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CARL JOHN WIGGERS May 28, 1 883-A pril 29, 1963 BY EUGENE M. LANDIS WHENEVER HISTORIANS of science deal with the development of physiology and medicine in the United States, they give special significance to the period 1900-1950. At the turn of the century, physiology was beginning its growth in this country as a science in its own right and as a discipline useful to medicine and surgery. The life and contributions of Carl John Wiggers coincide almost precisely with this period. In 1901 he entered medical school with the customary aim of becoming a physician. Almost at once he attracted the attention of his professors in the preclinical sciences. Stimulated and encouraged by them, he became interested in physiological research and enhanced that interest by advanced study abroad. Upon his return to the United States, he became a member of a small but important group of leaders who developed highly individual and produc- tive research laboratories in several medical schools and in several specialties of physiology. Carl Wiggers's chief location was the medical school of Western Reserve University for thirty-five years (1918-1953), and his lifelong interest was cardiovascular physiology. Two generations of physiologists and clinicians were stimulated to follow research careers because of his influence as teacher, pre- ceptor in research, lecturer, author, and editor. He was promi- nent among those who formulated the physiological principles 363
364 BIOGRAPHICAL MEMOIRS that underlie many of the recent, often spectacular, advances in the diagnosis and treatment of cardiovascular diseases. He was elected a member of the National Academy of Sciences in 1951. Carl John Wiggers was born in Davenport, Iowa, on May 28, 1883. He was the first of two children; a younger sister died in childhood. His father, Jurgen Wiggers, accompanied by a brother, John, had left the limited prospects of a small family farm in the duchy of Holstein to seek opportunity in this country. To pay their passage across the Atlantic, they served as sailors and in 1876 arrived in New York as immigrants. Jurgen, during a period of orientation, worked his way west as far as Colorado through temporary farm jobs and even some unsuccessful prospecting for gold. He subsequently returned eastward to Scott County, Iowa, and settled in Davenport. There, in 1882, he met and married Anna Margaretha Kundel, whose family had also emigrated from Holstein. Eventually, Jurgen Wiggers became manager of a social club called Lahr- mann's Halle, which resembled the celebrated Ratskellern of Germany and was a favorite rendezvous of professional and busi- ness men in the downtown area of Davenport. In his autobiog- raphy Carl Wiggers describes how his father, while still in Holstein, had aspired to an education in law or even medicine. For the father these ambitions could not be fulfilled; but the son received parental encouragement for education toward a profession, in addition to the usual German domestic traditions and thrift. Carl Wiggers attended elementary and high schools in Dav- enport. Before he went to high school, his parents required that he have in mind aims for a specific vocation or profession. To keep within the family's limited resources, he chose pharmacy. In high school his teachers of chemistry, physics, and zoology provided special stimulation to young Wiggers; and he, an eager student, proved especially interesting to them. They took
CARL J OHN WIGGERS 365 "every opportunity to discuss his future aspirations and tactfully awakened the idea" that he should aim for medicine rather than pharmacy. In a carefully reasoned comparison between the newer Johns Hopkins medical school (college degree required) and the slightly older medical school of the University of Michi- gan (high school diploma then still sufficient), Wiggers chose the latter. In his choice he noted that he really couldn't afford four years of college, that the organization and curricula of the two schools seemed similar, and, more significantly, that Johns Hopkins, in developing its own medical faculty, had, in fact, chosen three of its professors from Michigan's faculty. Early in medical school at Ann Arbor, Wiggers must have shown again some qualities that attracted the immediate inter- est of his first professors. His initial intentions to prepare for public health work, or for practice in obstetrics and pediatrics, gave way to curiosity concerning physiology and research. He ascribed this change, first, to an "experiment in education" by Professor Warren P. Lombard, which involved a "research problem" assigned to students in the final weeks of their course in physiology. Second, this was followed by Professor Arthur A. Cushny's emphasis on the physiological actions of drugs. And, third, Lombard offered Wiggers a paid student assistantship in physiology that continued until he received his M.D. in 1906. He was then promoted to an instructorship in physiology, which he held from 1907 to 1911. His publications began while he was a medical student. In 1905 he described the action of adrenalin on the cerebral blood vessels and demonstrated his findings at the American Physio- logical Society meeting in Ann Arbor that same year. At this meeting he also heard reports and observed demonstrations by well-known investigators such as Macleod, Brodie, Erlanger, and Y. Henderson. By his own account the stimulation from infor- mal conversations with these and other physiologists firmly established his interest in physiology as a career. In the thirteen
