Wednesday, 9 April 2014

A brief history of electrocardiography.

Find out how electrocuting chickens (1775), getting laboratory assistants to put their hands in buckets of saline (1887), taking the ECG of a horses and then observing their open heart surgey (1912), induction of indiscriminate angina attacks (1931), and hypothermic dogs (1953) have helped to improve our understanding of the ECG as a clinical tool. And why is the ECG labelled PQRST (1895)?

17th and 18th Centuries The harnessing of electricity, observations of its effects on animal tissues and the discovery of 'animal electricity'.

William Gilbert
William Gilbert, Physician to Queen Elizabeth I, President of the College of Physicians (before its Royal Charter), and creator of the 'magnetic philosophy' introduces the term 'electrica' for objects (insulators) that hold static electricity. He derived the word from the Greek for amber (electra). It was known from ancient times that amber when rubbed could lift light materials. Gilbert added other examples such as sulphur and was describing what would later be known as 'static electricity' to distinguish it from the more noble magnetic force which he saw as part of a philosophy to destroy forever the prevailing Aristotlean view of matter. Gilbert W. De Magnete, magneticisique corporibus, et de magno magnete tellure. [On the Magnet, Magnetic Bodies, and the Great Magnet of the Earth] 1600
Sir Thomas Browne, Physician, whilst writing to dispel popular ignorance in many matters, is the first to use the word 'electricity'. Browne calls the attractive force "Electricity, that is, a power to attract strawes or light bodies, and convert the needle freely placed". (He is also the first to use the word 'computer' - referring to people who compute calendars.) Browne, Sir Thomas. Pseudodoxia Epidemica: Or, enquiries Into Very Many Received Tenents, and Commonly Presumed Truths. 1646: Bk II, Ch. 1. London
Otto Von Guericke builds the first static electricity generator.

Descarte's reflex ©BIU
The work of Rene Descartes, French Philosopher, is published (after his death) and explains human movement in terms of the complex mechanical interaction of threads, pores, passages and 'animal spirits'. He had worked on his ideas in the 1630s but had abandoned publication because of the persecution of other radical thinkers such as Galileo. William Harvey had developed similar ideas but they were never published. Descartes R. De Homine (Treatise of Man); 1662: Moyardum & leffen, Leiden.
Jan Swammerdam, a Dutchman, disproves Descartes' mechanistic theory of animal motion by removing the heart of a living frog and showing that it was still able to swim. On removing the brain all movement stopped (which would be in keeping with Descarte's theory) but then, when the frog was dissected and a severed nerve end stimulated with a scalpel the muscles twitched. This proved that movement of a muscle could occur without any connection to the brain and therefore the transmission of 'animal spirits' was not necessary. Swammerdam's ideas were not widely known and his work was not published until after his death. However, he wrote many letters and his friend, Nicolaus Steno, did attack the Cartesian ideas in a lecture in Paris in 1665. Boerhaave published Swammerdam's 'Book of Nature' in the 1730s which was translated into English in 1758.

electrical stimulation? ©BIU
Swammerdam refines his experiments on muscle contraction and nerve conduction and demonstrated some to notable figures such as the Grand-Duke Cosimo of Tuscany who was visiting Swammerdam's father's house on the Oude Schans in Amsterdam. One experiment suspended the muscle on a brass hook inside a glass tube with a water droplet to detect movement and 'irritated' the nerve with a silver wire. This produced movement of the muscle and it may have been due to the induction of a small electrical charge - although Swammerdam would have been unaware of this. In the diagram opposite - a) glass tube, b) muscle, c) sliver wire, d) brass wire, e) drop of water, f) investigator's hand.
Stephen Gray, English scientist, distinguishes between conductors and insulators of electricity. He demonstrates the transfer of static electrical charge to a cork ball across 150 metres of wet hemp thread. Later he found that the transfer could be achieved over greater distances by using brass wire.

Leyden Jar
Dutch physicist Pieter van Musschenbroek discovers that a partly filled jar with a nail projecting from a cork in its neck can store an electrical charge. The jar is named the 'Leyden Jar' after the place of its discovery. Ewald Georg von Kliest of Pomerania invented the same device independently. Using a Leyden jar in 1746, Jean-Antoine Nollet, French physicist and tutor to the Royal family of France sends an electrical current through 180 Royal Guards during a demonstration to King Louis XV.
Edward Bancroft, an American Scientist, suggests that the 'shock' from the Torpedo Fish is electrical rather than mechanical in nature. He showed that the properties of the shock were similar to those from a Leyden jar in that it could be conducted or insulated with appropriate materials. The Torpedo fish and other species were widely known to deliver shocks and were often used in this way for therapeutic reasons. However, electrical theory at the time dictated that electricity would always flow through conductors and diffuse away from areas of high charge to low charge. Since living tissues were known to be conductors it was impossible to imagine how an imbalance of charge could exist within an animal and therefore animals could not use electricity for nerve conduction - or to deliver shocks. Furthermore, 'water and electricity do not mix' so the idea of an 'electric fish' was generally not accepted. Bancroft, E. An essay on the natural history of Guiana, London:T. Becket and P. A. de Hondt, 1769.

John Walsh
John Walsh, fellow of the Royal Society and Member of Parliament, obtains a visible spark from an electric eel Electrophorus electricus. The eel was out of water as it was not possible to produce the spark otherwise. He used thin strips of tin foil and demonstrated his technique to many colleagues and visitors at his house in London. Unfortunately he never published his eel experiment though he did win the Copley medal in 1774 and 1783 for his work. The observations of Walsh, and Bancroft before him, added to the argument that some form of animal electricity existed. Walsh, J. On the electric property of torpedo: in a letter to Ben. Franklin. Phil. Trans. Royal Soc. 1773;63:478-489
The Rev. Mr Sowdon and Mr Hawes, apothecary, report on the surprising effects of electricity in a case report of recovery from sudden death published in the annual report of the newly founded Humane Society now the Royal Humane Society. The Society had developed from 'The Institution for Affording immediate relief to persons apparently dead from drowning'. It was "instituted in the year 1774, to protect the industrious from the fatal consequences of unforseen accidents; the young and inexperienced from being sacrificed to their recreations; and the unhappy victims of desponding melancholy and deliberate suicide; from the miserable consequences of self-destruction." A Mr Squires, of Wardour Street, Soho lived opposite the house from which a three year old girl, Catherine Sophia Greenhill had fallen from the first storey window on 16th July 1774. After the attending apothecary had declared that nothing could be done for the child Mr Squires, "with the consent of the parents very humanely tried the effects of electricity. At least twenty minutes had elapsed before he could apply the shock, which he gave to various parts of the body without any apparent success; but at length, upon transmitting a few shocks through the thorax, he perceived a small pulsation: soon after the child began to sigh, and to breathe, though with great difficulty. In about ten minutes she vomited: a kind of stupor, occaisioned by the depression of the cranium, remained for some days, but proper means being used, the child was restored to perfect health and spirits in about a week.
"Mr. Squires gave this astonishing case of recovery to the above gentlemen, from no other motive than a desire of promoting the good of mankind; and hopes for the future that no person will be given up for dead, till various means have been used for their recovery."
Since it is clear she sustained a head injury the electricity probably stimulated the child out of deep coma rather than providing cardiac defibrillation (see also 1788, Charles Kite). Annual Report 1774: Humane Society, London. pp 31-32
Abildgaard shows that hens can be made lifeless with electrical impulses and he could restore a pulse with electrical shocks across the chest. "With a shock to the head, the animal was rendered lifeless, and arose with a second shock to the chest; however, after the experiment was repeated rather often, the hen was completely stunned, walked with some difficulty, and did not eat for a day and night; then later it was very well and even laid an egg." Abildgaard, Peter Christian. Tentamina electrica in animalibus. Inst Soc Med Havn. 1775; 2:157-61.

