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Biographical Memoirs ANDRÉ FRÉDÉRIC COURNAND September 24, 1895–February 19, 1988 BY EWALD R. WEIBEL THE SUBTITLE OF André Cournand's autobiography—The Intellectual Adventures of a Medical Scientist—conveys the essence of his life. As a basic scientist he was a medical man concerned about helping his patients through fundamental research. As a medical scientist he was adventurous, just as he had dared to climb high mountains in his younger years. His courage to introduce a catheter into a man's heart changed physiology, but only because of its intellectual backing by a rigorous analytical concept. André Cournand was an artist among scientists; he combined imagination with discipline and rigor in his analytical approach, a sense of drama with critical thinking about the course to take both in his research projects and, in later years, in his concerns about shaping the future. André Frédéric Cournand was born in Paris, where he lived the first thirty-five years of his long life until his emigration to the United States. He felt very much French and European. His mother was the daughter of an Alsatian businessman, and his father descended from a Corsican author and poet who had participated in the French revolution of 1848. As Cournand writes in his autobiography, the influence of his mother was to give him a strong sense for the

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Biographical Memoirs arts and an inclination toward adventure: “In my mother the adventurous spirit expressed itself primarily through imagination and sympathetic recognition of the impetus of adventure in others. This same eager readiness for the new and the unexpected was to make its influence felt in my own life.” He was to receive a classical education, but at the age of sixteen he left the lycée to split his time between private tutoring in philosophy and work in a private laboratory to learn about scientific techniques. He nevertheless completed his undergraduate studies and enrolled in the Faculty of Sciences in order to be admitted to the Faculty of Medicine, a decision prompted chiefly by the influence of his father. Cournand's father, Jules, was a dentist in private practice but of high renown academically, particularly because of his many innovations in dental technology for which he was awarded twenty-five patents. “My father inspired my interest in medicine and helped me to conceive it as neither an academic discipline nor a field of practical action alone; rather, he showed me by example how the interaction of theoretical and clinical interests could provide the basis for imaginative creations that contributed both to general knowledge and to solution of practical problems,” writes Cournand, and this should, indeed, become the hallmark of his career in medical science. With his father he would not only explore the treasures of Paris but also begin his long career in mountain climbing. In 1914 Cournand entered the Faculté de Médecine, just as World War I broke out. Even before his first year of medical school ended, he was enlisted in the army to serve as auxiliary battalion surgeon, for the most part in the trenches near the German enemy. For his distinguished services tending wounded soldiers at the front he was awarded the Croix de Guerre with three bronze stars. This experi-

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Biographical Memoirs ence in the battlefield lasted three and one-half years and left a deep impression on him: “It had been necessary to develop the attitudes of mind and feeling to face danger and take risks,” and he believed that this was the undergirding of his emerging dual disposition to be open to the intellectually new and skeptical of received wisdom. After returning from the war and recovering from some injury incurred at the end of his service, Cournand resumed his medical studies in 1919. During his internship he trained in pediatrics, chest diseases, internal medicine, and neurology in the Hôpitaux de Paris. He prepared his dissertation, required for the M.D. degree, on the topic of acute disseminated sclerosis (“La Sclérose en plaques aigue”), which involved experimental studies at the Institut Pasteur on isolating a virus from brain tissue. In his autobiography Cournand remains rather brief on his career as an intern in Paris, but he notes that his promotions came with difficulty. For one, his “conception of liberal thinking and action” did not help him in the still conservative French medical system marked by paternalism, but then also he spent much of his time and energy on a different type of activity. During his service at the front he became friends with the young painter Jean Lurçat, who later became the famous designer of tapestries. This friendship brought Cournand into close contact with the so-called modern movement that determined the art life in Paris during the 1920s; he was introduced into the circle around Jeanne Bucher, whose gallery was an important meeting point for the modern artists. Here he met, among many other artists of renown, Jacques Lipschitz, one of the leading sculptors of the cubist period, with whom he maintained a lifelong close friendship. It was in this circle that he met his future wife, Sibylle, the younger daughter of Jeanne Bucher and her husband, the Swiss pianist Fritz Blumer. They married