366 BIOGRAPHICAL MEMOIRS papers that Wiggers published from 1905 to 191 1, he described the responses of cerebral, coronary, and pulmonary blood ves- sels to electrical or chemical stimulation; presented an improved apparatus for measuring blood flow; and reported studies on hemorrhage with particular emphasis on the ineffectiveness, or even harmfulness, of adrenalin injections. As a group, these papers present a general preview of areas and topics that Wit ers continued to study in greater depth for forty years. His chief lifelong interest, cardiac physiology, became obvious several years later. In 1907 Carl Wipers married Minerva E. Berry, a junior medical student and thus, as he worded it, "two careersone scientific, the other domesticwere launched almost simulta- neously," and their "coexistence proved facilitatory and salu- tary." This was verified many times over by his wife's assistance as part-time secretary and by her understanding companionship and help during long hours of research and writing. They had two sons, both of whom became eminent. One, Harold, became himself a Professor of Physiology and later, in 1953, Dean of Medicine at Albany Medical College. The other, Raymond, entered the field of industrial advertising and became an award winner in that area. In later years a lifelong habit of hospitality and personal interest enlarged the social boundaries of the Wiggers family and home to include research fellows, junior staff members, colleagues, and visitors from other laboratories and countries. It is significant that in 1952 the affection of this larger family was expressed by their establishing at Western Reserve University a joint honor entitled "The Minerva and Carl Wiggers Annual Prize in Physiology." In 1907, during his first year as an Instructor, Wiggers was given the responsibility for a didactic and demonstration course in physiology for dental students, who had become seriously discontented with Professor Lombard's offerings. In this first course, he revealed his conviction that, if subject matter was
CARL JOHN WIGGERS 367 chosen wisely, basic courses could be made not only valuable to students but also interesting. In describing the results of this first responsibility for teaching, he made the modest and gently humorous appraisal that "the attitude of dental students toward physiology was changed; it no longer was regarded as an ordeal but as a satisfaction, if not exactly a pleasure." The course led to the publication in 1914 of his first book, ~4 Brief Text of Physiology. An important career decision was made by Wiggers early in his instructorship. To supplement their low salaries, members of basic science departments were allowed, and even encouraged, to engage in limited practice of medicine. A brief test of such part-time clinical work led him to conclude that it was hinder- ing, not helping, his academic career, and reinforced his deci- sion to make physiology his sole activity. In 1910 Professor Lombard took a sabbatical year to study abroad, and Wiggers became acting head of the department. He mentioned later that it was helpful to learn at an early age the nature of administra- tive work. At this time, with the advice of A. W. Hewlett, the new Professor of Medicine, he used some hours in the basic physiology course to demonstrate to first-year students how physiologic information could be applied to clinical problems and help interpret the signs and symptoms of disease in patients. During this period Wiggers found that his studies were being limited by the unreliability of the pressure recorclers then available to physiologists. Professor Hewlett told him of the optical recording methods devised by Professor Otto Frank in Munich, and Wiggers promptly arranged, through Lombard, then in Europe, for a year of study abroad. But this had to be postponed to 1912 and abbreviated to a spring and summer be- cause, on the recommendation of W. H. Howell of Johns Hopkins, Graham Lusk invited him to come to Cornell Medical School in New York as Instructor of Physiology. It was agreed, however, that after a few months at Cornell, he would have a