Luigi Galvani
Italian Anatomist Luigi Galvani notes that a dissected frog's leg twitches when touched with a metal scalpel. He had been studying the effects of electricity on animal tissues that summer. On 20th September 1786 he wrote "I had dissected and prepared a frog in the usual way and while I was attending to something else I laid it on a table on which stood an electrical machine at some distance from its conductor and separated from it by a considerable space. Now when one of the persons present touched accidentally and lightly the inner crural nerves of the frog with the point of a scalpel, all the muscles of the legs seemed to contract again and again as if they were affected by powerful cramps."
He later showed that direct contact with the electrical generator or the ground through an electrical conductor would lead to a muscle contraction. Galvani also used brass hooks that attached to the frog's spinal cord and were suspended from an iron railing in a part of his garden. He noticed that the frogs' legs twitched during lightening storms and also when the weather was fine. He interperated these results in terms of "animal electricity" or the preservation in the animal of "nerveo-electrical fluid" similar to that of an electric eel. He later also showed that electrical stimulation of a frog's heart leads to cardiac muscular contraction. Galvani. De viribus Electritatis in motu musculari Commentarius. 1791
Galvani's name is given to the 'galvanometer' which is an instrument for measuring (and recording) electricity - this is essentially what an ECG is; a sensitive galvanometer.
Charles Kite wins the Silver Medal of the Humane Society (awarded at the first Prize Medal ceremony of the Society co-judged with the Medical Society of London) with an essay on the use of electricity in the diagnosis and resuscitation of persons apparently dead. This essay is often cited as the first record of cardiac defibrillation but the use of electricity suggested by Mr Kite is much different. For example, on describing a case of drowning from 1785 where resuscitation had been attempted with artificial respiration, warmth, tobacco, "volatiles thrown into the stomach, frictions, and various lesser stimuli" for nearly an hour, he then recalls the use of electricity. "Electricity was then applied, and shocks sent through in every possible direction; the muscles through which the fluid [electricity] passed were thrown into strong contractions." He concluded that electricity was a valuable tool that could determine whether or not a person, apparently dead, could be successfully resuscitated. Annual Report 1788: Humane Society, London. pp 225-244. Kite C. An Essay on the Recovery of the Apparently Dead. 1788: C. Dilly, London.

Alessandro Volta
Alessandro Volta, Italian Scientist and inventor, attempts to disprove Galvani's theory of "animal electricity'" by showing that the electrical current is generated by the combination of two dissimilar metals. His assertion was that the electrical current came from the metals and not the animal tissues. (We now know that both Galvani and Volta were right.) To prove his theory he develops the voltaic pile in 1800 (a column of alternating metal discs - zinc with copper or silver - separated by paperboard soaked in saline) which can deliver a substantial and steady current of electricity. Enthusiasm in the use of electricity leads to further attempts at reanimation of the dead with experiments on recently hanged criminals. Giovani Aldini (the nephew of Galvani) conducts an experiment at the Royal College of Surgeons in London in 1803. The executed criminal had lain in a temperature of 30 F for one hour and was transported to the College. "On applying the conductors to the ear and to the rectum, such violent muscular contractions were executed, as almost to give the appearance of the reanimation". Aldini, J. Essai: Th�orique et exp�rimental sur le Galvanisme, Paris (1804), Giovani Aldini. General Views on the Application of Galvanism to Medical Purposes Principally in cases of suspended Animation (London: J. Callow, Princes Street and Burgess and Hill, Great Windmill Street, 1819). Mary Shelly's Frankenstein was published in 1818. Louis Figuier, Les merveilles de la Science (Paris, 1867), p.653
1800 to 1895 The design of sensitive instruments that could detect the small electrical currents in the heart.
While demonstrating to students the heating of a platinum wire with electricity from a voltaic pile at the University of Copenhagen, Danish physicist Hans Christian Oersted notices that a nearby magnetized compass needle moves each time the electrical current is turned on. He discovers electromagnetism which is given a theoretical basis (with remarkable speed) by Andr� Marie Amp�re.
Johann (Johan) Schweigger of Nuremberg increases the movement of magnetized needles in electromagnetic fields. He found that by wrapping the electric wire into a coil of 100 turns the effect on the needle was multiplied. He proposed that a magnetic field revolved around a wire carrying a current which was later proven by Michael Faraday. Schweigger had invented the first galvanometer and announced his discovery at the University of Halle on 16th September 1820.
Leopoldo Nobili, Professor of Physics at Florence, develops an 'astatic galvanometer'. Using two identical magnetic needles of opposite polarity, either fixed together with a figure of eight arrangment of wire loops (in earlier versions), or one moveable needle with a wire loop and one with a scale (in later versions), the effects of the earth's magnetic field could be compensated for. In 1827, using this instrument, he managed to detect the flow of current in the body of a frog from muscles to spinal cord. He detected the electricity running along saline moistened cotton thread joining the dissected frog's legs in one jar to its body in another jar. Nobili was working to support the theory of animal electricity and this conduction, transmitted without wires, he felt demonstrated animal electricity.

Carlo Matteucci
Carlo Matteucci, Professor of Physics at the University of Pisa, and student of Nobili, shows that an electric current accompanies each heart beat. He used a preparation known as a 'rheoscopic frog' in which the cut nerve of a frog's leg was used as the electical sensor and twitching of the muscle was used as the visual sign of electrical activity. He also used Nobili's astatic galvanometer for the study of electricity in muscles typically inserting one galvanometer wire in the open end of the dissected muscle and the other on the surface of the muscle. He went on to try and demonstrate conduction in nerve but was unable to do so (since his galvanometers were not sensitive enough). Matteucci C. Sur un phenomene physiologique produit par les muscles en contraction. Ann Chim Phys 1842;6:339-341
Dr Golding Bird, a Physician, accomplished chemist and member of the London Electrical Society, opens an electrical therapy room at Guy's Hospital, London treating a large range of diseases. Although the application of electricity was popular it was not considered a subject worthy of serious investigation. Because of Bird's reputation as a researcher electrical therapy achieved popularity amongst London Physicians including his mentor Dr Thomas Addison. Bird G. Lectures on Electricity and Galvanism, in their physiological and therapeutical relations, delivered at the Royal College of Physicians, in March, 1847 (Wilson & Ogilvy, London, 1847)

