Nobel Lecture, December 11, 1956
The ancient world and the Middle Ages had no idea of the existence of the circulation of the blood. It was not until the Late Renaissance that efforts were made to grasp this process anatomically and understand its function. Thus, Miguel Serveto searched in vain for a connection between the right heart and the left, and in so doing discovered the lesser circulation in 1553. In 1569, Caesalpinus traced the path of the large circulation. Jacobus Sylvius (1543), Canani (1564), and Fabricius of Aquapendente (1574) concurred in recognizing the centripetal movement of the venous bloodstream from the structure and arrangement of valves in the veins. Before their time it had been believed that blood flowed outwards to the periphery, even in the veins.
William Harvey, one of the most gifted pupils of Fabricius (1578-1657), combined all these individual findings with the results of his own research to form the general picture of what we today call the circulation of the blood. But even he had no clear idea of the circulation in the region of the capillaries. This section was explained and described for the first time by Malpighi in 1661, after he had viewed a frog's lung under a microscope.
In any event, it is the year 1628, in which Harvey published his classic work De motu cordis et sangunis, that we can call the birth-year of cardiology.
However, this great discovery appears to have had no immediate effect on the method of observing the function of the sound and sick heart. This had to wait some 170 years, until, at the end of the eighteenth and the beginning of the nineteenth centuries, scientific methods of examination made their appearance in medicine. The beginning of this epoch was marked by the introduction of digitalis for the treatment of oedema, achieved by William Withering in 1785.
Further milestones on the way were the introduction of percussion by Auenbrugger in 1761 and of auscultation, by Laëmec. These innovations made the increasingly refined discoveries of the new science of pathology useful at the sickbed. The last landmark of this period was Einthoven's introduction of the electrocardiogram into clinical practice and research rays, discovered shortly before, enabled the grosser modifications of the heart's structure to be seen even in a living person.
With this, cardiology had entered a stage of stagnation, which made it necessary to seek new and more exact methods than those hitherto available.
The starting-point of the modern trend in research came from classic French experimental physiology, notably the trials on animals to obtain blood for metabolism experiments described by Claude Bernard in his Physiologie opérative. In particular, the procedure employed by Chauveau and Marey in 1861 became the model. They were the first to achieve measurement of blood pressure inside the heart and the recording of pressure curves from the interior of the heart of a living animal. This was done with manometers, which were led from the neck vessels into both compartments of the right heart as well as into the left heart chamber.
But even Claude Bernard, Chauveau, and Marey had been forestalled. As far as I know, the credit for carrying out the first catheterization of the heart of a living animal for a definite experimental purpose is due to an English parson, the Reverend Stephen Hales. This scientifically interested layman undertook in Tordington in 1710, 53 years after the death of William Harvey (1578-1657), the first precise definition of the capacity of a heart. He bled a sheep to death and then led a gun-barrel from the neck vessels into the still-beating heart. Through this, he filled the hollow chambers with molten wax and then measured from the resultant cast the volume of the heart-beat and the minute-volume of the heart, which he calculated from the pulse-beat. Besides this, Stephen Hales was also the first, in 1727, to determine arterial blood pressure, when he measured the rise in a column of blood in a glass tube bound into an artery.
In 1912, Unger, Bleichröder, and Loeb published a work under the title Intra-arterial therapy. They were at that time aiming at a special chemotherapy for puerperal sepsis. In order to bring a drug in the greatest possible concentration to the place where it was needed, they wanted to insert ureter catheters into human patients from the leg arteries up to the presumed height of the fork of the aorta and inject from there. After experiments on animals, they carried out vein probings on four people as a preliminary trial from the point of view of intra-arterial therapy. These caused no ill effects. No X-ray checks were used, nor were the cardiological aspects taken into consideration.
In 1928, the Italian Montanari carried out probing of the right heart on animals and on the human cadaver.
Here I may as well review my own first attempts at probing the right heart, undertaken in 1929 and based on the work of Chauveau and Marey.
The reason they at first made no headway was because, in the years 1929-1931, all the technical requirements for the planned investigations were lacking and had first to be laboriously created. So it can be understood that it was some time before the broad outlines of important problems of developing modern cardiology could be seen emerging from my admittedly rather unusual experimental procedure. Perhaps it is significant that the pioneer work of O. Frank and Broemser on the development of the manometer also took place in these years.