368 BIOGRAPHICAL MEMOIRS leave of absence for study with Professor Frank at the Physio- logical Institute of Ludwig-Maximilian University. Arriving there in May 1912, Wiggers found that, as a representative of Lusk's group, he was granted exceptional privileges in observing the optical equipment and methods that the usually reserved, even secretive, Otto Frank was developing in his laboratory for measuring rapidly and accurately not only blood pressures, but also pulse contours and rates of blood flow. By some additional visits elsewhere, Wiggers also gained a "traveller's acquaintance with other laboratories in Europe." When Wiggers returned to New York in the summer of 1912, his research interests were not limited to physiology, but continued to include cardiovascular disease also. To learn more about the latter, he devoted one morning each week to attend- ing ward rounds in Bellevue Hospital. He kept improving the reflecting mirror manometer of Otto Frank and devised a mobile unit that brought his equipment into use at the bedside. He was promoted to Assistant Professor of Physiology in 1913. His research from 1912 to 1918 dealt with many areas of cardio- vascular function but began to deal increasingly with an analy- sis of cardiac function, normal and abnormal. Early in this period he published the first optically recorded pressure pulses in the pulmonary arteries of dogs through cannulas inserted di- rectly. These records, together with Otto Frank's studies of the central arterial pulse in the aorta, permitted comparisons of pressure levels in the lesser and greater arterial circulations. In 1917 he compared the timing of pressure changes in the heart chambers with the contractions of heart muscle and with the electrocardiogram. He was thus in a position to amplify the findings of Thomas Lewis (later Sir) in London, who was chal- lenging Einthoven's view that the electrical and mechanical events of cardiac contraction were simultaneous. These observa- tions indicated that electrical events preceded the contraction of heart muscle and were a measure of the progressive conduction
CARL JOHN WIGGERS 369 of the excitation process throughout the heart. With clinical co-workers in Bellevue Hospital, he studied atrial fibrillation, analyzed the supraclavicular venous pulse in man, and began registering heart sounds. Even at this early stage he was con- vinced that physiologists should at intervals describe in review form the status of ongoing research in order to keep clinicians well informed. His second book, Modern Aspects of the Circula- tion in Health and Disease, published in 1915, was such a prog- ress report. It was a monograph that described, with examples, the usefulness of newer methods in the clinical diagnosis and treatment of cardiovascular diseases as seen in hospital practice. He was always a vigorous supporter of the view that advances in medicine and surgery must be based upon an investigative and basically physiologic approach to disease. In 1917-1918 the entry of the United States into World War I presented a new series of cardiovascular problems, rang- ing from cardiac-fitness examinations in draftees, through neu- rocirculatory asthenia or "soldier's heart" in stressed individuals, to the physiologic principles underlying the diagnosis and treatment of hemorrhage and shock in the severely wounded. In 1918 Wiggers served on a medical appeal board and used his experience with electrocardiography to help adjudicate in cases of draftees when physical fitness was disputed. At this time, too, he became a member of a National Research Council Committee on Shock. Sir Thomas Lewis invited him to come abroad to share in a study of neurocirculatory asthenia, but he had to decline, chiefly because Graham Lusk was on leave for war research abroad, and again he was acting chairman of a depart- ment. However, as a "Contract Surgeon" in U.S. Army General Hospital #9, he spent a short time during the summer of 1918 in a research laboratory, headed by Professor Francis W. Pea- body from Harvard, for the purpose of studying cardiac dis- abilities in draftees and soldiers. With all this in progress, and during a meeting of the Com-
370 BIOGRAPHICAL MEMOIRS mittee on Shock in Baltimore, Torald Sollman, Professor of Pharmacology at Western Reserve Medical School, told Wiggers that J. I. R. Macleod, then Professor of Physiology at Western Reserve, had decided to accept a position with the University of Toronto, and then urged him to consider accepting the vacant professorship beginning with the autumn term of 1918. Wiggers accepted, but only after making sure that he could arrange matters at Cornell so that Graham Lusk would be inconve- nienced as little as possible by his leaving. Thus in 1918, and at age thirty-five, Wiggers began to estab- lish in Cleveland his own center of cardiovascular research, first in a small loft of the older medical building, and then from 1924 onward, in a separate floor of a new medical building in which the physiology department had more space and facilities as planned by Wiggers himself. The problems of new equip- ment, staff, courses for students, and budgetary matters were burdensome at times but did not perceptibly interrupt his research and publications. During the thirty-five years from 1918 to 1953, almost every part, and almost every physiological function, of the heart and