Figure 3 supplementary video #1 (above). Click image to play video in a new window. This movie was made from the series of snapshots generated by an MRI. In this case, we are looking through a rabbit’s heart, side-on, starting with the side nearest the rib cage. Note the intricate structure of the heart walls, and of the papillary muscle (visible as dark strands in the open chambers of the heart). Papillary muscles contract with the walls, to hold closed the valves (“doors” between chambers of the heart) so the blood flows in the proper direction when the heart contracts. Research funded by a UK Biotechnology and Biological Sciences Research Council grant award to Dr.s Peter Kohl, Jurgen Schneider, and David Gavaghan.

Figure 3 supplementary video #2 (above). Click image to play video in a new window. Another MRI sequence, this time looking through a rabbit heart from top to bottom. The circle visible at the beginning of the movie is the aorta, the largest artery in the body. The thin wavy lines that come in and out of the picture in open areas of the heart are the edges of the valves. The strands of the papillary muscles are visible later in the video. For a "tour" of a dataset very similar to this one, see http://news.bbc.co.uk/1/hi/health/7774016.stm. Research funded by a UK Biotechnology and Biological Sciences Research Council grant award to Drs. Peter Kohl, Jurgen Schneider, and David Gavaghan.

Figure 5 supplementary video (above). Click image to play video in a new window. Video demonstrating the normal electrical activity in the heart, visualised by voltage optical mapping. You can see the signal starting at the bottom (apex) of the heart, and traveling upwards. This rabbit heart has been chemically paralyzed, so the video is of electrical activity only. If the heart were allowed to move, the electrical signal would be followed closely by near-simultaneous muscle contraction following the same wave pattern. Research funded by a UK Engineering and Physiological Sciences Research Council Fellowship award to Dr. T. Alexander Quinn.

Figure 6 supplementary video (above). Click image to play video in a new window. Video of a heartbeat on a computerized “mesh” generated for the preDiCT project. This mesh is based on a rabbit heart, and combines information from many sources to accurately represent:

• Behavior of individual cells and the transmission of electrical signal between cells
• Heart wall thickness and internal structure
• Orientation of muscle fibers within the tissue (the electrical signal goes in all directions, but is transmitted much more quickly “along the grain” of the muscle)
• The special conduction system in the heart: a sort of telegraph-wire system for quickly taking the electrical signal from the pacemaker at the top of the heart, to the lower part of the heart where the contractions must begin.

Figure 7 supplementary video (above). Click image to play video in a new window. A tour of a tiny part of a single cardiac muscle cell (using electron microscope tomography). Important cellular structures can be tracked through each frame, and then be reconstructed in 3D. You can see parts of four mitochondria (the cell’s power station, looking like zebra-striped patches in the movie); their relation to a calcium storage compartments (curved membrane structures); parts of the cell surface membrane that dive into the middle of the cell (yellow) and microtubules (two initially circular un-filled areas in the centre between mitochondria), and the myo-filaments (the horizontal mid-layer) that allow the muscle cell to generate force. The 3D pixels (voxels) underlying this image are only a few nanometers (millionths of a meter) in size. Image courtesy of of Ms. Fleur Mason and Drs. Patrizia Camelliti, Mary Morphew, and Andreas Hoenger, University of Oxford and University of Colorado, Boulder.

About the authors

Katherine Fletcher
Project Manager, Virtual Physiological Human Network of Excellence
University of Oxford
Fletcher is a project manager working for the University of Oxford. She is currently helping coordinate the EC-funded Virtual Physiological Human Network of Excellence and the JISC-funded DataFlow project (building open-source tools to help researchers keep and share their data). She also coordinated the EC-funded preDiCT project (2008-2011), which developed state-of-the-art cardiac electrophysiology models. She grew up in Gretna, Nebraska, graduated from William Jewell College (Liberty, MO) with a BA in International Relations, and the University of Sussex (Brighton, UK) with an MA in Global Political Economy, and now lives in Oxford.

Dr. Peter Kohl
Chair, Cardiac Biophysics and Systems Biology
National Heart and Lung Institute, Imperial College London
Kohl studied Medicine and Biophysics at the Moscow Pirogov Institute (1981-1987) and, after post-graduate training and research at the Berlin Charité (PhD 1990, Facharzt 1991), he joined the Cardiac Electrophysiology Chair group of Professor Denis Noble at Oxford (1992). In 1998, Peter set up at Oxford the Cardiac Mechano-Electric Feedback Lab, initially as a Royal Society Research Fellow, and subsequently as a Senior Fellow of the British Heart Foundation. While at Oxford, he held a Research Fellowship at Keble College (2002-2004) and was the Tutorial Fellow in Biomedical Sciences at Balliol (2004-2010). Since 2010, he is also an Affiliated Senior Fellow of the Oxford Department of Computer Science. In October 2010, Peter has taken up the Chair in Cardiac Biophysics and Systems Biology at the National Heart and Lung Institute, Imperial College London.

Dr. Denis Noble
Emeritus Professor of Cardiovascular Physiology
University of Oxford
Noble , CBE, FRS, is Emeritus Professor of Cardiovascular Physiology at the University of Oxford. He was Chairman of the International Union of Physiological Sciences (IUPS) World Congress in 1993, Secretary-General of IUPS from 1993-2001 and is now President of IUPS. His previous publications include the seminal set of essays, The Logic of Life (Boyd and Noble, Oxford University Press, 1993), and he played a major role in launching the Physiome Project, one of the international components of the systems biology approach. Science magazine included him amongst its review authors for its issue devoted to the subject in 2002.