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Biographical Memoirs several years later and raised four children: three daughters, Muriel, Marie-Eve, and Claire, and Sibylle's son by a first marriage, Pierre Birel Rosset. Around 1930 Cournand felt ready to go into private medical practice. But since he wanted to specialize in chest diseases he decided to enlarge his experience by working for one year in an American hospital. He felt fortunate to be admitted as resident to the well-known Chest Service at Bellevue Hospital in New York City. After a few months of service, partly in a sanatorium, Cournand was offered the possibility to participate in a long-range research project on pulmonary physiology by joining the group of Dickinson Woodruff Richards, a man of his own age but already quite advanced as an investigator. To accept this offer, however, meant not to return to France. Considering Cournand's exquisitely “French” or even “Parisian” life-style during the past decade this required a radical decision, but one taken by him and his wife with a positive mind. In his autobiography Cournand justifies this decision with several arguments. One was that the “free exchange of views in the United States had made a strong impression” on him and that here he would have “the prospect of an academic career where achievements count far more than nepotism.” And he says that, in retrospect, the possibility to “leave behind a way of life whose disregard for the conventional bore little relationship to some values that constituted the treasure of my education” was an additional though unconscious element. Last, but not least, he felt excited “to participate in creating techniques to be applied to new protocols of clinical investigation and in rationalizing treatment.” He returned to Paris briefly in 1932 to arrange his affairs after the accidental death of his father and then came back to New York to stay. But he always remained much attached to his home country. A large artistic map of Paris adorned one wall in

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Biographical Memoirs his office at Bellevue, and he used to remark: “Je n'aime pas les départs . . . sauf pour Paris.” THE SHAPING OF AN INVESTIGATOR Cournand's serious research activity began with what he called his “transplantation to the United States.” In his bibliography he lists ten papers from his time in Paris, mostly case reports presented to French medical societies. When, in 1933, he published his first major paper he was already thirty-eight years old. It was a report on his work at the Bellevue Hospital Chest Service but was written in the European tradition, based purely on clinical evidence (1933,1); it makes no reference to pulmonary function tests that would be the main focus of Cournand's subsequent work, which, indeed, was already ongoing at the time of publication (1933,2). Cournand became an experimental investigator through his association with Richards, with whom he remained closely associated throughout their lives and with whom he won the Nobel Prize in 1956.1 Born in New Jersey the same year as Cournand, Richards also took up his medical studies in 1919 after some war service. Already during his residency he began with research projects that he extended during a fellowship in Sir Henry Dale's laboratory in London. Back in New York he directed his research to blood and circulation. One aspect of these studies was to improve on blood gas measurements, particularly of CO2, because this was needed for the estimation of cardiac output. The so-called indirect Fick method then in use calculated cardiac output (or total blood flow) as the ratio of CO2 output from the lung to the CO2 concentration difference between the blood entering and leaving the lung. Whereas CO2 concentration in arterial blood was easy to measure, CO2 concentration in

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Biographical Memoirs mixed venous blood had to be estimated indirectly from the CO2 partial pressure in alveolar air. When Cournand joined Richards in 1932 he became involved with this line of work. His first project was to test and improve a rebreathing method for estimating mixed venous CO2 content and to apply it to some cases of pneumothorax (1933,2; 1935,1). The results remained only partially satisfactory, which led Cournand and Richards, some eight years later, to develop the method of right heart catheterization in order to obtain direct samples of mixed venous blood as it enters the lung. In the meantime they directed their attention to some problems that had emerged when studying diseased lungs, namely that gases do not mix evenly in the lung, particularly in cases with pulmonary emphysema (1937,1,2). An important series of studies were undertaken in collaboration with Robert Darling, who developed a breath-by-breath analysis of intrapulmonary mixing of inspired air, introducing the simple method of washing out intrapulmonary nitrogen through the inhalation of pure O2 (1940,1), a method that has been widely used and further improved by many other investigators. In the normal lung alveolar nitrogen is rapidly washed out, but in emphysematous lungs this is much slower because nitrogen is retained in the enlarged air spaces. In subjecting the closed-circuit method for estimating residual air volume mentioned above to a systematic critique (1940,2), they concluded that its failure was due to unequal distribution of gases within the lung. To overcome these shortcomings, a new open-circuit method with pure oxygen breathing was introduced (1940,3) that had theoretical advantages but still did not solve all the problems. At the time, these systematic studies of pulmonary ventilatory function, in which Cournand, Darling, and Richards themselves served as the normal subjects, made a very significant con-