blood vessels were the direct or indi- rect topics of some study by Carl Wiggers or by his many graduate students and co-workers. Approximately 400 papers were published from the laboratories that Wiggers established and supervised. In matters of authorship and credit, he was again characteristically generous. In over half of these papers, his colleagues and students were granted sole authorship. Wig- gers believed firmly that beginning investigators deserved sole authorship of papers dealing with their work, even though the head of a laboratory may have given essential assistance in ideas, advice, and editing. Wiggers also published a total of seven books in editions ranging from one to five. To do justice to the content of all these papers and books is impossible in any brief memoir. It is fortunate that Wiggers wrote in 1958 an autobiography entitled Reminiscences and
CARL J OHN WIGGERS 371 Adventures in Circulation Research. That book provides a de- tailed, chronological account of the questions that prompted his research, his development of suitable equipment, and his ex- periments and results. Descriptions of successes are balanced by frank discussion of failures, oversights, and those second thoughts that increasing experience and new facts produced. In this brief memoir it is more appropriate to describe a few of the main lineages of ideas that determined the major pathways and methods used by Wiggers in his researches. One of the earliest of these lineages dealt with analyzing the interrelations of electrocardiographic, excitatory, contractile, and hemodynamic events during the cardiac cycle. This was not easy, because in the early 1900s it was necessary to import almost all research equipment of any intricacy from instrument makers abroad, and at great expense. When Wiggers began working in Cleveland, conditions were improving, but it was still necessary for him to establish a departmental workshop to produce his own improved optical manometers for recording pressures or sound, as well as cardiometers and flowmeters for volume mea- surements. Moreover, each of these devices had in the past been used separately by individual investigators and usually for lim- ited and special problems. Most difficult of all was the task of obtaining the best possible string galvanometers for electro- cardiography, but this, too, was accomplished. In viewing the · ,= future of cardiac research, Winders saw that: ". . . by aligning such a galvanometer with optical recorders for pressure, muscular contraction and heart sounds, the inter- relations of electric and contractile events in the heart could be determined more accurately than before. This problem was and remainsone of cardiologic as well as scientific interest, for it is basic to the usefulness of electrocardiographic interpretation of impulse conduction." Each of the new instruments presented technical problems, and combining several devices produced a really formidable
372 BIOGRAPHICAL MEMOIRS challenge. Nevertheless, Wiggers collected the data necessary to produce a graphic summary that correlated the dynamic, me- chanical, acoustic, and electrocardiographic events during the normal cardiac cycle, lasting approximately 0.9 seconds. As a chart this summary became a standard textbook figure and was reprinted in reviews and books dealing with physiology, electro- cardiography, and cardiology in general. It is still used as a diagram upon which new data, such as single-cell membrane action potentials, can easily be added. In 1921 Wiggers wished to measure more accurately the effects on the cardiac cycle of changing venous return, as in muscular exercise, and of aortic pressure, as in hypertension. It was necessary to subdivide ventricular systole and diastole into smaller and more precise units. Eventually eight phases were identified: isometric contraction, maximal ejection, reduced ejection, protodiastole, isometric relaxation, rapid inflow, diasta- sis, and atrial systole. The beginning and end of each phase was defined precisely by relevant simultaneous changes of blood pressure levels in the left ventricle, aorta, or atrium; by small, more detailed changes in the configuration of the pressure pulses; and by heart sounds. Also, for each phase, the normal range of duration was measured. This subdivision of the cardiac cycle was also widely used in physiology and cardiology. More- over, from these studies developed a second lineage of problems, ideas, and research. During experiments on the exposed heart, Wiggers had been impressed with its great resistance to drastic manipulations and even injury. "However, it happened far too often that the thrust of a cannula or stylus through the ventricular walls was followed by irreversible fibrillation whose occurrence could not be re- lated to the region involved, the nutrition or dynamic state of the ventricles, or to the age of the animal. The hazard of terminating an experiment by fibrillation was materially in- creased when strong shocks were applied during systole...."
