P&S Medical Review: August 1996, Vol.3, No.2
Cournand, Richards, and the Introduction of Cardiac Catheterization (Commentary by Dr. Yale Enson)

The reprinting of this paper commemorates the 40th Anniversary of Cournand and Richards' 1956 Nobel Prize in Physiology or Medicine in a most appropriate way since it marks the origin of the road that led directly to the award. Richards was educated at Yale, trained in Physiology and Medicine at Columbia University (M.A. '22, M.D. '23) and, subsequent to his house staff training at The Presbyterian Hospital, took a post-doctoral fellowship in London under Sir Henry Dale. He returned to Columbia as a junior faculty member in 1928. Cournand , following an education based on private tutoring, entered the Faculty of Science and then transferred to the Faculty of Medicine at the University of Paris in 1914, and resumed his medical education at the end of World War I. He received his clinical training at the Hospital Necker during the 1920's while participating actively, at the same time, in the rich cultural life of Paris during that period. At the end of the decade, Cournand sought further training in pulmonary medicine under James Alexander Miller, Director of the renowned Columbia Chest Service at Bellevue Hospital. During his residency, Miller suggested that Cournand participate in some of Richards' studies and he leapt at the opportunity.

At the start of their collaboration, Richards and Cournand were ideally situated: in an environment rich in clinical material and diagnostic acumen; and in a field lacking in both methodology and verifiable hypotheses to describe and explain the functional disturbances caused by lung diseases. Initially, Cournand had to be brought up to speed in a fashion best described in his own words: "... he introduced me to all the techniques he had mastered in his early investigations and to sound and precise physiologic method and thinking. To the demanding task master, to the scientific investigator, I owe more than I can tell." It is difficult to determine the duration of this apprenticeship, although one can imagine it lasted several years and did not end abruptly.

Richards had been heavily influenced in his thinking by the celebrated Harvard physiologist Lawrence J. Henderson and took as the point of departure of his own studies Henderson's precept that the lung, heart and circulation constituted a single system whose function was to extract oxygen from the atmosphere and transport it to the various tissues to support their activities. It was clear to him, early on, that the key evaluation that would permit a precise definition of this functional unit was an accurate measurement of pulmonary blood flow. The classical technique available for this assessment at the time was the "indirect Fick technique". The direct Fick technique, from which it evolved was developed during the 19th century for studies in animals. This benchmark method involved measuring oxygen consumption and mixed venous and arterial blood oxygen content so that blood flow could be calculated as follows:

pulmonary blood flow = O2 consumption/arterio-mixed venous O2 difference

Mixed venous blood was not available in man (thought to be too dangerous to obtain) so that a modification that substituted carbon dioxide for oxygen in the above equation was utilized. This indirect method did not sample mixed venous blood. Rather, it assumed equilibration between carbon dioxide in the alveolar air and mixed venous blood and involved measuring carbon dioxide in a re-breathing bag system where its concentration in the bag was assumed to reach equilibrium with mixed venous blood. Arterial carbon dioxide content was obtained from samples obtained by direct arterial puncture.

Cournand and Richards' first efforts were devoted to measurement of lung volumes in normal individuals and in patients with various forms of chronic, diffuse lung disease. New methodologies were evolved and the first descriptions of the maldistribution of respiratory gas by airway obstruction were reported. Within five years these methodologies had become sufficiently sophisticated as to permit the evaluation of mechanical respirators developed by the army air force, first in normal individuals and then in patients with respiratory failure. Unfortunately the "indirect Fick technique" proved to be inadequate for measuring pulmonary blood flow during this period, especially in patients with chronic lung disease: on the one hand, uniform equilibration between carbon dioxide in mixed venous blood and in alveolar air did not exit; on the other hand, even in normal subjects, small shifts in the level of ventilation destroyed the "steady state" conditions necessary for successful measurements.