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Biographical Memoirs tribution to the advance of clinical respiratory physiology (1941,6). With these methods in hand, Cournand and Richards proceeded to a systematic study of pulmonary insufficiency, which they classified according to the prevailing ventilatory, respiratory (i.e., gas exchange), or cardiocirculatory disturbances (1941,2). They developed the tests by which to differentiate between these functional disturbances. The efficiency of alveolar ventilation, studied at the time by several other groups, was combined with the measurement of arterial O2 saturation as a test for adequate matching of alveolar ventilation with capillary perfusion. It is of historic interest that two papers of this series (1941,3,4) use these concepts and tests to estimate the effects on “pulmonocirculatory” function of various types of collapse therapy: in the late 1930s pulmonary tuberculosis was still a major disease, and collapse therapy was one of the major modes of treatment. THE BREAKTHROUGH: CARDIAC CATHETERIZATION In reflecting in his Nobel lecture on the state of their capabilities at that time, Richards concluded: “We were able to describe the ventilatory functions of the lung and . . . to define to some extent the mixing and the diffusional aspects of pulmonary alveolar or alveolar-capillary functions. But we still could not measure blood flow through the lungs and could not, therefore, move into those broader concepts of cardiopulmonary function which now began to be our goal.” The problem still was how to obtain adequate samples of mixed venous blood to reliably apply the Fick principle. In 1936 Cournand and Richards decided that the only way of securing such samples was to introduce a catheter from a peripheral vein into the right atrium. They knew that this technique had been used in animals since

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Biographical Memoirs the pioneering work of Claude Bernard in 1846 and that the young German surgeon Werner Forssmann had, in a heroic self-experiment in 1929, introduced a thin ureteral catheter into his own right atrium from an arm vein, but yet the procedure was not considered safe for human application. In order to assess the question of risk, Cournand went to Paris, where a former medical teacher of his, Dr. P. Ameuille, had introduced a catheter from an arm vein toward the right atrium in over 100 cases in view of introducing radio-opaque contrast medium for visualization of pulmonary vasculature. “I reviewed all the cases and returned to New York persuaded that cardiac catheterization could be used safely and would meet our needs,” Cournand writes in his autobiography. He then reports that for the next four years, in collaboration with Robert Darling, he carried out experiments in dogs and one chimpanzee and “adapted Bernard's method” to their problem of obtaining samples of mixed venous blood for estimating O2 and CO2 concentrations. It is said that Cournand and Richards also tried the catheterization technique on human cadavers, but there is no mention of this in the published record. Finally in 1941 Cournand and Hilmert Ranges published a note on “Catheterization of the Right Auricle in Man” (1941,1), detailing the technique already developed to near perfection and assessing the possible effects of the catheter on blood and heart function; the catheter was left in position fifteen to sixty minutes and no ill effects were found. They obtained mixed venous samples and could report the calculation of cardiac output by the Fick principle in one case. That was a breakthrough. Cournand did not invent cardiac catheterization, as is often said; his first paper on the method starts out as follows: “Forssmann first used catheterization of the right heart on himself” (1941,1). But he perfected the technique for safe and widespread use in

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Biographical Memoirs humans, even in severely ill patients, and thus brought it to fruition; more importantly still, he pioneered the use of this method by obtaining the first significant measurements of cardiopulmonary function in health and disease. Cardiopulmonary physiology was different after that. The paper of Cournand and Ranges is based on eight catheterizations in four cases of which the first one was catheterized on October 25, 1940. The third patient, considered normal with respect to the heart and lung, was catheterized three times in December, with the most comprehensive set of measurements performed on New Year's Eve 1940. In May 1941 Richards and Cournand presented their estimations of right atrial blood pressure, mostly based on the study of the same cases (1941,5), and on January 6, 1942, a paper (1942,1) was accepted by the American Journal of Physiology that reported in detail in these and some additional cases the direct measurement of the blood pressure in the right auricle and in peripheral veins, demonstrating the rise in atrial pressure in right heart failure. In this paper they also reported on some of the results of their preliminary animal studies. The first measurements were done with saline manometers; improved recordings of the actual pressure waves were obtained a few years later when the catheter was connected to a Hamilton manometer, a technique introduced by Stanley Bradley from the group of Homer Smith at New York University (1944,2). On December 2, 1941, a paper by Cournand, Ranges, and Richard L. Riley was published in the Journal of Clinical Investigation (1942,2) that reported on twenty-one estimations of cardiac output by the direct Fick method. Using both O2 uptake and CO2 discharge, excellent agreement between the estimates was obtained in all cases. When on June 27, 1944, a much extended study was submitted for publication (1945,1), the group had reportedly performed