Emil Du bois-Reymond
German physiologist Emil Du bois-Reymond describes an "action potential" accompanying each muscular contraction. He detected the small voltage potential present in resting muscle and noted that this diminished with contraction of the muscle. To accomplish this he had developed one of the most sensitive galvanometers of his time. His device had a wire coil with over 24,000 turns - 5 km of wire. Du Bios Reymond devised a notation for his galvanometer which he called the 'disturbance curve'. "o" was the stable equilibrium point of the astatic galvanometer needle and p, q, r and s (and also k and h) were other points in its deflection. Du Bois-Reymond, E. Untersuchungen uber thierische Elektricitat. Reimer, Berlin: 1848.
H. Bence Jones, Physician at St George's Hospital, reports on the disappointing results of electrical therapy on his patients. He concluded that only four of his 23 cases seemed to improve. H. Bence Jones. Remedial Action of Electricity. Lond J Med Feb 1849; s2-1: 125 - 129; doi:10.1136/bmj.s2-1.2.125
Bizarre unregulated actions of the ventricles (later called ventricular fibrillation) is described by Hoffa during experiments with strong electrical currents across the hearts of dogs and cats. He demonstrated that a single electrical pulse can induce fibrillation. Hoffa M, Ludwig C. 1850. Einige neue versuche uber herzbewegung. Zeitschrift Rationelle Medizin, 9: 107-144
Rudolph von Koelliker and Heinrich Muller confirm that an electrical current accompanies each heart beat by applying a galvanometer to the base and apex of an exposed ventricle. They also applied a nerve-muscle preparation, similar to Matteucci's, to the ventricle and observed that a twitch of the muscle occured just prior to ventricular systole and also a much smaller twitch after systole. These twitches would later be recognised as caused by the electrical currents of the QRS and T waves. von Koelliker A, Muller H. Nachweis der negativen Schwankung des Muskelstroms am naturlich sich kontrahierenden Herzen. Verhandlungen der Physikalisch-Medizinischen Gesellschaft in Wurzberg. 1856;6:528-33.
William Thompson (Lord Kelvin), Professor of Natural Philosophy at Glasgow University, invents the 'mirror galvanometer' for the reception of transatlantic telegraph transmissions. A small, freely rotating mirror, with magents stuck to its back is suspended in a fine copper coil and a reflected spot of light from this mirror 'amplifies' the small movements when electrical current is present. The whole apparatus was suspended in an air chamber and the pressure inside could be adjusted to vary the damping seen on the signals. This galvanometer was sensitive enough for transatlantic telegraphy.
Thompson improves telegraph transmissions with the 'Siphon Recorder'. Before d'Arsonval (1880), Thompson uses a fine coil suspended in a strong magnetic magnetic field. Attached to the coil but isolated from it by ebonite (an insulator) was a siphon of ink. The siphon was charged with high voltage so that the ink was sprayed onto the paper that moved over an earthed metal surface. The siphon recorder could therefore not only detect currents it could also record them onto paper.
Alexander Muirhead, an electrical engineer and pioneer of telegraphy, may have a recorded a human electrocardiogram at St Bartholomew's Hospital, London but this is disputed. If he had he is thought to have used a Thompson Siphon Recorder. Elizabeth Muirhead, his wife, wrote a book of his life and claimed that he refrained from publishing his own work for fear of misleading others. Elizabeth Muirhead. Alexander Muirhead 1848 - 1920. Oxford, Blackwell: privately printed 1926.
French physicist Gabriel Lippmann invents a capillary electrometer. It is a thin glass tube with a column of mercury beneath sulphuric acid. The mercury meniscus moves with varying electrical potential and is observed through a microscope.
Mr Green, a surgeon, publishes a paper on the resuscitation of a series of patients who had suffered cardiac and / or respiratory arrest during anaesthesia with chloroform. He uses a galvanic pile (battery) of 200 cells generating 300 Volts which he applied to the patient as follows "One pole should be applied to the neck and the other to the lower rib on the left side." Green T. On death from chloroform: its prevention by galvanism. Br Med J 1872 1: 551-3. Although this has been reported as an example of cardiorespiratory resuscitation it is unclear what the exact mechanism seems to be. It is unlikely to be electric cardioversion or external pacing. It seems to be another example of electrophrenic stimulation (See also Duchenne 1872).

An 'electric' smile.
Guillaume Benjamin Amand Duchenne de Boulogne, pioneering neurophysiologist, describes the resuscitation of a drowned girl with electricity in the third edition of his textbook on the medical uses of electricity. This episode has sometimes been described as the first 'artificial pacemaker' but he used an electrical current to induce electrophrenic rather than myocardial stimulation. Duchenne GB. De l'electrisation localisee et de son application a la pathologie et la therapeutique par courants induits at par courants galvaniques interrompus et continus. [Localised electricity and its application to pathology and therapy by means of induced and galvanic currents, interrupted and continuous] 3ed. Paris. JB Bailliere et fils; 1872
Richard Caton, a Liverpool Physician, presents to the British Medical Association in July 1875 in Edinburgh. Using a Thompson 'mirror galvanometer' in animals he shows it was possible to detect 'feeble currents of varying direction ... when the electrodes are placed on two points of the external surface, or one electrode on the grey matter and one on the surface of the skull'. This is the first report of the EEG (or electroencephalogram). Caton was exploring another Physician's hypothesis, John Hughlings Jackson, who suggested in 1873 that epilepsy was due to excessive electrical activity in the grey matter of the brain. Caton R: The electric currents of the brain. Br Med J 1875; 2(765):278, Mumenthaler, Mattle Eds. Neurology. 4th Edition. Stuttgart, Thieme: 2004.
Marey uses the electrometer to record the electrical activity of an exposed frog's heart. Marey EJ. Des variations electriques des muscles et du couer en particulier etudies au moyen de l'electrometre de M Lippman. Compres Rendus Hebdomadaires des Seances de l'Acadamie des sciences 1876;82:975-977
British physiologists John Burden Sanderson and Frederick Page record the heart's electrical current with a capillary electrometer and shows it consists of two phases (later called QRS and T). Burdon Sanderson J. Experimental results relating to the rhythmical and excitatory motions of the ventricle of the frog. Proc R Soc Lond 1878;27:410-414
French physicist Ars�ne d'Arsonval in association with Marcel Deprez, improves the galvanometer. Instead of a magnetized needle moving when electrical current flows through a surrounding wire coil the Deprez-d'Arsonval galvanometer has a fixed magnet and moveable coil. If a pointer is attached to the coil it can move over a suitably calibrated scale. The d'Arsonval galvanometer is the basis for most modern galvanometers. Comptes rendus de l'Acad�mie des sciences, 1882, 94: 1347-1350
John Burden Sanderson and Frederick Page publish some of their recordings. Burdon Sanderson J, Page FJM. On the electrical phenomena of the excitatory process in the heart of the tortoise, as investigated photographically. J Physiol (London) 1884;4:327-338
British physiologist Augustus D. Waller of St Mary's Medical School, London publishes the first human electrocardiogram. It is recorded with a capilliary electrometer from Thomas Goswell, a technician in the laboratory. Waller AD. A demonstration on man of electromotive changes accompanying the heart's beat. J Physiol (London) 1887;8:229-234
Dutch physiologist Willem Einthoven sees Waller demonstrate his technique at the First International Congress of Physiologists in Bale. Waller often demonstrated by using his dog "Jimmy" who would patiently stand with paws in glass jars of saline.
Professor John McWilliam, of Aberdeen University, describes ventricular fibrillation as "unexpected, and irretrievable cardiac failure [which] may ... present itself in the form of an abrupt onset of fibrillar contraction ... The cardiac pump is thrown out of gear, and the last of its vital energy is dissipated in a violent and prolonged turmoil of fruitless activity in the ventricular walls." He also describes the electrical stimulation of the heart in cases of "fatal syncope" in man. "A single induction shock readily causes a beat in an inhibited heart, and a regular series of induction shocks (for example, sixty or seventy per minute) gives a regular series of heartbeats at the same rate." McWilliam JA. Cardiac Failure and Sudden Death. Br Med J 1889;1:6-8. McWilliam JA. Electrical stimulation of the heart in man. Br Med J 1889;1:348�50.
GJ Burch of Oxford devises an arithmetical correction for the observed (sluggish) fluctuations of the electrometer. This allows the true waveform to be seen but only after tedious calculations. Burch GJ. On a method of determining the value of rapid variations of a difference potential by means of a capillary electrometer. Proc R Soc Lond (Biol) 1890;48:89-93
British physiologists William Bayliss and Edward Starling of University College London improve the capillary electrometer. They connect the terminals to the right hand and to the skin over the apex beat and show a "triphasic variation accompanying (or rather preceding) each beat of the heart". These deflections are later called P, QRS and T. Bayliss WM, Starling EH. On the electrical variations of the heart in man. Proc Phys Soc (14th November) in J Physiol (London) 1891;13:lviii-lix and also On the electromotive phenomena of the mammalian heart. Proc R Soc Lond 1892;50:211-214 They also demonstrate a delay of about 0.13 seconds between atrial stimulation and ventricular depolarisation (later called PR interval). On the electromotive phenomena of the mammalian heart. Proc Phys Soc (21st March) in J Physiol (London) 1891;12:xx-xxi
Willem Einthoven introduces the term 'electrocardiogram' at a meeting of the Dutch Medical Association. (Later he claims that Waller was first to use the term). Einthoven W: Nieuwe methoden voor clinisch onderzoek [New methods for clinical investigation]. Ned T Geneesk 29 II: 263-286, 1893
1895 to date The first accurate recording of the electrocardiogram and its development as a clinical tool.
Einthoven, using an improved electrometer and a correction formula developed independently of Burch, distinguishes five deflections which he names P, Q, R, S and T. Einthoven W. Ueber die Form des menschlichen Electrocardiogramms. Arch f d Ges Physiol 1895;60:101-123
Why PQRST and not ABCDE? The four deflections prior to the correction formula were labelled ABCD and the 5 derived deflections were labelled PQRST. The choice of P is a mathematical convention dating from Descartes (as used also by Du Bois-Reymond in his galvanometer's 'disturbance curve' 50 years previously) by using letters from the second half of the alphabet. N has other meanings in mathematics and O is used for the origin of the Cartesian coordinates. In fact Einthoven used O ..... X to mark the timeline on his diagrams. P is simply the next letter. A lot of work had been undertaken to reveal the true electrical waveform of the ECG by eliminating the damping effect of the moving parts in the amplifiers and using correction formulae. If you look at the diagram in Einthoven's 1895 paper you will see how close it is to the string galvanometer recordings and the electrocardiograms we see today. The image of the PQRST diagram may have been striking enough to have been adopted by the researchers as a true representation of the underlying form. It would have then been logical to continue the same naming convention when the more advanced string galvanometer started creating electrocardiograms a few years later. (For more on Descartes see Henson JR. Descartes and the ECG lettering series. J Hist Med Allied Sci. April 1971;181�186)
Clement Ader, a French electrical engineer, reports his amplification system for detecting Morse code signals transmitted along undersea telegraph lines. It was never intended to be used as a galvanometer. Einthoven later quoted Ader's work but seems to have developed his own amplification device independently. Ader C. Sur un nouvel appareil enregistreur pour cables sous-marins. C R Acad Sci (Paris) 1897;124:1440-1442

