The Spark of Life: Electricity in the Human Body (20 page)

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 donated 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 it. 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.

Frightened to Death

Alex’s unexpected collapse one morning from sudden cardiac arrhythmia occurred because she carries a rare mutation in her HERG potassium channel that renders it non-functional. Because these channels are important for ending the cardiac action potential, their loss increases the action potential duration, giving rise to a longer QT interval in the electrocardiogram. For obvious reasons this disease is called long QT (LQT) syndrome. The increase in the QT interval is sometimes very small, a mere 2 to 5 per cent, but it can be sufficient to precipitate a cardiac arrhythmia known as ‘torsade de pointes’. The name, which means ‘twisting of the points’, is taken from a ballet move and describes the distorted form of the ECG. When this happens, the heart no longer pumps blood as effectively and the brain is rapidly deprived of oxygen, which may cause abrupt loss of consciousness. This explains why patients with this condition are prone to sudden blackouts. In some cases, the abnormal electrical activity degenerates into ventricular fibrillation, which can be fatal.

Symptoms of LQT syndrome usually first appear in the pre-teen or teenage years. They are often precipitated by stress, such as exercise, fear or excitement. People have collapsed while running for a bus, diving into a swimming pool, playing in a baseball game, or participating in a TV quiz show. There is usually no warning. Most individuals do not complain of feeling faint or dizzy beforehand; they just abruptly lose consciousness. In about a third of fatal attacks, the person appeared quite fit and healthy before they collapsed, and some people have died while asleep or when aroused abruptly from sleep by the ringing of an alarm clock. Sudden cardiac death was even recognized by Hippocrates, who commented, ‘those who suffer from frequent and strong faints without any obvious cause die suddenly’.

Some mutations are particularly severe because they cause deafness as well as cardiac problems: this is because the ion channel concerned is also found in the ear, where it is involved in hearing. An early account of a fatal attack in a patient with this syndrome was given by Meissner in 1856. He vividly described how a young deaf–mute girl who attended the Leipzig Institute collapsed and died while being publically admonished for stealing a small item. Her death made a marked impression on the other children, who saw it as divine punishment for her misdemeanour. When her parents were informed, they were not surprised. It turned out that there had been similar tragic incidents in the family beforehand – one child had fallen down dead after sudden shock, and another after a terrible tantrum.

The death of a young child is a heartbreaking event but it is especially devastating when a seemingly healthy baby unexpectedly dies while asleep. In such circumstances, foul play may be suspected, adding to the agony, and it is not unknown for cot death to result in prosecution of the parents and a murder conviction. Even when this is not the case, not knowing the cause of your child’s death can be a lifelong burden. Recently, it has been found that some cot death victims carried ion channel mutations that predisposed them to LQT syndrome, suggesting that they may have died of sudden cardiac death. Just how many cases of cot death are caused from heart arrhythmias precipitated by defective ion channels is still unclear. Nevertheless, post-mortem screening for ion channel mutations would seem a good idea, not only to help identify the cause of death, but also because of the possibility that other family members may be asymptomatic carriers of any mutation identified and thus potentially at risk.