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Biographical Memoirs some 260 catheterizations on humans, and they had introduced many improvements in their methods of analysis. The resulting estimates of cardiac output were very consistent and consequently appeared definitive. With these studies the great value as well as the safety and feasibility of catheterization of the right heart were established. Some small but ingenious technical details contributed to the success: the catheter tip was given a curve to allow better positioning, and a double lumen catheter was constructed for simultaneous pressure recording or blood sampling from two serial points along the bloodstream (1945,2); a special needle for arterial blood sampling (the “Cournand needle”) was designed. But, most importantly, a battery of physiological methods was set up to obtain the most reliable measurements of blood gases and of pressures. It is the whole concept of an analytical system that set the precedents just as much as the ingenuity of probing the heart with a fine catheter. PHYSIOLOGICAL CONTRIBUTIONS WITH THE CARDIAC CATHETER Cournand and Richards were now ready to approach questions of the pathophysiology of pulmonary circulation. The first condition that imposed itself was traumatic shock, a most pressing problem in those years of World War II with its many casualties in the U.S. armed forces that had just entered combat. The foremost problem of shock is hemodynamic deterioration due to severe blood loss. In the shock unit set up at Bellevue Hospital, cardiac catheterization was used to show that with about half the blood volume lost cardiac output became critically depressed, with the result that shock worsened; also, the importance of variable reduction in peripheral blood flow, particularly to the kidneys, was elucidated by Stanley E. Bradley. Most importantly,

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Biographical Memoirs With D. W. Richards. Pulmonary insufficiency. II. The effects of various types of collapse therapy upon cardiopulmonary function. Am. Rev. Tbc. 44:123. With D. W. Richards and H. C. Maier. Pulmonary insufficiency. III. Cases demonstrating advanced cardiopulmonary insufficiency following artificial pneumothorax and thoracoplasty . Am. Rev. Tbc. 44:272. With D. W. Richards, R. C. Darling, and W. H. Gillespie. Pressure in the right auricle of man, in normal subjects and in patients with congestive heart failure. Trans. Assoc. Am. Physicians 56:218. With E. deF. Baldwin, R. C. Darling, and D. W. Richards. Studies on intrapulmonary mixture of gases. IV. The significance of the pulmonary emptying rate and a simplified open circuit measurement of residual air. J. Clin. Invest. 20:681. 1942 With D. W. Richards, R. C. Darling, W. H. Gillespie, and E. deF. Baldwin. Pressure of blood in the right auricle, in animals and in man: Under normal conditions and in right heart failure. Am. J. Physiol. 136:115. With H. A. Ranges and R. L. Riley. Comparison of results of the normal ballistocardiogram and a direct Fick method in measuring the cardiac output in man. J. Clin. Invest. 21:287. With C. W. Lester and R. L. Riley. Pulmonary function after pneumonectomy in children. J. Thorac. Surg. 11:529. With F. B. Berry. The effect of pneumonectomy upon cardiopulmonary function in adult patients. Ann. Surg. 116:532. 1943 With H. C. Maier. Studies of the arterial oxygen saturation in the postoperative period after pulmonary resection. Surgery 13:199. With R. L. Riley, S. E. Bradley, E. S. Breed, R. P. Noble, H. D. Lauson, M. I. Gregersen, and D. W. Richards. Studies of the circulation in clinical shock. Surgery 13:964. 1944 With R. C. Darling and D. W. Richards. Studies on intrapulmonary mixture of gases. V. Forms of inadequate ventilation in normal

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Biographical Memoirs and emphysematous lungs, analyzed by means of breathing pure oxygen . J. Clin. Invest. 23:55. With H. D. Lauson, R. A. Bloomfield, E. S. Breed, and E. deF. Baldwin. Recording of right heart pressures in man. Proc. Soc. Exp. Biol. Med. 55:34. With H. D. Lauson and S. E. Bradley. The renal circulation shock. J. Clin. Invest. 23:381. With R. P. Noble, E. S. Breed, H. D. Lauson, E. deF. Baldwin, G. B. Pinchot, and D. W. Richards. Chemical, clinical, and immunological studies on the products of human plasma fractionation. VIII. Clinical use of concentrated human serum albumin in shock, and comparison with whole blood and with rapid saline infusion. J. Clin. Invest. 23:491. 1945 With R. L. Riley, E. S. Breed, E. deF. Baldwin, and D. W. Richards. Measurement of cardiac output in man using the technique of catheterization of the right auricle or ventricle. J. Clin. Invest. 24:106. With R. A. Bloomfield and H. D. Lauson. Double lumen catheter for intravenous and intracardiac blood sampling and pressure recording. Proc. Soc. Exp. Biol. Med. 60:73. 1946 With R. A. Bloomfield, H. D. Lauson, E. S. Breed, and D. W. Richards. Recording of right heart pressures in normal subjects and in patients with chronic pulmonary disease and various types of cardiocirculatory disease. J. Clin. Invest. 25:639. With H. D. Lauson and R. A. Bloomfield. The influence of the respiration on the circulation in man: With special reference to pressures in the right auricle, right ventricle, femoral artery and peripheral veins. Am. J. Med. 1:315. With H. L. Motley, A. Himmelstein, D. Dresdale, and D. W. Richards. Latent period between electrical and pressure pulse waves corresponding to right auricular systole. Proc. Soc. Exp. Biol. Med. 63:148. 1947 With A. Lowell and D. W. Richards. Changes in plasma volume and mean arterial pressure after the intravenous injection of concen-