Karel Wenkebach
Karel Frederik Wenckebach publishes a paper "On the analysis of irregular pulses" describing impairment of AV conduction leading to progressive lengthening and blockage of AV conduction in frogs. This will later be called Wenckebach block (Mobitz type I) or Wenckebach phenomenon.
Jean-Louis Prevost, Professor of Biochemistry, and Frederic Batelli, Professor of Physiology, both of Geneva discover that large electrical voltages applied across an animal's heart can stop ventricular fibrillation. Prevost JL, Batelli F. Sur quelques effets des descharges electriques sur le coeur des mammiferes. [On the effects of electric shocks on the hearts of mammals.] Acad. Sci. Paris, FR.: 1899; 129:1267-1268.. They also report that ventricular fibrillation can be induced by small voltages (40 V). Prevost JL, Batelli F. La Mort Par Les Descharges Electriques. [Death by electrical disharges]. Journ. de Physiol. 1899;1:1085-99.
Einthoven invents a new galvanometer for producing electrocardiograms using a fine quartz string coated in silver based on ideas by Deprez and d'Arsonval (who used a wire coil). His "string galvanometer" weighs 600 pounds. Einthoven acknowledged the similar system by Ader but later (1909) calculated that his galvanometer was in fact many thousands of times more sensitive. Einthoven W. Un nouveau galvanometre. Arch Neerl Sc Ex Nat 1901;6:625-633
Einthoven publishes the first electrocardiogram recorded on a string galvanometer. Einthoven W. Galvanometrische registratie van het menschilijk electrocardiogram. In: Herinneringsbundel Professor S. S. Rosenstein. Leiden: Eduard Ijdo, 1902:101-107
Einthoven discusses commercial production of a string galvanometer with Max Edelmann of Munich and Horace Darwin of Cambridge Scientific Instruments Company of London.
Einthoven starts transmitting electrocardiograms from the hospital to his laboratory 1.5 km away via telephone cables. On March 22nd the first 'telecardiogram' is recorded from a healthy and vigorous man and the tall R waves are attributed to his cycling from laboratory to hospital for the recording.
John Hay of Liverpool, publishes pressure recordings from a 65 year old man showing heart block in which AV conduction did not seem to be impaired since the a-c intervals on the jugular venous waves was unchanged in the conducted beats. This is the first demonstration of what we now call Mobitz type II AV block. Hay J. Bradycardia and cardiac arrhythmias produced by depression of certain functions of the heart. Lancet 1906;1:138-143.
Einthoven publishes the first organised presentation of normal and abnormal electrocardiograms recorded with a string galvanometer. Left and right ventricular hypertrophy, left and right atrial hypertrophy, the U wave (for the first time), notching of the QRS, ventricular premature beats, ventricular bigeminy, atrial flutter and complete heart block are all described. Einthoven W. Le telecardiogramme. Arch Int de Physiol 1906;4:132-164 (translated into English. Am Heart J 1957;53:602-615)
Cremer records the first oesophageal electrocardiogram which he achieved with the help of a professional sword swallower. Oesophageal electrocardiography later developed in the 1970s to help differentiate atrial arrhythmias. He also records the first fetal electrocardiogram from the abdominal surface of a pregnant woman. Cremer. Ueber die direkte Ableitung der Aktionstr�me des menslichen Herzens vom Oesophagus und �ber das Elektrokardiogramm des F�tus. Munch. Med. Wochenschr. 1906;53:811
Arthur Cushny, professor of pharmacology at University College London, publishes the first case report of atrial fibrillation. His patient was 3 days post-op following surgery on an "ovarian fibroid" when she developed a "very irregular" pulse at a rate of 120 - 160 bpm. Her pulse was recorded with a "Jacques sphygmochronograph" which shows the radial pulse pressure against time - much like the arterial line blood pressure recordings used in Intensive Care today. Cushny AR, Edmunds CW. Paroxysmal irregularity of the heart and auricular fibrillation. Am J Med Sci 1907;133:66-77.
Edward Schafer of the University of Edinburgh is the first to buy a string galvanometer for clinical use.
Thomas Lewis of University College Hospital, London buys a string galvanometer and so does Alfred Cohn of Mt Sinae Hospital, New York.
Nicolai and Simmons report on the changes to the electrocardiogram during angina pectoris. Nicolai DF, Simons A. (1909) Zur klinik des elektrokardiogramms. Med Kiln 5;160
Walter James, Columbia University and Horatio Williams, Cornell University Medical College, New York publish the first American review of electrocardiography. It describes ventricular hypertrophy, atrial and ventricular ectopics, atrial fibrillation and ventricular fibrillation. The recordings were sent from the wards to the electrocardiogram room by a system of cables. There is a great picture of a patient having an electrocardiogram recorded with the caption "The electrodes in use".James WB, Williams HB. The electrocardiogram in clinical medicine. Am J Med Sci 1910;140:408-421, 644-669
Thomas Lewis publishes a classic textbook. The mechanism of the heart beat. London: Shaw & Sons and dedicates it to Willem Einthoven.
Thomas Lewis publishes a paper in the BMJ detailing his careful clinical and electrocardiographic observations of atrial fibrillation. Lewis describes how he and a colleague, Dr Woordruff a vet, identified the condition in horses and, at a later date, witnessed the fibrillating heart of a horse on Bulford Plain. "The chest was opened while the heart was still beating, and I obtained, as did those with me, a clear view of a fibrillating auricle, brought to this state, not by experimental interference, but by disease." Lewis T. A Lecture ON THE EVIDENCES OF AURICULAR FIBRILLATION, TREATED HISTORICALLY: Delivered at University College Hospital. Br Med J 1912;1:57-60.
Einthoven addresses the Chelsea Clinical Society in London and describes an equilateral triangle formed by his standard leads I, II and III later called 'Einthoven's triangle'. This is the first reference in an English article I have seen to the abbreviation 'EKG'.Einthoven W. The different forms of the human electrocardiogram and their signification. Lancet 1912(1):853-861
Bousfield describes the spontaneous changes in the electrocardiogram during angina. Bousfield G. Angina pectoris: changes in electrocardiogram during paroxysm. Lancet 1918;2:475
Hubert Mann of the Cardiographic Laboratory, Mount Sinai Hospital, describes the derivation of a 'monocardiogram' later to be called 'vectorcardiogram'. Mann H. A method of analyzing the electrocardiogram. Arch Int Med 1920;25:283-294
Harold Pardee, New York, publishes the first electrocardiogram of an acute myocardial infarction in a human and describes the T wave as being tall and "starts from a point well up on the descent of the R wave". Pardee HEB. An electrocardiographic sign of coronary artery obstruction. Arch Int Med 1920;26:244-257
Willem Einthoven wins the Nobel prize for inventing the electrocardiograph.
Woldemar Mobitz publishes his classification of heart blocks (Mobitz type I and type II) based on the electrocardiogram and jugular venous pulse waveform findings in patients with second degree heart block. Mobitz W. Uber die unvollstandige Storung der Erregungsuberleitung zwischen Vorhof und Kammer des menschlichen Herzens. (Concerning partial block of conduction between the atria and ventricles of the human heart). Z Ges Exp Med 1924;41:180-237.
A doctor from the Crown Street Women's Hospital in Sydney, who wished to remain anonymous, resuscitates a new-born baby with an electrical device later called a 'pacemaker'. The doctor wanted to remain anoymous because of the controversy surrounding research that artificially extended human life.
Ernstine and Levine report the use of vacuum-tubes to amplify the electrocardiogram instead of the mechanical amplification of the string galvanometer. Ernstine AC, Levine SA. A comparison of records taken with the Einthoven string galvanomter and the amplifier-type electrocardiograph. Am Heart J 1928;4:725-731
Frank Sanborn's company (founded 1917 and acquired by Hewlett-Packard in 1961 and since 1999, Philips Medical Systems) converts their table model electrocardiogram machine into their first portable version weighing 50 pounds and powered by a 6-volt automobile battery.
Sydney doctor Mark Lidwill, physician, and Edgar Booth, physicist, report the electrical resuscitation of the heart to a meeting in Sydney. Their portable device uses an electrode on the skin and a transthoracic catheter. Edgar Booth's design could deliver a variable voltage and rate and was employed to deliver 16 volts to the ventricles of a stillborn infant. Lidwell M C, "Cardiac Disease in Relation to Anaesthesia" in Transactions of the Third Session, Australasian Medical Congress, Sydney, Australia, Sept. 2-7 1929, p 160.
Wolff, Parkinson and White report an electrocardiographic syndrome of short PR interval, wide QRS and paroxysmal tachycardias. Wolff L, Parkinson J, White PD. Bundle branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia. Am Heart J 1930;5:685. Later, when other published case reports were examined for evidence of pre-excitation, examples of 'Wolff Parkinson White' syndrome were identified which had not been recognised as a clinical entity at the time. The earliest example was published by Hoffmann in 1909. Von Knorre GH. The earliest published electrocardiogram showing ventricular preexcitation. Pacing Clin Electrophysiol. 2005 Mar;28(3):228-30
Sanders first describes infarction of the right ventricle. Sanders, A.O. Coronary thrombosis with complete heart block and relative ventricular tachycardia: a case report, American Heart Journal 1930;6:820-823.
Charles Wolferth and Francis Wood describe the use of exercise to provoke attacks of angina pectoris. They investigated the ECG changes in normal subjects and those with angina but dismissed the technique as too dangerous "to induce anginal attacks indiscriminately". Wood FC, Wolferth CC, Livezey MM. Angina pectoris. Archives Internal Medicine 1931;47:339