CARL J OHN WIGGERS 373 He tried many expedients to diminish the incidence of ventricu- lar fibrillation but results were discouraging. In the 1920s, as electrical appliances in home and industry became more numerous, so had also the deaths of users by accidental electrocution from faulty wiring. After a "Conference on Electric Shock" in 1929, Professor W. H. Howell of Johns Hopkins asked Carl Wiggers to join efforts with Donald R. Hooker in exploring possible ways of restoring normal rhythm to hearts in which fibrillation had been produced by electric currents. Wiggers accepted, but with the cautious feeling that the most he "could hope for was some discovery that might reduce the mortality rate of experimental animals." His first approach was a screening study to explore chemical methods of restoring normal cardiac rhythm. Although intra- ventricular injections of potassium chloride often made the fibrillating heart quiescent and calcium salts sometimes restored a normal heartbeat, these effects were not consistent enough to be satisfactory, even in experimental animals. After deciding that not enough was known about the genesis of ventricular fibrillation, Wiggers and his group in 1930 used coordinated cinematographic and electrocardiographic methods to study the earliest stages of the arrhythmia, which then emerged as an evolving process that progressed irregularly through four fairly characteristic, but often overlapping, stages. These might take a few to many minutes to develop fully from the first undulating contractions to the fourth, and longest, atonic stage, lasting from twenty to sixty minutes. Because this final atony did not develop when the ventricles were perfused artificially with oxygenated blood, Wiggers suggested that the final lethal flaccidity of un- perfused, fibrillating hearts could "probably be referred to fail- ure to reconstitute energy yielding material during the pro- gressing anoxia." In 1932 Kouwenhoven, Hooker, and Langworthy, while studying the distribution of electric current in the bodies of dogs,
374 BIOGRAPHICAL MEMOIRS tested and confirmed an almost forgotten statement published in 1899 by Prevost and Battelli to the effect that if ventricular fibrillation occurred it could be terminated by applying a strong electric current to the heart. Wiggers had accumulated methods and experience that placed him in an ideal position to provide speedy, additional confirmation of the beneficial effects of countershock, though he found it effective only when applied within two or three minutes after induction of fibrillation. In the meantime, H. B. Williams and associates had also confirmed observations by Wiggers that electric shocks during the "vulner- able period of the heart cycle" induced fibrillation and that immediate application of strong currents to the chest wall could stop that fibrillation. As Wiggers expressed it, the problem became one of "extending the period during which counter- shock could be effective after development of fibrillation." Success in doing this was "not a matter of chance; it resulted from a logical application of observations from contemporane- ous experiments...." These pointed to the conclusion "that the fibrillating ventricles lose their power of effective contrac- tion after 2 or 3 minutes, because they are deprived of oxygen- ated blood. The remedy apparently needed was a supply of oxygen for the myocardium before application of countershock." In 1936 Wiggers suggested that gentle manual rhythmic com- pression of the ventricles be started as quickly as possible to raise arterial blood pressure and to restore blood flow through the coronary vessels in the heart muscle. When this maneuver was continued until vigorous fibrillary movements were re- established, then countershock usually restored coordinated ventricular contractions. In addition, however, dogs with larger hearts often required "serial defibrillation," i.e., administration of three to five brief shocks at intervals of two seconds to reach the deeper lying parts of the ventricular wall. By 1940 he could demonstrate by means of these innovations that a dog could sur- vive if its heart were fibrillated and defibrillated reversibly at will many times in succession. Over a decade elapsed,
CARL JOHN WIGGERS 375 however, before these principles were utilized clinically in the emergency treatment of ventricular fibrillation in patients. Dur- ing this time he and his co-workers continued to study in the laboratory many related topics, including quantitative fibrilla- tion thresholds, fibrillation following induced coronary occlu- sion, effects of type of current and voltage, and actions of drugs. Collectively, these research reports form an essential part of the physiologic foundation that supports modern cardiac resuscita- tion and defibrillation, cardiac monitoring, and pacemakers, as well as the feasibility and relative safety of "elective cardiac arrest" in open-heart surgery. In still another lineage of interlocking experiments, Wig- gers and his students dealt with the hemodynamics and control of blood flow through the heart and past its valves, through a distensible aorta, and through a branching