The Spark of Life: Electricity in the Human Body

by Ashcroft, Frances

  A heart attack results from disruption of the blood supply to the heart and is commonly caused by blockage of one of the coronary arteries. As the tissues downstream of the blockage are deprived of oxygen they start to die. This may trigger ventricular fibrillation because the resulting tissue damage prevents the synchronized spread of electrical signals across the heart. Different groups of heart cells then go their own way and start to beat at different times. As in any society, cooperation between the component parts of the heart is vital for it to work effectively.

  Restoring the Rhythm

  If the heart beats irregularly, an artificial pacemaker is often used to correct its rhythm. Early pacemakers were large and bulky machines, about the size of a washing machine, and they were supplied with mains electricity. Consequently, the patient could not move around easily. They also had another disadvantage: they stopped when the electricity supply failed. In the 1950s, Dr C. Walton Lillehei was doing pioneering open-heart surgery on ‘blue babies’ at the University of Minnesota. These children were born with a hole between the left and right ventricles, which results in the blood bypassing the lungs, so that oxygen uptake is much reduced. After surgery to repair the hole, some babies suffered from short-term heart block; tissue damage meant that the electrical signals from their sinoatrial node did not reach the ventricles and their hearts failed to beat properly. In such cases, Lillehei used an artificial pacemaker machine until the child’s heart healed. This usually took one or two weeks.

  Unfortunately, a major power blackout in Minneapolis in October 1957 resulted in the death of one of the ‘blue babies’. Infuriated, Lillehei contacted Medtronic, the electronics company that made the machines, and asked for something that ran on batteries. He was in for a surprise, for in less than a month their engineer Earl Bakken returned with an artificial pacemaker that did indeed run on batteries – but it was now shrunk to the size of a sandwich. Transistorized circuits were the key to this miniaturization.

  Bakken wrote in his autobiography, One Man’s Full Life, ‘Back at the garage, I dug out a back issue of Popular Electronics magazine in which I recalled seeing a circuit for an electronic, transistorized metronome. The circuit transmitted clicks through a loudspeaker; the rate of the clicks could be adjusted to fit the music. I simply modified that circuit and placed it, without the loudspeaker, in a four-inch-square, inch-and-a-half-thick metal box with terminals and switches on the outside – and that, as they say, was that.’ He had intended his prototype as an experimental device for testing on animals and was stunned to discover, when he visited the hospital the next day, that it was already being used on patients. Lillehei calmly informed him that as the device worked he didn’t want to waste a minute before using it to help save patients’ lives. It was so successful that similar pacemakers were soon introduced throughout the world, and Medtronic became a major supplier.

  Just one year later, the first implantable pacemaker was used, in a forty-three-year-old Swedish patient called Arne Larsson. Arne suffered from complete heart block and his death seemed inevitable. His wife, however, had other ideas. She had heard of experiments being carried out on dogs at the Karolinska Hospital in Stockholm and decided that the technology might save her husband. Apparently she was extremely persuasive because she convinced the surgeon Åke Senning and the engineer Rune Elmqvist to help. Rune built the pacemaker in his kitchen. It failed within three hours of implantation, so Arne was given another one the next morning, which lasted just a few weeks. These failures did not put him off, however, and he eventually received twenty-six different pacemakers. The pacemaker enabled him to lead an essentially normal life – and he made good use of it, acting as a patient advisor and advocate for pacemakers throughout the world. He died forty-three years after receiving his first pacemaker, at the age of eighty-six, his bravery and willingness to act as a human guinea pig having doubled his lifespan.