first patented pacemaker
Dr Albert Hyman patents the first 'artificial cardiac pacemaker' which stimulates the heart by using a transthoracic needle. His aim was to produce a device that was small enough to fit in a doctor's bag and stimulate the right atrial area of the heart with a suitably insulated needle. His experiments were on animals. His original machine was powered by a crankshaft (it was later prototyped by a German company but was never successful). "By March 1, 1932 the artificial pacemaker had been used about 43 times, with a successful outcome in 14 cases." It was not until 1942 that a report of its successful short term use in Stokes-Adams attacks was presented. Hyman AS. Resuscitation of the stopped heart by intracardial therapy. Arch Intern Med. 1932;50:283
Goldhammer and Scherf propose the use of the electrocardiogram after moderate exercise as an aid to the diagnosis of coronary insufficiency. Goldhammer S, Scherf D. Elektrokardiographische untersuchungen bei kranken mit angina pectoris. Z Klin Med 1932;122:134
Charles Wolferth and Francis Wood describe the clinical use of chest leads. Wolferth CC, Wood FC. The electrocardiographic diagnosis of coronary occlusion by the use of chest leads. Am J Med Sci 1932;183:30-35
By joining the wires from the right arm, left arm and left foot with 5000 Ohm resistors Frank Wilson defines an 'indifferent electrode' later called the 'Wilson Central Terminal'. The combined lead acts as an earth and is attached to the negative terminal of the ECG. An electrode attached to the positive terminal then becomes 'unipolar' and can be placed anywhere on the body. Wilson defines the unipolar limb leads VR, VL and VF where 'V' stands for voltage (the voltage seen at the site of the unipolar electrode). Wilson NF, Johnston FE, Macleod AG, Barker PS. Electrocardiograms that represent the potential variations of a single electrode. Am Heart J. 1934;9:447-458.
McGinn and White describe the changes to the electrocardiogram during acute pulmonary embolism including the S1 Q3 T3 pattern. McGinn S, White PD. Acute cor pulmonale resulting from pulmonary embolism: its clinical recognition. JAMA 1935;114:1473.
American Heart Association and the Cardiac Society of Great Britain define the standard positions, and wiring, of the chest leads V1 - V6. The 'V' stands for voltage. Barnes AR, Pardee HEB, White PD. et al. Standardization of precordial leads. Am Heart J 1938;15:235-239
Tomaszewski notes changes to the electrocardiogram in a man who died of hypothermia. Tomaszewski W. Changements electrocardiographiques observes chez un homme mort de froid. Arch Mal Coeur 1938;31:525.
Langendorf reports a case of atrial infarction discovered at autopsy which, in retrospect, could have been diagnosed by changes on the ECG. Langendorf R. Elektrokardiogramm bei Vorhof-Infarkt. Acta Med Scand. 1939;100:136.
Emanuel Goldberger increases the voltage of Wilson's unipolar leads by 50% and creates the augmented limb leads aVR, aVL and aVF. When added to Einthoven's three limb leads and the six chest leads we arrive at the 12-lead electrocardiogram that is used today.
Arthur Master, standardises the two step exercise test (now known as the Master two-step) for cardiac function. Master AM, Friedman R, Dack S. The electrocardiogram after standard exercise as a functional test of the heart. Am Heart J. 1942;24:777
Young and Koenig report deviation of the P-R segment in a series of patients with atrial infarction. Young EW, Koenig BS. Auricular infarction. Am Heart J. 1944;28:287.
Gouaux and Ashman describe an observation that helps differentiate aberrant conduction from ventricular tachycardia. The 'Ashman phenomenon' occurs when a stimulus falls during the relative or absolute refractory period of the ventricles and the aberrancy is more pronounced. In atrial fibrillation with aberrant conduction this is demonstrated when the broader complexes are seen terminating a relatively short cycle that follows a relatively long one. The QRS terminating the shorter cycle is conducted 'more aberrantly' because it falls in the refractory period. The aberrancy is usually of a RBBB pattern. Gouaux JL, Ashman R. Auricular fibrillation with aberration simulating ventricular paroxysmal tachycardia. Am Heart J 1947;34:366-73.
Claude Beck, a pioneering cardiovascular surgeon in Cleveland, successfully defibrillates a human heart during cardiac surgery. The patient is a 14 year old boy - 6 other patients had failed to respond to the defibrillator. His prototype defibrillator followed experiments on defibrillation in animals performed by Carl J. Wiggers, Professor of Physiology at the Western Reserve University. Beck CS, Pritchard WH, Feil SA: Ventricular fibrillation of long duration abolished by electric shock. JAMA 1947; 135: 985-989.
Wiggers CJ, Wegria R. Ventricular fibrillation due to single localized induction in condenser shock supplied during the vulnerable phase of ventricular systole. Am J Physiol 1939;128:500
Rune Elmqvist, Swedish engineer who had trained as a doctor but never practiced, introduces the first ink jet printer for the transcription of analog physiological signals. He demonstrates its use in the recording of ECGs at the First International Congress of Cardiology in Paris in 1950. The machine (the mingograph) was developed by him at the company that later became Siemens. (Luderitz, 2002)

