Human heart development slower than other mammals

The walls of the human heart are a disorganised jumble of tissue until relatively late in pregnancy, despite having the shape of a fully functioning heart, according to a pioneering study.

Experts from the University of Sheffield's Medical School collaborated on research to create the first comprehensive model of human heart development using observations of living foetal hearts. The results showed surprising differences from existing animal models.

Although scientists 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 research team, led by scientists at the University of Leeds 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 foetuses’ hearts.

Video courtesy of the University of Leeds

Martyn Paley, Professor of BioMedical Imaging at the University of Sheffield's Department of Cardiovascular Science, said: "We used our extensive expertise in Magnetic Resonance Imaging (MRI) physics and engineering to optimise the acquisition of very high spatial resolution isotropic 3D images of the foetal heart at later gestational ages using rapid FLASH sequences.

"This allowed the morphology of the foetal heart to be studied with unprecedented detail in collaboration with the University of Leeds and the other centres."

Early results are already suggesting 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’s development, a paper published in the Journal of the Royal Society Interface Focus reports that the there is little organisation of the human heart’s cells until 20 weeks into pregnancy.

A pig’s 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, added: “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.”

The research was conducted by a team including academics from the University of Sheffield, University of Leeds, the University of Edinburgh, the University of Nottingham, and the University of Manchester.

Additional information The full paper, “Antenatal architecture and activity of the human heart,” is published in the Journal of the Royal Society Interface Focus and has been published online at http://dx.doi.org/10.1098/rsfs.2012.0065 (DOI: 10.1098/rsfs.2012.0065). The University of Sheffield With nearly 25,000 of the brightest students from 125 countries coming to learn alongside 1,181 of the world’s best academics, it is clear why the University of Sheffield is one of the UK’s leading universities. Staff and students at Sheffield are committed to helping discover and understand the causes of things - and propose solutions that have the power to transform the world we live in. A member of the Russell Group, the University of Sheffield has a reputation for world-class teaching and research excellence across a wide range of disciplines. The University of Sheffield has been named University of the Year in the Times Higher Education Awards 2011 for its exceptional performance in research, teaching, access and business performance. In addition, the University has won four Queen’s Anniversary Prizes (1998, 2000, 2002, 2007), recognising the outstanding contribution by universities and colleges to the United Kingdom’s intellectual, economic, cultural and social life. One of the markers of a leading university is the quality of its alumni and Sheffield boasts five Nobel Prize winners among former staff and students. Its alumni have gone on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields. Research partners and clients include Boeing, Rolls-Royce, Unilever, Boots, AstraZeneca, GSK, ICI, Slazenger, and many more household names, as well as UK and overseas government agencies and charitable foundations. The University has well-established partnerships with a number of universities and major corporations, both in the UK and abroad. Its partnership with Leeds and York Universities in the White Rose Consortium has a combined research power greater than that of either Oxford or Cambridge.