  The concept of the artificial pacemaker is very simple. The pacemaker supplies a small electric current which substitutes for the heart’s own. This is achieved by inserting a wire into the right ventricle of the heart. It is usually threaded into place through one of the great veins, but in some cases the chest is opened and the wire placed directly on the heart’s surface. The lead is then connected to the pacemaker, which applies small electric shocks to drive the heart at the right rate. The pacemaker also contains a battery and, sometimes, electronic circuits that can sense the patient’s own heart rhythm and adjust it as needed. Once it is clear the device is working, it is implanted in the chest (usually in front of the shoulder), between the muscle and the subcutaneous fat. The first pacemaker Arne received was the size of a hockey puck, but today they can be as small as a ten-pence piece. They need replacing every five to ten years, depending on how long the battery lasts. As electromagnetic interference can cause pacemakers to malfunction, people with pacemakers must avoid high magnetic fields, cellphones and electronic equipment that generates stray electric fields.

  Packer Whackers

  Everyone is familiar with the typical emergency-room drama in which the patient is surrounded by a throng of medical staff, desperately working to save their life. Suddenly, the regular beep of the heart monitor ceases, the normal ECG vanishes to be replaced by a flat line, and someone screams ‘Arrest!’ Controlled panic ensues. Within seconds, large paddles are slapped onto the patient’s chest and with a warning cry of ‘Clear!’ an electric shock is administered. The patient’s chest jerks violently, the heart is restarted and the heart monitor springs into action once again.

  But this dramatic scene is far from accurate. There is usually no jerking of the patient in response to the electric shock – this is mere poetic licence. More significantly, in real life an electric shock is not used to restart a patient’s heart. Dramatic resuscitations are commonplace in modern medicine, but they do not occur in patients whose hearts have stopped, but rather in those whose hearts are fibrillating – whose ventricles are beating so asynchronously that the heart is reduced to a twitching lump of flesh that is quite unable to pump blood. And the electric current is not used to start the heart, but to stop it. As previously mentioned, the hope is that when the heart spontaneously restarts, the natural pacemaker cells in the sinus node will take over and the normal rhythm will be restored.

  It is possible the popular misconception has arisen from the use of the term ‘cardiac arrest’. This does not mean, as might be surmised, that the heart has stopped contracting and is totally still. Rather it refers to the fact that blood flow is arrested. Although individual heart cells continue to contract, they fail to do so in synchrony so that the heart is no longer an effective pump. Within a few minutes the brain dies because of lack of oxygen, and eventually the heart itself ceases to beat for the same reason. Unless the victim suffers a cardiac arrest in hospital, cardiopulmonary resuscitation is required to keep them alive until a defibrillator arrives. Artificial respiration is carried out and the heart is manually compressed by pumping the chest with the heels of the hands, forcing blood out of the heart and around the body. The right speed is vital – too fast and the heart has insufficient time to refill between compressions, too slow and the tissues suffer from lack of oxygen. A rate of 100 compressions per minute is just right. Serendipitously, the Bee Gees’ hit song ‘Staying Alive’ has almost exactly the right rhythm and has been used as a training aid for doctors. Although it also has a near-perfect beat, ‘Another One Bites the Dust’, by Queen, seems rather less appropriate.

  Defibrillators were not commonly carried in Australian ambulances before 1990. That all changed when Kerry Packer, a billionaire well known for his controversial and flamboyant character, had a cardiac arrest while playing polo. By chance, the ambulance that attended the scene was carrying a portable defibrillator. Despite being clinically dead for several minutes, Packer survived. He is alleged to have said of his near-death experience, ‘The good news is there is no devil. The bad news is there is no Heaven.’ After his recovery, he do
nated a large sum of money (2.5 million Australian dollars) to equip half the ambulances in the state of New South Wales with portable defibrillators, on the condition that the government paid for the other half. As a consequence, the machines are colloquially known in Australia as ‘Packer whackers’. Many Australians owe their lives to his philanthropy.

  In recent years, defibrillators have proliferated, and new versions are available that can be used by non-medical operators. In the UK, they are found at railway stations, on airplanes, and in other public places. Although the best-known defibrillators are external devices that are placed on the chest, much smaller implantable devices are also available for people who are at risk of fibrillation. These constantly monitor the heart’s rhythm and when necessary deliver an electric shock to reset it back to normal. People with implantable defibrillators can live a normal life secure in the knowledge that they have a built-in ‘life-saver’. These apparently deliver quite a shock – it is said to feel a bit like being thumped in the chest.