system of peripheral vessels, including especially the coronary arteries in the heart muscle itself. The number and ramifications of these experi- ments defy any brief summary. They included studies on the energetics and biophysics of the heart as a pump, wave forms in the aorta and its branches, and peripheral resistance to blood flow through arteries and arterioles. His interest in abnormal- ities such as valvular lesions, arteriosclerosis, and hemorrhage can be traced back to his instructor days at Michigan, and especially to his hours on the wards of Bellevue Hospital, in New York. His experiments were sometimes analytice.g., cen- tral and peripheral pulse wave forms, factors determining coro- nary blood flow, accuracy of blood pressure measurement in animals and manand sometimes integrativee.g., his classifica- tion of stages in severe hemorrhage and ensuing shock. The wider implications of these integrations are found in his seven books: Modern Aspects of the Circulation in Health and Disease (two editions, 1915 and 1923), Pressure Pulses in the Cardio- vascular System (1928), Principles and Practice of Electrocardi- ography (1929), Physiology in Health and Disease (five editions, 1934 to 1949), Physiology of Shock (1950), Circulatory Dynam-
376 BIOGRAPHICAL MEMOIRS ics: Physiologic Studies (1952), and Reminiscences and Adven- tures in Circulation Research (1958~. In whatever he did Carl Wiggers was always ready to de- scribe clearly and unequivocally his basic principles and con- victions. For instance, he emphasized repeatedly that an ideal department of physiology in a medical school had three main [unctions: first, to offer medical students the broadest possible education in physiology and its importance for medicine; sec- ond, to contribute actively and regularly to physiological knowledge by research; and, third, to educate and train experi- menters and teachers for both physiology and medicine. In the course of accomplishing the first two objectives, as already summarized above, Wiggers provided an exceptionally good environment for the third. In his thirty-five years at Western Reserve, his department provided direct research ex- perience for almost 200 individuals. By 1953 his alumni in- cluded a score of professors of physiology or heads of closely affiliated research laboratories. Among these were research cen- ters, almost as eminent as the parent one, in special topics such as coronary blood flow, membrane action potentials in cardiac muscle, peripheral resistance to regional blood flow, clinical electrocardiography, hemorrhage, and shock. Visiting students came from foreign countries and returned to important posi- tions in physiology or medicine abroad. One of them, Corneille Heymans, from Belgium, received a Nobel Prize in 1930. By conservative estimate almost a hundred young physicians and surgeons held fellowships that gave them direct experience with the principles of physiological research. In most instances this advanced work was related informally to research in progress, but in 1949 Wiggers felt that new conditions made a new train- . . ng procedure appropriate. In 1945, the end of World War II began a period of ex- panded support for research. In addition, by 1947, clinical interest in catheterization technics for early diagnosis and
CARL J OHN WIGGERS 377 treatment of congenital cardiac defects and coronary artery disease was growing faster than the supply of clinical investiga- tors. To meet this need Wiggers proposed a more formal "apprenticeship" program in cardiovascular research and writ- ing. Under the joint sponsorship of the American Heart Asso- ciation and the U.S. Public Health Service, and with the facilities in his laboratories, he and his staff graduated about twenty "U.S.P.H.S. Training Course Fellows" during the three years from 1949 to 1952. These graduates brought to a number of new clinical cardiology centers the skills and judgment of . . . experienced ~ Investigators. In developing this apprenticeship program, Wiggers empha- sized still another of his basic principles, namely that any research effort is not complete until the results are carefully written, thoroughly edited, and promptly published in a form that is both clear and useful to others. With characteristic humor he describes in his reminiscences how the critiques of his own first papers in 1905 by Professor W. P. Lombard seemed devastating temporarily and then helpful eventually. In 1925 Wiggers shared in founding the American Heart Journal, was a member of the original Advisory Editorial Board, and remained a member until 1937. In 1952 he was only a year away from retirement and accepted still another editorial challenge. The American Heart Association had adopted a policy of increasing support for basic research and found it timely to publish a new journal that could emphasize a multidisciplinary approach to fundamental studies of the cardiovascular system. Wiggers was asked to organize and edit this new journal, Circulation Re- search, with the first issue scheduled for 1953. He turned over the administration of the Department of Physiology in 1952 to a newly appointed successor, Dr. George Sayers. He then ac- cepted an appointment as Honorary Professor of Physiology with the Frank E. Bunts Educational Institute of Cleveland and organized an editorial office in space provided by the Cleveland