modern 'Holter' Monitor
Montana physician Norman Jeff Holter develops a 75 pound backpack that can record the ECG of the wearer and transmit the signal. His system, the Holter Monitor, is later greatly reduced in size, combined with tape / digital recording and used to record ambulatory ECGs. Holter NJ, Generelli JA. Remote recording of physiologic data by radio. Rocky Mountain Med J. 1949;747-751.
Sokolow and Lyon propose diagnostic criteria for left ventricular hypertrophy i.e. LVH is present if the sum of the size of the S wave in V1 plus the R wave in V6 exceeds 35 mm. Sokolow M, Lyon TP. The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J 1949;37:161
John Hopps, a Canadian electrical engineer and researcher for the National Research Council, together with two physicians (Wilfred Bigelow, MD of the University of Toronto and his trainee, John C. Callaghan, MD) show that a coordinated heart muscle contraction can be stimulated by an electrical impulse delivered to the sino-atrial node. The apparatus, the first cardiac pacemaker, measures 30cm, runs on vacuum tubes and is powered by household 60Hz electrical current. Bigelow WG, Callaghan JC, Hopps JA. "General hypothermia for experimental intracardiac surgery." Ann Surg 1950; 1132: 531-539.
Osborn, whilst experimenting with hypothermic dogs, describes the prominent J (junctional) wave which has often been known as the "Osborn wave". He found the dogs were more likely to survive if they had an infusion of bicarbonate and supposed the J wave was due to an injury current caused by acidosis. Osborn JJ. Experimental hypothermia: respiratory and blood pH changes in relation to cardiac function. Am J Physiol 1953;175:389.
Richard Langendorf publishes the "rule of bigeminy" whereby ventricular bigeminy tends to perpetuate itself. Langendorf R, Pick A, Winternitz M. Mechanisms of intermittent ventricular bigeminy. I. Appearence of ectopic beats dependent upon the length of the ventricular cycle, the "rule of bigeminy." circulation 1955;11:442.
Paul Zoll, a cardiologist, uses a more powerful defibrillator and performs closed-chest defibrillation in a human. Zoll PM, Linenthal AJ, Gibson P: Termination of Ventricular Fibrillation in Man by Externally Applied Countershock . NEJM 1956; 254: 727-729

long QT syndrome
Anton Jervell and Fred Lange-Nielsen of Oslo describe an autosomal recessive syndrome of long-QT interval, deafness and sudden death later known as the Jervell-Lange-Nielsen syndrome. Jervell A, Lange-Nielsen F. Congenital deaf mutism, functional heart disease with prolongation of the QT interval and sudden death. Am Heart J 1957;54:59.
Professor Ake Senning, of Sweden, places the first implantable cardiac pacemaker designed by Rune Elmqvist into a 43-year-old patient with complete heart block and syncope (Arne Larsson).
Myron Prinzmetal describes a variant form of angina in which the ST segment is elevated rather than depressed. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris. Am J Med 1959;27:374.
Smirk and Palmer highlight the risk of sudden death from ventricular fibrillation particularly when ventricular premature beats occur at the same time as the T wave. The 'R on T' phenomenon. Smirk FH, Palmer DG. A myocardial syndrome, with particular reference to the occurrence of sudden death and of premature systoles interrupting antecedent T waves. Am J Cardiol 1960;6:620.
Italian paediatrician C. Romano and Irish paediatrician O. Conor Ward (the following year) independently report an autosomal dominant syndrome of long-QT interval later known as the Romano-Ward syndrome. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell'eta pediatrica. Clin Pediatr. 1963;45:656-83.
Ward OC. New familial cardiac syndrome in children. J Irish Med Assoc. 1964;54:103-6