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Biographical Memoirs trated human serum albumin in 38 patients with oligemia and hypotension . Surgery 22:442. Recent observations on the dynamics of the pulmonary circulation. Bull. N.Y. Acad. Med. 23:27. With H. L. Motley, L. Werkö, D. Dresdale, A. Himmelstein, and D. W. Richards. Intravascular and intracardiac pressure recording in man: Electrical apparatus compared with the Hamilton manometer. Proc. Soc. Exp. Biol. Med. 64:241. With H. L. Motley, L. Werkö, A. Himmelstein, and D. Dresdale. The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am. J. Physiol. 150:315. With H. L. Motley, A. Himmelstein, D. Dresdale, and J. Baldwin. Recording of blood pressure from the left auricle and the pulmonary veins in human subjects with interauricular septal defect. Am. J. Physiol. 150:267. With H. L. Motley, L. Werkö, and D. W. Richards. Observations on the clinical use of intermittent positive pressure . J. Aviat. Med. 18:417. 1948 With H. L. Motley, L. Werkö, and D. W. Richards. Physiological studies of the effects of intermittent positive pressure breathing on cardiac output in man. Am. J. Physiol. 152:162. With R. L. Riley, A. Himmelstein, H. L. Motley, and H. M. Weiner. Studies of the pulmonary circulation at rest and during exercise in normal individuals and in patients with chronic pulmonary disease . Am. J. Physiol. 152:372. With W. F. Hamilton, R. L. Riley, A. M. Attyah, D. M. Fowell, A. Himmelstein, R. P. Noble, J. W. Remington, D. W. Richards, N.C. Wheeler, and A. C. Witham. Comparison of the Fick and dye injection methods of measuring the cardiac output in man. Am. J. Physiol. 153:309. With E. deF. Baldwin and D. W. Richards. Pulmonary insufficiency. I. Physiological classification, clinical methods of analysis, standard values in normal subjects. Medicine 27:243. With M. I. Ferrer, R. M. Harvey, L. Werkö, D. T. Dresdale, and D. W. Richards. Some effects of quinidine sulfate on the heart and circulation in man. Am. Heart J. 36:816.

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Biographical Memoirs 1949 With D. G. Green, E. deF. Baldwin, J. S. Baldwin, A. Himmelstein, and C. E. Roh. Pure congenital pulmonary stenosis and idiopathic congenital dilatation of the pulmonary artery. Am. J. Med.. With B. Coblentz, R. M. Harvey, M. I. Ferrer, and D. W. Richards. The relationship between electrical and mechanical events in the cardiac cycle of man. Br. Heart J. 11:1. With E. deF. Baldwin and D. W. Richards. Pulmonary insufficiency. II. A study of thirty-nine cases of pulmonary fibrosis. Medicine 28:1. With M. I. Ferrer, R. M. Harvey, H. M. Weiner, and R. T. Cathcart. Hemodynamic studies in two cases of Wolff-Parkinson-White syndrome with paroxysmal AV nodal tachycardia. Am. J. Med. 6:725. With E. deF. Baldwin and D. W. Richards. Pulmonary insufficiency. III. A study of 122 cases of chronic pulmonary emphysema. Medicine 28:201. With R. L. Riley. “Ideal” alveolar air and the analysis of ventilation-perfusion relationships in the lungs. J. Appl. Physiol. 1:825. With R. M. Harvey, M. I. Ferrer, R. T. Cathcart, and D. W. Richards. Some effects of digoxin upon the heart and circulation in man: Digoxin in left ventricular failure. Am. J. Med. 7:439. With R. L. Riley, R. Austrian, K. W. Donald, and A. Himmelstein. Studies of pulmonary circulation and gas exchange in 3 cases following the resolution of various diffuse miliary infiltrations of the lungs . Trans. Assoc. Am. Physicians 62:134. 1950 With R. L. Riley, A. Himmelstein, and R. Austrian. Pulmonary circulation and alveolar ventilation-perfusion relationships after pneumonectomy. J. Thorac. Surg. 19:80. With M. I. Ferrer, R. M. Harvey, R. T. Cathcart, C. A. Webster, and D. W. Richards. Some effects of digoxin upon the heart and circulation in man: Digoxin in chronic cor pulmonale. Circulation. With J. B. Johnson, M. I. Ferrer, and J. R. West. The relation between electrocardiographic evidence of right ventricular hypertrophy and pulmonary arterial pressure in patients with chronic pulmonary disease. Circulation 1:536.