By 1936 it was clear to both workers that it would be necessary to sample mixed venous blood directly to measure pulmonary blood flow. They were aware of Forssmann's report of catheterization of his own heart in 1929, and of subsequent pioneering work by European radiologists who injected contrast material into the right atrium for diagnostic purposes. Cournand embarked on a demonstration of the feasibility and safety of catheterizing the right heart, first in dogs, then in a chimpanzee, and finally in man, since others had discredited such attempts because of presumed dangers. A number of features of their first major paper, reprinted herein, merit comment. The introduction indicates that safety, the prime consideration had been demonstrated previously in 30 initial subjects. This conclusion is corroborated in the present report in 14 individuals, 5 of whom had serious heart disease. Sampling mixed venous blood and measuring pulmonary blood flow was demonstrated as being feasible. The inclusion of normal subjects and those with heart disease permitted an initial description of the hemodynamic abnormalities encountered in heart disease, demonstrating the diagnostic value of the technique. Consideration of the location of the tip of the catheter is presented in detail because of the importance of setting an arbitrary zero level of pressure in the normally low pressure right heart and pulmonary circulation. Five cm below the angle of Louis, as suggested in this report, remains the widely accepted zero point at this Medical Center and most others around the world to the present day. In addition to safety, painlessness, feasibility and diagnostic value this paper illustrates one other virtue: that of academic strategy. Where else to present an important new technique but at the major meeting of academic medical scientists in this country?

Other aspects of this paper warrant mention: the catheters employed were ureteral catheters used by urologic surgeons; pressure levels were measured with water manometers with a low frequency response that afforded only mean pressures; and, finally, the value of men's three-piece suits. All blood samples were tucked into vest pockets (to maintain them at body temperature) and carried from Bellevue up to the Medical Center for analysis.

World War II interfered, for a time, with further development and wider application of this technique. Under the auspices of the Office of Scientific Research and Development, studies of the physiologic disturbances encountered in various forms of shock were undertaken by the Bellevue group under the leadership of Richards and Cournand. A description of the catheterization room at Bellevue Hospital during the mid-1940's may be of interest. The early fluoroscopes, used to guide passage of the catheter, did not couple the x-ray tube to the luminescent screen. Imagine one post-doctoral fellow manipulating the screen to follow the catheter tip while his wife (also a fellow) lay on the floor below the fluoroscopy table moving the x-ray tube to follow the screen. Once the catheter was in place all lights were turned off and the Hamilton manometer (an improvement over the original water manometer that focused a light on sensitive paper to permit recording of an undamped pressure contour) was manipulated in absolute darkness so that its light output could be captured with a hand-held mirror and adjusted to strike the paper. Not an easy procedure. All feared that attempts to catheterize the pulmonary artery might be excessively dangerous. Hence catheterization of that vessel was fortuitous. The momentum of flowing blood tends to carry catheters along in its direction (this phenomenon is responsible for development of the Swan-Ganz catheter). On several occasions in 1944 Cournand noted that the right atrial catheter suddenly appeared in the pulmonary artery at a time when no manipulations were being made. The catheters were permitted to remain in this position for prolonged periods without side effects or complications. As a consequence catheterization of this vessel became a routine feature of hemodynamic evaluations.

The conclusion of the war permitted an explosion of activity: in short order the electronic advances achieved during the war were applied to pressure transducers and carrier amplifiers that permitted continuous intravascular pressure contour recordings; cardiac catheters fabricated from extruded nylon were designed to Cournand's specifications. The technology of modern cardiac catheterization laboratories had been developed and important new industrial activity generated. Within 5 years of the end of the war systematic descriptions were published of the hemodynamic abnormalities encountered in congenital heart disease; in pulmonary heart disease; and of the hemodynamic response in patients with heart failure to the administration of digoxin. In short order these were followed by detailed reports on rheumatic valvular disease, on pericardial restrictive disease, and on criteria for selection of candidates for cardiac surgery. Modern diagnostic cardiology had been established and the way paved for the development of interventive cardiology and radiology. These developments and publications brought a host of fellowship applicants to Cournand from the late 1940's on. Individuals were selected from a wide geographic range of centers in this country, Canada and western Europe. As these physicians left Bellevue they assumed leadership positions in cardiologic and pulmonary centers across this country and Europe, disseminating the concepts developed by Cournand and Richards and contributing to the primacy of their group.

It should be apparent from the foregoing that innovation (which permitted quantification of hemodynamic events) produced a paradigmatic shift in cardiologic diagnosis; that the importance was widely recognized and had a profound impact on patient management, on medical education, and on the bio-medical industry; and that general acceptance was facilitated by a broad geographic dissemination of Richards and Cournand's trainees. Each of these factors played a role in the ultimate decision to honor them with the Nobel Prize.