In
regard to Einthoven's work, Professor J.E. Johansson, Chairman of the Nobel Committee
for Physiology or Medicine of the Royal Caroline Institute, made the following
statement*
In
regard to Einthoven's work, Professor J.E. Johansson, Chairman of the Nobel Committee
for Physiology or Medicine of the Royal Caroline Institute, made the following
statement*
The Staff of Professors of the Royal Caroline
Institute has on 23rd October, 1924, decided to confer this year's Nobel Prize
in Physiology or Medicine to the Professor of Physiology at the University of
Leiden, Willem Einthoven, for his discovery of the mechanism of the electrocardiogram.
Einthoven's name is linked partly with the design of a physical instrument,
the string galvanometer, partly with the so-called electrocardiogram,
a record of the electrical potential fluctuations at the surface of the body,
which accompany the heart beat. The heart beat, like the piston movement of a
steam engine, is a cyclic process. Behind this process lies, in the first place,
a similarly cyclic process in the heart muscle.
For the present this
process is called the «muscular process», in analogy with «neural
process» and «glandular process». All these processes, which
with regard to energy must be considered as a conversion of chemical energy into
forms of energy other than heat, are accompanied by a fluctuation in the electrical
potential - the action current - which as a rule is extremely weak and which does
not play any role in the life of the individual, but which from the viewpoint
of experimental technique, however, is of the greatest interest, in so far as
it allows the registration of the frequency of the functional process and its
propagation through the individual organs.
The potential fluctuations
concerned are measured in millivolts and in hundredths of seconds. To construct
a self-registering measuring instrument which records directly and truly the potential
variations of this order of magnitude was a problem which Einthoven has solved
with his string galvanometer (1903). In constructing this, he started from
the well-known Deprez-d'Arsonval «moving-coil galvanometer» and had
herein replaced the moving parts - coil and mirror - with a fine, silver-plated
quartz wire, which was stretched in the field between the poles of the magnet
and at the same time between an optical illumination system, and another one for
projection. The reduction in mass of the moving parts, achieved in this way, allows
at the same time high sensitivity and short adjustment time.
After
testing the practicability of the instrument for various purposes, and after a
thorough analysis (1906) of the dependence of the string galvanometer curve on
the mass and tension of the string, and on the damping of the deflection, the
latter by electromagnetic means and by the effect of the air resistance, Einthoven
published in 1909 the first detailed description of the instrument. Interest in
the string galvanometer spread very rapidly, and string galvanometers of various
types after Einthoven's specifications were supplied by several famous instrument
firms.
Using strings of ultramicroscopic size in a vacuum between
the poles of a magnet, Einthoven recently succeeded in registering potential fluctuations
of a frequency far beyond the limits of known physiological phenomena. In this
connection it may also be mentioned that he has registered sound waves with a
frequency of more than 10,000 vibrations per second, by means of strings of the
dimensions previously mentioned in association with suitable optical systems.
The construction of the string galvanometer was a purely physical problem.
The interest shown by physiologists and physicians in this achievement, is caused,
as already mentioned, by the possibilities of analysing, by means of the registration
of the so-called action currents, some phenomena in the living organism. The string
galvanometer has therefore been widely used for various purposes in physiology.
To give an idea of this, some phenomena may be mentioned, which by means of the
string galvanometer have been investigated by Einthoven himself: the retina current
(1908, 1909), the action currents in nervus vagus (1908, 1909) and in the sympathetic
chain (1923), the psychogalvanic reflex (1921), the Gaskell effect (1916), the
muscular tone (1918). With regard to the action current of the muscle Einthoven
demonstrated (1921) in a convincing manner that this occurs exclusively as a phenomenon
accompanying the mechanical effect known for a long time - a fact very important
to the concept of the action current.
The achievement for which the
Staff of Professors of the Royal Caroline Institute awarded Einthoven the Nobel
Prize, is in the field of the heart physiology. Einthoven's interest in the action
current of the heart dated from 1891; at that time, as a result of the investigations
of Burdon-Sanderson (1879) and Augustus Waller (1887, 1889) attention was focussed
on this phenomenon.
Both scientists used the well-known Lippmann
capillary electrometer, which registers potential variations; but the adjustment
time is rather long, and the capillary electrometer curve, therefore, does not
reflect in a direct manner the actual time process of the potential changes in
the heart muscle during heart beat. Einthoven developed a rather simple method
of correction (1894) and could with this derive the actual electrocardiogram
from the capillary electrometer curve (1895). The details herein he denoted as
P, Q, R, S, T: terms which are preserved to this day. This method, however, would
never have any practical significance in reproducing the electrocardiogram of
man. It is much too laborious for this. Einthoven saw the importance of an instrument
which directly renders the potential variations with time during these
processes, and the result was the string galvanometer described above (1903).
The curve recorded by this instrument during the registration of the action current
of the heart showed perfect agreement with the electrocardiogram derived from
the capillary electrometer curve, and this agreement between the results of the
two registration methods, fundamentally so different from one another, proved
beyond all doubt that the actual time process of the potential variation accompanying
the heart beat had been obtained. Einthoven can thus with full justification
be named the discoverer of the real electrocardiogram.