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Biographical Memoirs With R. E. Johnson, P. Wermer, and M. Kuschner. Intermittent reversal of flow in a case of patent ductus arteriosus: A physiologic study with autopsy findings. Circulation 1:1293. The Fourth Walter Wile Hamburger Memorial Lecture, Institute of Medicine of Chicago: Some aspects of the pulmonary circulation in normal man and in chronic cardiopulmonary diseases. Circulation 2:641. With E. deF. Baldwin, K. A. Harden, D. G. Greene, and D. W. Richards. Pulmonary insufficiency. IV. A study of 16 cases of large pulmonary cysts or bullae. Medicine 29:169. 1951 With D. Carroll, J. McClement, and A. Himmelstein. Pulmonary function following decortication of the lung. Am. Rev. Tbc. 63:231. With J. R. West, J. H. McClement, D. Carroll, H. A. Bliss, M. Kuschner, and D. W. Richards. Effects of cortisone and ACTH in cases of chronic pulmonary disease with impairment of alveolar-capillary diffusion. Am. J. Med. 10:156. With J. R. West, E. deF. Baldwin, and D. W. Richards. Physiopathologic aspects of chronic pulmonary emphysema. Am. J. Med. 10:481. With J. K. Alexander. M. I. Ferrer, and R. M. Harvey. The Q-T interval in chronic cor pulmonale. Circulation 3:733. With R. M. Harvey, M. I. Ferrer, and D. W. Richards. Influence of chronic pulmonary disease on the heart and circulation . Am. J. Med. 10:719. With R. Austrian, J. H. McClement, A. D. Renzetti, K. W. Donald, R. L. Riley. Clinical and physiologic features of some types of pulmonary diseases with impairment of alveolar-capillary diffusion: The syndrome of “alveolar-capillary block.”Am. J. Med. 11:667. With R. L. Riley. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: Theory. J. Appl. Physiol. 4:77. With R. L. Riley and K. W. Donald. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: Methods. J. Appl. Physiol. 4:102. 1952 With K. W. Donald, A. Renzetti, and R. L. Riley. Analysis of factors

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Biographical Memoirs affecting concentration of oxygen and carbon dioxide in gas and blood of lungs: Results. J. Appl. Physiol. 4:497. With A. Himmelstein. Cardiac catheterization in the study of congenital cardiovascular anomalies: An evaluation. Am. J. Med. 12:349. With A. P. Fishman, J. McClement, and A. Himmelstein. Effects of acute anoxia on the circulation and respiration in patients with chronic pulmonary disease studied during the “steady state.” J. Clin. Invest. 31:770. With M. I. Ferrer, R. M. Harvey, R. T. Cathcart, and D. W. Richards. Hemodynamic studies in rheumatic heart disease. Circulation 6:688. Cardiopulmonary function in chronic pulmonary disease. In The Harvey Lecture Series vol. 46. Springfield, Illinois:Chals C. Thomas.. 1953 With M. I. Ferrer, R. M. Harvey, M. Kuschner, and D. W. Richards. Hemodynamic studies in tricuspid stenosis of rheumatic origin. Circ. Res. 1:49. With J. H. McClement, A. D. Renzetti, and A. Himmelstein. Cardiopulmonary function in the pulmonary form of Boeck's sarcoid and its modification by cortisone therapy. Am. Rev. Tbc. 67:154. With A. P. Fishman. Heart. Ann. Rev. Physiol. 15:247. With R. M. Harvey and M. I. Ferrer. The treatment of chronic cor pulmonale. Circulation 7:932. With R. M. Harvey, M. I. Ferrer, R. T. Cathcart, and D. W. Richards. Mechanical and myocardial factors in chronic constrictive pericarditis . Circulation 8:695. 1954 With R. A. Bader, M. E. Bader, and S. W. Kim. Comparative studies, in normotensive man, of the effectiveness, retention, and elimination of various plasma expanders. Surgery 35:366. With D. W. Richards, R. A. Bader, M. E. Bader, and A. P. Fishman. The oxygen cost of breathing. Trans. Assoc. Am. Physicians 67:162. 1955 With A. M. Mitchell. The fate of circulating lactic acid in the human lung. J. Clin. Invest. 34:471. With R. M. Harvey, M. I. Ferrer, P. Samet, R. A. Bader, M. E. Bader,