Excercise ECG
Robert Bruce and colleages describe their multistage treadmill exercise test later known as the Bruce Protocol. "You would never buy a used car without taking it out for a drive and seeing how the engine performed while it was running," Bruce says, "and the same is true for evaluating the function of the heart." Bruce RA, Blackman JR, Jones JW, Srait G. Exercise testing in adult normal subjects and cardiac patients. Pediatrics 1963;32:742
Bruce RA, McDonough JR. Stress testing in screening for cardiovascular disease. Bull. N.Y. Acad Med. 1969;45:1288
Baule and McFee are the first to detect the magnetocardiogram which is the electromagnetic field produced by the electrical activity of the heart. It is a method that can detect the ECG without the use of skin electrodes. Although potentially a useful technique it has never gained clinical acceptance, partly because of its greater expense. Baule GM, McFee R. Detection of the magnetic field of the heart. Am Heart J. 1963;66:95-96.
Mason and Likar modify the 12-lead ECG system for use during exercise testing. The right arm electrode is placed at a point in the infraclavicular fossa medial to the border of the deltoid muscle, 2 cm below the lower border of the clavicle. The left arm electrode is placed similarly on the left side. The left leg electrode is placed at the left iliac crest. Although this system reduces the variability in the ECG recording during exercise it is not exactly equivalent to the standard lead positions. The Mason-Likar lead system tends to distort the ECG with a rightward QRS axis shift, a reduction in R wave amplitude in lead I and aVL, and a significant increase in R wave amplitude in leads II, III and aVF. Eur Heart J. 1987 Jul;8(7):725-33

Torsade de pointes
Fran�ois Dessertenne of Paris publishes the first case of 'Torsade de pointes' Ventricular Tachycardia. Dessertenne F. La tachycardie ventriculaire a deux foyers opposes variables. Arch des Mal du Coeur 1966; 59:263
Journal of Electrocardiography, the Official Journal of the International Society for Computerized Electrocardiology and the International Society of Electrocardiology, is founded by Zao and Lepeschkin.
Henry Marriott introduces the Modified Chest Lead 1 (MCL1) for monitoring patients in Coronary Care.
Rosenbaum reviews the classification of ventricular premature beats and adds a benign form that arises from the right ventricle and is not associated with heart disease. This becomes known as the 'Rosenbaum ventricular extrasystole'. Rosenbaum MB. Classification of ventricular extrasystoles according to form. J Electrocardiol 1969;2:289.
Jay Cohn, of University of Minnesota Medical School, describes the 'syndrome of right ventricular dysfunction in the setting of acute inferior wall myocardial infarction'. Cohn JN, Guiha NH, Broder MI. Right ventricular infarction. Am J Cardiol 1974:33:209-214
Gozensky and Thorne introduce the term 'Rabbit ears' to electrocardiography. Rabbit ears describe the appearence of the QRS complex in lead V1 with an rSR' pattern (good rabbit) being typical of Right Bundle Branch Block and an RSr' (bad rabbit) suggesting a ventricular origin i.e. ventricular ectopy / tachycardia. Gozensky C, Thorne D. Rabbit ears: an aid in distinguishing ventricular ectopy from aberration. Heart Lung 1974;3:634.
Erhardt and colleagues describe the use of a right-sided precordial lead in the diagnosis of right ventricular infarction which had previously been thought to be electrocardiographically silent. Erhardt LR, Sjogrn A, Wahlberg I. Single right-sided precordial lead in the diagnosis of right ventricular involvement in inferior myocardial infarction. Am Heart J 1976;91:571-6
Dr Mieczyslaw (Michael) Mirowski and others file a US Patent "Circuit for monitoring a heart and for effecting cardioversion of a needy heart" (#4184493) which employs a transistor circuit that analyses the ECG signal using a probability density function. This allows an implantable defibrillator to detect when heart rhythm changes from normal (with steep QRS slopes) to abnormal ventriclar fibrillation. This development of machine-interpretation of the ECG is essential for the safe deployment of an automated defibrillator system and is reported in Circulation. Mirowski M, Mower MM, Langer A, Heilman MS, Schreibman J. A chronically implanted system for automatic defibrillation in active conscious dogs. Experimental model for treatment of sudden death from ventricular fibrillation. Circulation 1978;58:90-94.
Professor John Pope Boineau of Washington University School of Medicine publishes a 30-year percpective on the modern history of electrocardiography. Boineau JP. Electrocardiology: A 30-year Perspective. Ah Serendipity, My Fulsome Friend. Journal of Electrocardiology 21. Suppl (1988): S1-9

Brugada syndrome
Pedro Brugada and Josep brugada of Barcelona publish a series of 8 cases of sudden death, Right Bundle Branch Block pattern and ST elevation in V1 - V3 in apparently healthy individuals. This 'Brugada Syndrome' may account for 4-12% of unexpected sudden deaths and is the commonest cause of sudden cardiac death in individuals aged under 50 years in South Asia. The technology of the electrocardiogam, which is over 100 years old, can still be used to discover new clinical entities in cardiology. Brugada P, Brugada J. Right Bundle Branch Block, Persistent ST Segment Elevation and Sudden Cardiac Death: A Distinct Clinical and Electrocardiographic Syndrome. J Am Coll Cardiol 1992;20:1391-6
Cohen and He describe a new non-invasive approach to accurately map cardiac electrical activity by using the surface Laplacian map of the body surface electrical potentials. He B, Cohen RJ. Body surface Laplacian ECG mapping. IEEE Trans Biomed Eng 1992;39(11):1179-91

Mac 5000, 15-lead ECG
Robert Zalenski, Professor of Emergency Medicine, Wayne State University Detroit, and colleagues publish an influential article on the clinical use of the 15-lead ECG which routinely uses V4R, V8 and V9 in the diagnosis of acute coronary syndromes. Like the addition of the 6 standardised unipolar chest leads in 1938 these additional leads increase the sensitivity of the electrocardiogram in detecting myocardial infarction. Zalenski RJ, Cook D, Rydman R. Assessing the diagnostic value of an ECG containing leads V4R, V8, and V9: The 15-lead ECG. Ann Emerg Med 1993;22:786-793
Researchers from Texas show that 12-lead ECGs transmitted via wireless technology to hand-held computers is feasible and can be interpreted reliably by cardiologists. Pettis KS, Savona MR, Leibrandt PN et al. Evaluation of the efficacy of hand-held computer screens for cardiologists' interpretations of 12-lead electrocardiograms. Am Heart J. 1999 Oct;138(4 Pt 1):765-70
Physicians from the Mayo Clinic describe a new hereditary form of Short QT syndrome associated with syncope and sudden death that they discovered in 1999. Several genes have since been implicated. Gussak I, Brugada P, Brugada J, et al. Idiopathic short QT interval: a new clinical syndrome? Cardiology. 2000;94(2):99-102
Danish cardiologists report the successful reduction in the time between onset of chest pain and primary angioplasty when the ECG of patients is transmitted wirelessly from ambulance to the cardiologist's handheld PDA (Personal Digital Assistant). The clinician can make an immediate decision to redirect patients to the catheter lab saving time in transfers between hospital departments. Clemmensen P, Sejersten M, Sillesen M et al. Diversion of ST-elevation myocardial infarction patients for primary angioplasty based on wireless prehospital 12-lead electrocardiographic transmission directly to the cardiologist's handheld computer: a progress report. J Electrocardiol. 2005 Oct;38(4 Suppl):194-8


