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.
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