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Biographical Memoirs and D. W. Richards. Mechanical and myocardial factors in rheumatic heart disease with mitral stenosis. Circulation 11:531. With A. P. Fishman, A. Himmelstein, and H. W. Fritts. Blood flow through each lung in man during unilateral hypoxia. J. Clin. Invest. 34:637. With M. I. Ferrer, R. M. Harvey, R. H. Wylie, A. Himmelstein, A. Lambert, M. Kuschner, and D. W. Richards. Circulatory effects of mitral commissurotomy with particular reference to selection of patients for surgery. Circulation 12:7. With A. P. Fishman and P. Samet. Ventilatory drive in chronic pulmonary emphysema. Am. J. Med. 19:533. The mysterious influence of unilateral pulmonary hypoxia upon the circulation in man. Acta Cardiol. 10:429. 1956 With O. L. Wade, P. Combes, A. W. Childs, H. O. Wheeler, and S. E. Bradley. The effect of exercise on the splanchnic blood flow and splanchnic blood volume in normal man. Clin. Sci. 15:457. With E. Braunwald and A. P. Fishman. Time relationship of dynamic events in the cardiac chambers, pulmonary artery and aorta in man. Circ. Res. 4:100. With P. Harris, H. W. Fritts, R. H. Clauss, and J. E. Odell. Influence of acetylcholine on human pulmonary circulation under normal and hypoxic conditions. Proc. Soc. Exp. Biol. Med. 93:77. 1957 With P. Samet, H. W. Fritts, and A. P. Fishman. The blood volume in heart disease. Medicine 36:211. With H. W. Fritts, P. Harris, C. A. Chidsey III, and R. H. Clauss. Validation of a method for measuring the output of the right ventricle in man by inscription of dye-dilution curves from the pulmonary artery . J. Appl. Physiol. 11:362. Pulmonary circulation. Its control in man, with some remarks on methodology . Am. Heart J. 54:172. Pulmonary circulation: Its control in man, with some remarks on methodology . (Nobel lecture.) Science 125:1231. Control of the pulmonary circulation in man with some remarks on methodology. In Les Priz Nobel en 1956, p. 196. Stockholm : Norstedt & Söner.

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Biographical Memoirs 1958 With H. W. Fritts, P. Harris, R. H. Clauss, and J. E. Odell. The effect of acetylcholine on the human pulmonary circulation under normal and hypoxic conditions. J. Clin. Invest. 37:99 With A. Himmelstein, P. Harris, and H. W. Fritts. Effect of severe unilateral hypoxia on the partition of pulmonary blood flow in man. J. Thorac. Surg. 36:369. With H. W. Fritts. The application of the Fick principle to the measurement of pulmonary blood flow. Proc. Natl. Acad. Sci. USA 44:1079. With E. Braunwald and A. P. Fishman. Estimation of volume of a circulatory model by the Hamilton and the Bradley methods at varying flow/volume ratios. J. Appl. Physiol. 12:445. 1959 With C. A. Chidsey III, H. W. Fritts, A. Hardewig, and D. W. Richards. Fate of radioactive krypton (Kr85) introduced intravenously in man. J. Appl. Physiol. 14:63. With W. A. Briscoe. Uneven ventilation of normal and diseased lungs studied by an open-circuit method. J. Appl. Physiol. 14:284. With H. W. Fritts, J. Filler, and A. P. Fishman. The efficiency of ventilation during voluntary hyperpnea: Studies in normal subjects and in dyspneic patients with either chronic pulmonary emphysema or obesity. J. Clin. Invest. 38:1339. 1960 With P. Harris and H. W. Fritts. Some circulatory effects of 5-hydroxytryptamine in man. Circulation 421:1134. With H. P. Gurtner and W. A. Briscoe. Studies of the ventilation-perfusion relationships in the lungs of subjects with chronic pulmonary emphysema, following a single intravenous injection of radioactive krypton (Kr85). I. Presentation and validation of a theoretical model. J. Clin. Invest. 39:1080. With A. P. Fishman and H. W. Fritts. Effects of acute hypoxia and exercise on the pulmonary circulation . Circulation 22:204. With A. P. Fishman and H. W. Fritts. Effects of breathing carbon dioxide upon the pulmonary circulation . Circulation 22:220. With W. A. Briscoe, E. M. Cree, J. Filler, and H. E. J. Houssay. Lung