  To Hell and Back

  In November 2003, the rock singer Meat Loaf, best known for his performance in the Rocky Horror Show and his hit song ‘Bat out of Hell’, collapsed on stage during a concert at Wembley in front of a large audience. He was rushed to hospital, where he was found to have a rare heart ailment known as Wolff-Parkinson-White syndrome. He later said, ‘I remember not being able to sing the lyrics for the song “All Revved Up”, walking over to where the girls were and starting to fall.’ He thought he’d had a heart attack on stage.

  Wolff-Parkinson-White syndrome is a congenital condition that affects between 1 and 3 per cent of the population. It usually only causes problems when the heart rate is very fast, as occurs when someone is stressed or exercising heavily. The sudden unexpected death of very fit athletes due to cardiac arrest, such as that of the ice hockey player Bruce Melanson, is often due to Wolff-Parkinson-White syndrome. Other sufferers have been luckier. LaMarcus Aldridge, an American basketball player with the Portland Trailblazers retired from a game against the Los Angeles Clippers, complaining of dizziness, shortness of breath and an irregular heartbeat. He was subsequently found to have Wolff-Parkinson-White syndrome. Both he and Meat Loaf were successfully treated for the condition.

  In the normal heart, electrical signals generated in the atria pass to the ventricles via a specialized conduction pathway known as the atrio-ventricular (A-V) node. People with Wolff-Parkinson-White syndrome have an additional tissue bridge between the atria and the ventricles that provides an alternative pathway for conduction of the electrical signal. The timing of the electrical signal to the ventricles is critical for the heart to beat properly and the A-V node acts as a gatekeeper between the atria and ventricles, modulating the spread of the electrical impulse. If the atria beat too quickly, not all signals will pass through the A-V node which ensures that the ventricles do not beat too fast. The extra conduction pathway found in people with Wolff-Parkinson-White syndrome lacks the special properties of the A-V node and can lead to very fast heart rhythms. It is also possible for the electrical signal to loop around between the atria and ventricles, entering via the A-V node and returning via the additional pathway. This leads to very fast ventricular contraction, which can precipitate fibrillation and sudden death.

  Fortunately, Wolff-Parkinson-White syndrome can now be easily cured by a very simple and successful operation in which a catheter is passed into the heart, the offending abnormal tissue bridge identified, and radio frequency pulses used to destroy it.

  The Electric Heart

  When a heart cell is stimulated it fires off an electrical impulse, or action potential. This spreads rapidly over the surface of the cell and then along a network of fine tubules that penetrate deep into the interior of the muscle fibre. The change in membrane potential to more positive values opens calcium channels within the surface and tubular membranes, so triggering an influx of calcium ions from the extracellular solution. In turn, these serve as intracellular messengers that cause the release of a much larger number of calcium ions from a series of intracellular stores. Interaction of calcium ions with the contractile proteins then causes the muscle cell to shorten. In effect, the electrical impulse is a way of ensuring that calcium increases simultaneously throughout the cell, so that each heart muscle fibre contracts smoothly and synchronously.

  As in the case of nerve cells, ion channels are responsible for the electrical impulses of heart cells. However, many more types of channel are involved in shaping the action potential of the heart. It is initiated by the opening of sodium channels. These channels are similar, but not identical to those of nerve cells, which explains why fatal poisons like that of the puffer fish block electrical impulses in the nerves, but not the heart. Errors in the gene coding for the cardiac sodium channel gene (SCN5A) can result in abnormal sodium channels that do not function properly. This gives rise to a rare inherited condition called Brugada syndrome, which disrupts the electrical activity of the heart without warning and can cause sudden death.