  • Acierno. The History of Cardiology. 1994. New York: Parthenon.
  • The Bakken Library and Museum
  • Bibliotheque Inter-Universitaire de Medicine, Paris. Source of the images of 'Descarte's reflex' from De Hominis and Swammerdam's possible electrical stimulation of a nerve-muscle preparation.
  • Burchell HB. A centennial note on Waller and the first human electrocardiogram. Am J Cardiol 1987;59:979-983
  • Burnett J. The origins of the electrocardiograph as a clinical instrument. Medical History Supplement 5: 1985, 53-76. Published as a monograph. The emergence of modern cardiology. Bynum WF, Lawrence C, Nutton V, eds. Wellcome Institute for the History of Medicine:1985.
  • Cobb, Matthew. Exorcizing the animal spirits: Jan Swammerdam on nerve function. Nature Reviews, Neuroscience 2002;3:395-400
  • On Animal electricity: Being an Abstract of the Discoveries of Emil Du Bios-Reymond (translated). Edited by Dr Bence Jones. 1852. Churchill: London.
  • Fye WB. A history of the origin, evolution, and impact of electrocardiography. Am J Cardiol 1994;73:937-949
  • Geddes LA. Supplement. The Physiologist 1984;27(1):S-1
  • Hewlett-Packard - 'History and Mission'
  • The Heart Rhythm Society - Timeline.
  • Berndt Luderitz. History of the Disorders of Cardiac Rhythm. Third Edition. 2002. Blackwell Publishing.
  • Jaakko Malmivuo & Robert Plonsey: Bioelectromagnetism - Principles and Applications of Bioelectric and Biomagnetic Fields, Oxford University Press, New York, 1995
  • Nobel Institute. Presentation speech by Professor JE Johansson. The Nobel Prize in Physiology or Medicine 1924.
  • North American Society of Pacing and Electrophysiology.
  • Pumphrey S. Latitude and the Magnetic Earth. Icon books, Cambridge: 2002. (see also the William Gilbert website)
  • Royal Humane Society, Annual Reports. Brettenham House, Lancaster Place, London, WC2 7EP.
  • Schamroth L. The 12 Lead Electrocardiogram. Blackwell Scientific Publications, Oxford: 1989.
  • Hurst JW. Current Perspective: Naming of the Waves in the ECG, With a Brief Account of Their Genesis. Circulation. 1998;98:1937-1942.
  • Snellen HA. Willem Einthoven (1860-1927) Father of electrocardiography. Kluwer Academic Publishers, Dordrecht: 1995. with thanks to Kees Swenne
  • Titomir LI. The remote past and near future of electrocardiography: Viewpoint of a biomedical engineer. Bratisl Lek Listy 2000;101(5):272-279.

Monday, 7 April 2014

Pharma blog: Drug for Psoriatic arthritis

Pharma blog: Drug for Psoriatic arthritis: The U.S. Food and Drug Administration approved Otezla (apremilast), manufactured for Celgene Corporation, Summit, N.J.,  to treat adults ...

Drug for Psoriatic arthritis

The U.S. Food and Drug Administration approved Otezla (apremilast), manufactured for Celgene Corporation, Summit, N.J.,  to treat adults with active psoriatic arthritis (PsA), which is a form of arthritis that affects some people with psoriasis. Most people develop psoriasis first and are later diagnosed with PsA. Joint pain, stiffness and swelling are the main signs and symptoms of PsA.

“Relief of pain and inflammation and improving physical function are important treatment goals for patients with active psoriatic arthritis,” said Curtis Rosebraugh, M.D., M.P.H., director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “Otezla provides a new treatment option for patients suffering from this disease.”
Currently approved treatments for PsA include corticosteroids, tumor necrosis factor (TNF) blockers, and an interleukin-12/interleukin-23 inhibitor.
The safety and effectiveness of Otezla, an inhibitor of phosphodieasterase-4, were evaluated in three clinical trials involving 1,493 patients with active PsA. Patients treated with Otezla showed improvement in signs and symptoms of PsA, including tender and swollen joints and physical function, compared to placebo. Treatment with Otezla was also associated with an increase in reports of depression compared to placebo.
The FDA is requiring a pregnancy exposure registry as a post-marketing requirement to assess the risks to pregnant women related to Otezla exposure.
In clinical trials, the most common side effects observed in patients treated with Otezla were diarrhea, nausea, and headache.

Friday, 4 April 2014


Researchers from the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, in collaboration with materials scientists, engineers and neurobiologists, have discovered a new mechanism for using light to activate drug-delivering nanoparticles and other targeted therapeutic substances inside the body.
This discovery represents a major innovation, said Adah Almutairi, PhD, associate professor and director of the joint UC San Diego-KACST Center of Excellence in Nanomedicine. Up to now, she said, only a handful of strategies using light-triggered release from nanoparticles have been reported.

The mechanism, described in the April 1, 2014 online issue of ACS Nano, employs near-infrared (NIR) light from a low-power laser to heat pockets of water trapped within non-photo-responsive polymeric nanoparticles infused with drugs. The water pockets absorb the light energy as heat, which softens the encapsulating polymer and allows the drug to be released into the surrounding tissue. The process can be repeated multiple times, with precise control of the amount and dispersal of the drug.

"A key advantage of this mechanism is that it should be compatible with almost any polymer, even those that are commercially available," said Mathieu Viger, a post-doctoral fellow in Almutairi's laboratory and co-lead author of the study. "We've observed trapping of water within particles composed of all the biodegradable polymers we've so far tested."

The method, noted Viger, could thus be easily adopted by many biological laboratories.

The combined use of hydrated polymers and near-infrared light appears to resolve a host of technological and health barriers that have hindered previous, similar approaches. Earlier efforts to use NIR-triggered release have not been widely exploited because they required special designer polymers, expensive high-powered lasers and/or the co-encapsulation of inorganic particles whose safety in the body remains questionable.

The new method described by Almutairi and colleagues in the departments of Mechanical and Aerospace Engineering, Neuroscience, and Chemistry and Biochemistry at UC San Diego uses NIR at a vibrational wavelength cued to excite water molecules, which absorb the optical energy and convert it to heat. NIR is capable of penetrating biological tissues to greater depths than visible or ultraviolet light.

Co-lead author Wangzhong Sheng, a graduate student in Department of Mechanical and Aerospace Engineering, explained the selectivity of heating by comparing the trapped water within particles to a glass of water and the surrounding water within the solution or tissue to a bathtub. The smaller amount of water is heated much more rapidly because of the enormous volume difference.

An obvious use of the method, said Almutairi, is light-triggered drug delivery, but with more research, she anticipates the new method could provide a variety of industrial, medical and scientific applications, including "any technological application requiring that chemistry be controlled in time and in space, such as in catalysis or self-repairing materials or light-activated sunscreens or pesticide dosing."

Co-authors include Carl-Johan Carling, Jacques Lux and Caroline de Gracia Lux, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences; Kim Dore and Roberto Malinow, UCSD Department of Neurosciences; Ali H. Alhasan, UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and UCSD Center of Excellence in Nanomedicine; and Madeleine Grossman, UCSD Department of Chemistry and Biochemistry.

Funding for this research came, in part, from a National Institutes of Health New Innovator Award (1 DP2 OD006499-01) and NIH grant R01AG032132. This research is in partnership with the King Abdulaziz City of Science and Technology.