One of
the first results of this discovery was the demonstration that each individual
has his own characteristic electrocardiogram, but that the electrocardiogram
of all individuals in the main conform to a general type. In a publication «Le
télécardiogramme» (1906) Einthoven returns to the same subject,
revealing, however, at the same time a fact which has acquired the greatest clinical
significance: that different forms of heart disease reveal themselves characteristically
in the electrocardiogram. He gives examples of the electrocardiograms of patients
with hypertrophia of the right ventricle during mitral insufficiency, hypertrophia
of the left ventricle during aorta insufficiency, hypertrophia of the left auricle
during mitral stenosis, of patients with degeneration of the heart muscle, also
of electrocardiograms during various degrees of heart block, during extrasystoles,
true «atypical heart systoles» of two different types, as well as
during what is now called «ataxia cordis». In a subsequent work «Weiteres
über das Elektrokardiogramm» (More about the electrocardiogram) in
1908, he communicates other cases. Einthoven's interest for the electrocardiogram
from clinical point of view is also evident from a proposal, put forward by himself
(1906), namely, to establish so-called telecardiograms, i.e. to have electrocardiograms
produced by a string galvanometer in a physiological laboratory from patients
lying in a hospital several kilometers away. Nowadays, since a string galvanometer
is available in almost any large hospital, this detail is only of historical importance.
It can be said that this new method of investigation fulfilled a need
in clinical medicine. One needs only to remember the curves of venous and
arterial pulses, and cardiograms at disposal up till then - all of them difficult
to interpret - whenever a case of arrhythmia had to be cleared up. Moreover, some
«stroke of luck» was indispensable, even if one is a well-trained
experimentator, to obtain a «mechanical» cardiogram from a person,
which entirely corresponds with one taken some hours before. The string galvanometer,
on the other hand, once set up and adjusted, operates ideally, «accident»-free.
What did the electrocardiogram mean at that time? Einthoven said in his
work in 1895 that the efforts to fully interpret the electrocardiogram should
be abandoned for the moment, and in a survey of the relevant literature up to
the first half of 1912, the author** put emphasis on the uncertainty of the efforts
to interpret the cardiogram. It can therefore be said that Einthoven had in 1895
discovered some sort of writing the contents of which for many years after remained
in virtual obscurity.
However, in his work in 1908 Einthoven gave
an interpretation of the electrocardiogram. He starts from the fact that
the stimulus (of the contraction process, the «negativity») is propagated
as a wave in the muscular system of the heart. The string of the galvanometer,
connected with the heart in a closed circuit in one of the usual ways, remains
in the original position not only when the heart is at rest, but also when the
«negativity» of the assemblage of points of the heart wall show the
same value. A deflection is therefore in the first place to be expected at the
beginning and at the end of a systole, and it presupposes that the condition of
activity does not occur, respectively cease, simultaneously in all elements of
the muscle. Further: if the contraction process (the stimulus) is propagated symmetrically
in relation to the points connected to the galvanometer, then no deflection would
take place either. Under such circumstances the electrocardiogram must be determined
partly by the starting-point of the stimulus to the heart beat, partly by the
conduction system within the heart. The point of departure for the normal heart
beat has been sufficiently well known since the middle of the 1890's, the bundle
of His also since that time, and Tawara's description of the ramification of the
conduction system inside the ventricles known since 1906. According to Einthoven
the P-peak is an expression of the propagation of the stimulus wave in the muscular
system of the auricle. The negativity wave, corresponding to the stimulus wave
in the His-Tawara system, is considered too weak by Einthoven to cause any deflection
in the galvanometer. The QRS-complex is determined by the propagation of the stimulus
wave in the muscular system of the two ventricles, proceeding in unsymmetrical
fashion to the points of lead, starting at different moments at the transition
of the tree-like ramified Purkinje's fibres into the various parts of the proper
muscular system of the heart. When the contraction process has reached its maximum
in all the points of the ventricular wall, the string returns to its original
position. When the contraction ceases in the various parts at different moments,
a T-peak is obtained.
It is unnecessary in this connection to consider
the interpretations proposed by other investigators, as Einthoven's concept
is the only one which has proved to be tenable. The interpretation that the
P-peak belongs to the auricular systole is mainly based on his observation of
electrocardiograms in cases of heart block in patients or during vagus stimulation
in dogs. With regard to the interpretation of the QRS-complex Einthoven was evidently
the first who has clearly recognized the significance of the conduction system
in this connection. The train of thought in the interpretation of the T-peak can
already be detected in Burdon-Sanderson's previously mentioned work.