  Brugada syndrome is most common in the Asian community. It accounts for around 12 per cent of unexplained deaths and – apart from accidents – is the leading cause of death of men under the age of forty in certain regions of the world. Indeed, it is so common in the Philippines that it has a special name – bangungut, which means ‘to rise and moan in sleep’. An increased incidence of unexpected death while sleeping is also found in Japan and Thailand (where it is known as Lai Tai, ‘death during sleep’). Intriguingly, the disease is far more common in men than women. Perhaps this is why in Thailand it was believed, erroneously, that the disorder could be averted by sleeping in women’s clothing. Local superstition has it that young men died because they were snatched away by a widow ghost, who could be tricked into thinking her potential victim was female by their dress. As the ghost was not interested in women, they would escape death.

  Understanding the genetic basis of Brugada syndrome came about because of a chance encounter between two scientists who happened to be seated next to one another on the bus ride to the airport following a conference on the heart. When Charles Antzelevitch expressed surprise that no patients had been found with a particular kind of cardiac arrhythmia, his companion informed him that in fact the Brugada brothers had recently described such a rare condition. This fortuitous meeting led to the discovery that Brugada syndrome is caused by loss-of-function mutations in the cardiac sodium channel gene. As many as fifty different mutations are now known to cause the disease. The higher incidence of these mutations in South Asian populations explains the greater prevalence of Brugada syndrome.

  Opening of the sodium channel pores is quickly followed by the opening of calcium channels, which enables calcium ions to flood into the cell, where they trigger the release of stored calcium and thereby contraction. The importance of calcium ions for the contraction of the heart was discovered serendipitously by Sydney Ringer in the early 1880s. Ringer was searching for a solution that enabled him to maintain the normal beating of a frog’s heart. He did this by adding known amounts of inorganic salts to distilled water, which contains no ions at all. Or so he thought. In fact, because Ringer had a busy life as a medical doctor, the solutions were prepared by his technician, who did not always follow instructions precisely. Ringer’s first paper states that only sodium and potassium ions were needed to maintain cardiac contraction. But as he subsequently wrote, ‘After the publication’ (of his previous paper), ‘I discovered, that the saline solution which I had used had not been prepared with distilled water but with pipe water supplied by the New River Water Company. As this water contains minute traces of various inorganic substances, I at once tested the action of saline solution made with distilled water and I found that I did not get the effects described in the paper referred to. It is obvious therefore that the effects I had obtained are due to some of the inorganic constituents of the pipe water.’ It turned out that the missing ingredient was calcium – or ‘lime’ as Ringer called i
t. One wonders if he praised or castigated his lab technician (probably both).

  Calcium channels are not just important for letting in the calcium ions that trigger the release of stored calcium. The fact that they close (inactivate) only slowly at positive membrane potentials helps prolong the cardiac action potential, thereby providing more time for the heart to contract. The action potential of a ventricular cell is about half a second long, almost 500 times longer than that of a nerve cell.

  The end of the cardiac action potential is produced by opening of potassium channels, and the resulting efflux of potassium ions returns the voltage gradient across the membrane to its resting value. As a consequence, the calcium channels shut, preventing calcium influx, so that the heart relaxes. Unlike those of nerve cells, many cardiac potassium channels take a long time to open, which helps ensure that the duration of the action potential in the heart is much longer. They also come in several flavours. One of the most important is known as HERG. Its strange name derives from its close relationship to an ion channel in the fruit fly Drosophila. This tiny insect is much beloved by geneticists because it has a very fast life cycle, breeds prodigiously, and many genetic mutants have been identified. As flies rarely stay still long enough to be studied, they are usually anaesthetized with ether. In the 1960s, when go-go dancing was all the rage, a mutant fly was found that shook its legs and span around when exposed to ether, and consequently it was christened ether-á-go-go or EAG for short. Soon after, a related channel was found in the heart and it was named, rather less imaginatively, the ether-á-go-go-related channel or ERG. The human channel thus became HERG.