Thus the experimental methods and the results they yielded needed many years to come to fruition. They achieved their modern practical significance only because fundamental discoveries had been made in other fields, for example in modern anaesthetic techniques, in antibiotics and through the pioneering publications of Helen Taussig, which in time bore further fruit. Nevertheless, in 1930, about six months after my first publication, O. Klein reported from Nonnrenbruch's Prague clinic on a series of patients whose heart minute-volumes he had ascertained according to Fick's principle, by means of the heart catheter. This procedure has its place even today in the standard practice of heart and lung clinics.
At the same time; I carried out my first experiments in angiocardiography. Here for the first time the living heart of a dog was successfully visualized radiologically with the aid of a contrast medium. Even at that time, the complete lesser circulation in the dog could be shown with the cinematographic radioscopy according to Gottheiner.
Although no results could be attempted with human beings, because no apparatus had been devised, their possibility had at least been demonstrated in principle. Only four months after this publication, Moniz, Carvalho, and Lima were able to disclose rather better results. with them began the immense quantity of writing on angiocardiography.
Further development of technique was impeded not only by the absence of technical essentials and consequent lack of knowledge. To some outsiders, ethical considerations also weighed heavily in the balance against it. And when one thinks how hard men like Cournand and McMichael had to fight against such people in 1941 and later, one can perhaps understand what difficulties stood in my way twelve years before.
A turning-point in the history of cardiology is the year 1941, when Cournand and Ranges made known their first experiments with the heart catheter as a clinical method of investigation. But he will be reporting on this himself.
The work of Cournand and Richards and their pupils had fanned a small flame into a blazing fire which began to rage all over the world. The Cournand-Richards school achieved particularly fruitful results in the United States and Scandinavia. In England, McMichael is the most important advocate of this method of investigation. His great service is his employment of it to solve pharmacological problems.
For Cournand and McMichael, too, as they have told me themselves, the beginning was not easy. They, too, had strong resistance to overcome, the harder to deal with because people did not hesitate to obstruct practical research work with threadbare ethical and moral objections, such as are still occasionally raised today. But these voices also must fall silent now it has been shown, how responsibly this circulation research has been conducted everywhere and with what high moral earnestness it has been applied. And so now there is an army of diligent men and women at work, an army so big that it is impossible in this context to mention any beyond those named. You must pardon this omission.
As for angiocardiography, this method has given strong new impetus not only to cardiology, but also to X-ray technology as a whole. Whereas earlier X-ray diagnosis stopped short at explaining the morphology from the reproduction of shadows, here a leap was made right to the core of the function.
At this point, the close and inseparable interrelation of heart and lungs became obvious - something we had certainly guessed at, but which previously we could not grasp. And so, with the selective angiography of the lung vessels (Bolt, 1949-1950), our knowledge was consciously extended to the outermost periphery.
With this, heart catheterization had burst the bounds of cardiology in the stricter sense, and now set about conquering other fields of research.
Right at the start of my experiments upon animals it had occurred to me, as to other investigators, that one could penetrate diagonally through the right auricle from the upper into the lower vena cava. Now use is made of this path to collect blood from the liver, and it is to be hoped that many long-standing questions of metabolism will be solved in this way. The kidney, too, is accessible in the same manner. Thus it can be seen that heart catheterization must in no way be looked upon as an almost worked-out field of research.
Angiocardiography, in the form in which it is practised today, is of course still burdened with risks which impose limitations on its use. Its use cannot therefore be justified for examinations which are not strictly necessary, but here, too, new possibilities can be discerned.
Further development will in many cases enable us to dispense with the massive and dangerous quantities of contrast media which at the moment we still need, and to manage instead with smaller, less harmful amounts of radioactive isotopes. Their progress through the small circulation can already be followed in outline with Gripping's isotope retina, and shown graphically.
From all this, we can see that modern cardiology has become something much more universal than was originally supposed.
One may compare the art of healing with a work of art, which from different standpoints and under different lighting reveals ever new and surprising beauty.
So, besides the epochs of cellular and humoral pathology and many others, we can now perhaps speak of an age of cardiological and circulatory investigation. We do this with the comforting awareness that, by the correct application of their teaching, earlier discoveries remain useful to us, for they now appear in a new light. Thus we guard ourselves against the mistake which runs all through the history of medicine: that of concentrating dogmatically upon first one, then another facet of research, instead of standing back to view the whole as a growing entity.
From Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964
Copyright © The Nobel Foundation 1956
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