Already Waller (1887) had observed that the deflections of the capillary electrometer
vary accordingly as the lead is taken from both hands or from one hand and one
foot, etc., and based hereupon his well-known scheme of the potential distribution
in the body in relation with the heart's action current - a scheme later adopted
in textbooks and handbooks. The scheme has principally been used to demonstrate
that the amount of deflection, i.e. the «peaks» in the electrocardiogram,
must vary in accordance with the manner in which the electrodes have been applied
in relation to the heart axis. Einthoven pointed out, however, that not only the
amount of the deflection but also the shape of the entire electrocardiogram
is changed when one manner of leading is replaced by another (1908). One of
the spikes may be accentuated while another may be suppressed, etc. One and the
same spike resulting from different leads does not always correspond with the
same phase of the heart period. Einthoven therefore found it essential to always
indicate the manner of leading, and in connection with this he proposed (1908)
the now generally accepted standardization: Lead I, II, and III.
In a publication (1913) Einthoven has shown how the direction and definite
amount of the resulting potential difference at corresponding moments can
be calculated from the simultaneous deflections at the three leads indicated.
The direction of the resulting potential variation corresponds in a certain way
to the electrical axis in Waller's scheme, and several authors use the term «electric
axis» instead of Einthoven's designation. Waller made this axis to coincide
with the anatomical axis of the heart, an obvious procedure, since at that time
it was generally believed that the heart - as to the propagation of the stimulus
wave - could be identified with a muscle with fibres running parallel, stimulated
at one end. In fact, the resultant potential variation (the «electric axis»),
as shown by Einthoven, changes its direction from one moment to the other during
the heart period. The rotation of the electric axis during the heart period is
nothing else than an expression of the course of the stimulus wave through the
heart muscle, as is evident from the electrocardiogram at the three leads indicated.
Already in his papers in 1906 and 1909 Einthoven pointed out on the basis of the
shape of the electrocardiogram that the starting-point for the so-called atypical
ventricular systoles must be other than for the normal, and showed that a combination
of electrocardiograms at different leads supplies a possibility of deciding where
this starting-point is located. The calculation of this direction of the resultant
potential variation is a refinement of this method which can be used when an evaluation
of the electrocardiogram by visual inspection is not sufficient.
Such a calculation is very simple. The difficulty consists in establishing the
corresponding phases in the combination of electrocardiograms at the three leads.
Hereby, as pointed out by Einthoven, we can make use of the electrophonocardiogram.
However, the safest way is to register simultaneously the electrocardiogram
at the three leads, or at least at two of them. Einthoven has given a particularly
elegant design for such an instrument (1915, 1916) - two galvanometers one after
the other, each transferring its string registration on the same plate. The firm
of Carl Zeiss has carried out such a detailed construction.
Thus
Einthoven has added the discovery of the mechanism of the electrocardiogram
to the discovery of the true, individual electrocardiogram. Sir Thomas Lewis was
the first who realized the importance of Einthoven's discovery and who followed
his line of thought. His elegant demonstration (1916) of the QRS-complex in the
electrocardiogram by means of an algebraic summation of dextro- and laevogram
confirmed the correctness of Einthoven's interpretation, just as his demonstration
of the «circus movements» of the stimulation wave (1921) in cases
of auricular fibrillation proved conclusively the practical importance of Einthoven's
calculation of the «direction and definite magnitude of the resultant potential
variation». The examination of literature in this field fully justifies
the statement that the importance of Einthoven's discovery of the mechanism of
the electrocardiogram has only been conclusively proved by Sir Thomas Lewis's
works previously mentioned.
Since Einthoven first described the details
of the electrocardiogram and more so after the publication in 1906 of its appearance
during the various heart diseases, a vast literature in this field has accumulated
over the years. All these researches aim fundamentally to reveal the mechanism
which underlies the electrocardiogram. The question then arises: Which facets
of this mechanism have been brought to light? Let us imagine that a heart model
made from fresh heart muscles is placed in a homogeneously conducting medium with
leads connected with a string galvanometer, and let us ask ourselves the question:
What should be put into this model so that it will give the customary electrocardiogram?
The answer now would be: (1) the conduction system; (2) a conduction velocity
in this system which is several times greater than that in the heart muscle. Einthoven
was the first to point out the importance of the conduction system. The importance
of the conduction velocity has been shown by Lewis.
The same mechanism
governing the characteristics of the electrocardiogram, also governs the characteristics
of the mechanical process during the heart beat. We should remember in this connection
that the mechanical process not only consists of the succession of the stimulation
of the separate parts of the heart compartments, but also of the cooperation of
the individual parts of the heart wall which form the essential condition for
the mechanical effect in the individual ventricle or in the individual auricle.
A deficiency in this cooperation can, with regard to the mechanical effect, be
as fatal as a valvular insufficiency. Today, the importance of the mechanism discovered
by Einthoven can easily be realized.
*
Professor Einthoven being on a lecture tour in the United states, and the other
laureate of the year also being unable to come to Stockholm, the usual ceremony
on December 10 was cancelled.
** P.H. Kahn, «Das Elektrokardiogramm»,
Ergeb. Physiol., 14 (1914) 1.
From Nobel Lectures, Physiology or Medicine 1922-1941, Elsevier Publishing Company, Amsterdam, 1965
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