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Biographical Memoirs volume, alveolar ventilation and perfusion interrelationships in chronic pulmonary emphysema. J. Appl. Physiol. 15:785. With L. Donato, J. Durand, D. F. Rochester, J. O. Parker, R. M. Harvey, and M. L. Lewis. Separate performance of both ventricles in man during the early phase of exercise, as analyzed by the method of selective radiocardiography . Trans. Assoc. Am. Physicians 73:283. With G. P. Zocche and H. W. Fritts. Fraction of maximum breathing capacity available for prolonged hyperventilation . J. Appl. Physiol. 15:1073. With H. W. Fritts, A. Hardewig, D. F. Rochester, and J. Durand. Estimation of pulmonary arteriovenous shunt-flow using intravenous injections of T-1824 dye and Kr85 . J. Clin. Invest. 39:1841. 1961 With G. Emmanuel and W. A. Briscoe. A method for the determination of the volume of air in the lungs: Measurements in chronic pulmonary emphysema. J. Clin. Invest. 40:329. With H. W. Fritts, P. Harris, C. A. Chidsey III, and R. H. Clauss. Estimation of flow through bronchial-pulmonary vascular anastomoses with use of T-1824 dye. Circulation 23:390. With H. W. Fritts and D. W. Richards. Oxygen consumption of tissues in the human lung. Science 133:1070. 1962 With Y. Enson, W. A. Briscoe, and M. L. Polanyi. In vivo studies with an intravascular and intracardiac reflection oximeter. J. Appl. Physiol. 17:552. With L. Donato, C. Giuntini, M. L. Lewis, J. Durand, D. F. Rochester, and R. M. Harvey. Quantitative radiocardiography. I. Theoretical considerations. Circulation 26:174. With M. L. Lewis, C. Giuntini, L. Donato, and R. M. Harvey. Quantitative radiocardiography. III. Results and validation of theory and method. Circulation 26:189. 1963 With H. W. Fritts, B. Strauss, and W. Wichern. Utilization of oxygen in the lungs of patients with diffuse, non-obstructive pulmonary disease. Trans. Assoc. Am. Physicians 76:302.

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Biographical Memoirs 1964 With Y. Enson and A. G. Jameson. Intracardiac oximetry in congenital heart disease. Circulation 29:499. Air and blood. In Circulation: Men and Ideas, eds. A. Fishman and D. W. Richards, p. 3. New York : Oxford University Press. 1965 With P. R. B. Caldwell and H. W. Fritts. Oxyhemoglobin dissociation curve in liver disease. J. Appl. Physiol. 20:316. With N. A. Lassen, H. W. Fritts, P. R. B. Caldwell, C. Giuntini, and W. Dansgaard. Intrapulmonary exchange of the stable isotope 18O2 injected intravenously in man. J. Appl. Physiol. 20:809. 1970 With H. Zuckerman. The code of science: Analysis and some reflections on its future. Stud. gen. 23:941. Also in Knowledge in Search of Understanding: The Frensham Pond Papers, ed. P. A. Weiss, p. 126. New York : Futura Publishing Company, 1975. 1971 Prospective philosophy and methods: Some reflections on their preliminary application to medical education. Futures (December):372. Applications of prospective thinking and method to medical education; The initial results of a practical experiment. Stud. gen. 24:1405. 1973 With M. Meyer. Overcrowding, a disease of social growth. Futures (June):287. With M. Levy (eds.) . Shaping the Future: Gaston Berger and the Concept of Prospective. London : Gordon & Breach. Dickinson Woodruff Richards: 1895-1973. Trans. Assoc. Am. Physicians 86:33. On the codes of science and scientists. In Proceedings of the Third International Conference—From Theoretical Physics to Biology, p. 436. Basel : S. Karger. 1975 Cardiac catheterization: Development of the technique, its contributions to experimental medicine, and its initial applications in

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Biographical Memoirs man (edited and expanded version of the Jimenez Diaz Memorial Lecture, 1970). Acta Med. Scand. (Suppl.) 579:1. 1976 With M. Meyer. The scientist's role. Minerva 14:80. 1977 The code of the scientist and its relationship to ethics. Science 198:699. 1979 Claude Bernard's contributions to cardiac physiology , In Claude Bernard and the Internal Environment, a Memorial Symposium, ed. E. D. Robin, p. 97. New York : Marcel Dekker. 1980 Historical details of Claude Bernard's invention of a technique for measuring the temperature and the pressure of the blood within the cavities of the heart. In Science and Social Structure: A Festschrift for Robert Merton . Trans. N.Y. Acad. Sci., p. 1. 1981 Science in service of society. The Sciences 21:7. 1985 Special lecture: Origin and historical development of clinical physiology in pulmonary disease. Bull. Eur. Physiopathol. Respir. 21:205. 1986 Dickinson Woodruff Richards, 1895-1973. Biographical Memoirs, vol. 57, p. 459. Washington, D.C. : National Academy Press.