378 BIOGRAPHICAL MEMOIRS Clinic. As the first editor of Circulation Research from 1953 to 1958, he brought the new journal rapidly into a leading position worldwide for reporting the results of basic research on heart and blood vessels. His editorials were widely quoted, and authors accepted with gratitude the conscientious reviews and criticisms that their papers received from him and his carefully chosen editorial board members. Among his duties as a physiologist, Wiggers also included travel to learn firsthand of outstanding work elsewhere, com- bined with lecturing to review for others recent advances in ongoing research. During his thirty-five years in Cleveland, he made several trips abroad to attend and address congresses and symposia, with visits to laboratories added. In 1939 he was invited to lecture in Argentina and elsewhere in South America. For this he prepared by learning Spanish. Other invitations to give honorary lectures took him to Germany, Holland, England, and from coast to coast in the United States. Because Wiggers had many interests in both physiology and medicine, his mem- berships in scientific societies included a number in each cate- gory, with service as officer in many. His earliest and longest loyalty went to the American Physiological Society, where, in annual meetings for fifty years, he was a dependable source of lively discussion and admonitions to young and old investigators, delivered over his ever-present cigar and with a friendly humor to temper any incisive criticism. He served the Society as Sec- retary, Treasurer, and in 1949 as President. His other member- ships ranged from the American Society of Pharmacology and Experimental Therapeutics to the American College of Physi- cians, American Medical Association, American Heart Asso- ciation (Vice-President, 1947), and numerous cardiology groups, ranging from a local Cleveland area heart society (President, 1955-1956) to the Inter-American Cardiological Society (Presi- dent, 1956~. Honors came to Carl Wiggers in abundance both in early
CARL J OHN WIGGERS 379 life and later, both at home and abroad. The gratitude and homage of his many students and co-workers led to frequent "Anniversary Dinners" in his honor. These included annual gatherings during meetings of the American Physiological So- ciety and special testimonial dinners in Cleveland celebrating his twentieth and twenty-fifth years there and his emeritus year, when his portrait was presented to Western Reserve Medical School. The Circulation Group of the American Physiological Society grants annually to an outstanding physiologist its "Carl I. Wiggers Award and Lectureship." In 1951 an issue of the journal Circulation was dedicated to him. In 1958 a group of his former pupils volunteered research papers that made up an entire number of Circulation Research to commemorate two events: first, the "retirement of Carl J. Wiggers after his five years of devoted service as its first editor," and second, "the seventy-fifth birthday of this man, one of the surviving giants of the legendary age of American physiology." Wiggers received honorary doctorates from his alma mater, the University of Michigan (1951~; the Royal Ludwig-Maxi- milian University of Munich, Germany (1952~; Free University of Brussels, Belgium (1956~; and Ohio State University (1958~. Honorary memberships in academies, professional societies, and university faculties began at home with the Cleveland Academy of Medicine and included honors from many others in the United States, England, Mexico, and several countries in South America. From the American Heart Association he received the Gold Heart Award (1952) and the Albert Lasker Award (1955~. In both he was named "Dean of Cardiovascular Physiologists." Die Deutsche Gesellschaft fur Kreislaufforschung awarded him their Carl Ludwig Medal (1954) and the Royal Academy of Medicine in Belgium awarded him their gold medal (1956~. Carl John Wiggers died suddenly at his home in Cleveland on April 29, 1963, one month short of his eightieth year. His death meant the loss of still another of that small group of
380 BIOGRAPHICAL MEMOIRS brilliant leaders in research who initiated and shaped the rapid growth of physiology in the United States during the first half of this century. Not lost at all, but persisting unchanged, is the lasting heritage of his example, bestowed on everyone who had the privilege of associating with him. To quote from only one of many paragraphs of eulogy and gratitude: "Author, pioneer research worker in cardiovascular physiology, his monument is the host of great students sent into the world imbued with his own philosophy and the values of precision, promptness, hard work and thoroughness. All over the world his work will con- tinue in many other leading physiologists and physicians." WISH to express my special gratitude to Dr. Robert M. Berne for providing the following bibliography prepared from departmental records at Western Reserve University.
