman, Mark Harris, Andrew Macdonald, Stephen Muench, Sheena Radford and colleagues in FMH and MAPS, Wellcome Trust Equipment Call (Aug 2017), £415,000
Ralf Richter, David Brockwell, Eric Hewitt, Jessica Kwok, Emanuele Paci and MAPS/FMH, BBSRC (Jun 2017), £600,000
Eric Blair, Adrian Whitehouse, Nicola Stonehouse, Alison Baker, Richard Bayliss, Joan Boyes, Ryan Seipke, Sally Boxall and MAPS/FMH, BBSRC (Jun 2017), £376,000
Stefan Kepinski, Yoselin Benitez-Alfonso, Tom Bennett, Michelle Peckham, BBSRC (Jun 2017), £331,000
Roman Tuma, Lars Jeuken, Paul Millner, Sheena Radford, Peter Stockley and MAPS/FMH, BBSRC (Jun 2017), £222,000
Vas Ponnambalam, Darren Tomlinson, Stephen Wheatcroft, BHF (May 2017), £107,878
Graham Askew in collaboration with Bangor University, BBSRC (Mar 2017), £477,383
Stephen Muench, BBSRC (Mar 2017), £132,945
Nic Stonehouse, MRC (Mar 2017), £906,341
Bill Kunin, Steve Sait, BBSRC (Mar 2017), £602,831
Adrian Goldman, EU (Mar 2017), £546,576
Sheena Radford, Wellcome Trust (Mar 2017), £1,836,482
Beatrice Filippi, Royal Society (Mar 2017), £15,000
Tom Bennett, Royal Society (Mar 2017), £15,000
Jamie Johnston, Royal Society (Mar 2017), £15,000
Ryan Seipke, BBSRC (Feb 2017), £52,116
Mary O'Connell, BBSRC (Feb 2017), £46,986
Hannah Dugdale, NERC (Feb 2017), £504,138
Anastasia Zhuravleva, EPSRC (Jan 2017), £100,792