CARL JOHN WIGGERS BIBLIOGRAPHY 381 KEY TO ABBREFIA TIONS Alumni Bull. Sch. Med. Affil. Hosp. = Alumni Bulletin of the School of Medicine and Affiliated Hospitals, Western Reserve University Am. Heart I. = American Heart Journal Am. l. NIed. Sci. = American journal of Medical Sciences Am. I. Physiol. = American journal of Physiology Ann. Intern. Med. = Annals of Internal Medicine Annul Rev. Physiol. = Annual Review of Physiology Arch. Intern. Med. = Archives of Internal Medicine Circ. Res. = Circulation Research Exp. Med. Surg. = Experimental Medicine and Surgery Fed. Proc. Am. Soc. Exp. Biol. = Federation Proceedings of the American Society for Experimental Biology i. Am. Med. Assoc. = Journal of the American Medical Association I. Exp. Med. = journal of Experimental Medicine I. Lab. Clin. Med. = Journal of Laboratory and Clinical Medicine I. Phannacol. Exp. Ther. = Journal of Pharmacology and Experimental Therapeutics Physiol. Rev. = Physiological Reviews Proc. Soc. Exp. Biol. Med. = Proceedings of the Society for Experimental Biology and Medicine West. Reserve Univ. Sch. Med. Clin. Bull. = Western Reserve University School of Medicine Clinical Bulletin 19~05 Action of adrenalin on the cerebral vessels. Am. l. Physiol., 14:452- 65. 1907 The innervation of the cerebral vessels as indicated by the action of drugs. Am. I. Physiol., 20:206-33. 1908 Some vasomotor changes in the cerebral vessels obtained by stimu- lating the carotid plexuses. Am. I. Physiol., 21:454-59. 1909 An improved outflow-recording apparatus. Am. i. Physiol., 23:23-27. The innervation of the coronary vessels. Am. i. Physiol., 24:391-405. Studies on inaccessible internal hemorrhages. I. The effect of adrena- lin on intestinal hemorrhage. Arch. Intern. Med., 3:139 58.
382 BIOGRAPHICAL MEMOIRS Studies on inaccessible internal hemorrhages. II. The ineffectiveness of adrenalin in pulmonary hemorrhage. Arch. Intern. Med., 3: 360-67. Action of adrenalin on the pulmonary vessels. l. Pharmacol. Exp. Ther., 1:341-48. - 1910 Prognostic significance of pulse pressure changes during hemorrhage. Arch. Intern. Med., 6:281-9~2. Comparative value of vasomotor drugs in renal hemorrhages. Arch. Intern. Med., 5: 348-60. 1911 The physiology of the pituitary gland and the action of its extracts. Am. I. Med. Sci., 141 :502-15. A physiological investigation of the treatment in hemoptysis. Arch. Intern. Med., 8: 17-38. The modifying influence of anemia on the actions of some well- known drugs. I. Pharmacol. Exp. Ther., 2:39~5 - 96. 1912 Studies on the pulmonary circulation. I. The pressure variations in the pulmonary circulation of the dog studied by a new pulse pressure instrument. Am. I. Physiol., 30:233-57. With K. C. Eberly and H. J. Wenner. Pressor influence of augmented breathing. J. Exp. Med., 15: 174-200. 1913 With E. F. DuBois. Methods for the production of temporary valvular lesions. Proc. Soc. Exp. Biol. Med., 10:87 - 88. The pressure changes in the right ventricle studied by optically re- cording manometers. Proc. Soc. Exp. Biol. Med., 11: 11-12. 1914 The contour of the pressure curve in the pulmonary artery. Am. J. Physiol., 33: 1-12. Observations on the "effective" pressure in the right and left auricles. Am. J. Physiol., 33: 13-24.
CARL JOHN WIGGERS 383 Some factors controlling the shape of the pressure curve in the right ventricle. Am. i. Physiol., 33:382-96. The nature and causes of the respiratory pressure variations in the pulmonary artery. Am. J. Physiol., 35: 124-42. Pathologic physiology of the circulation during hemorrhage. Arch. Intern. Med., 14: 33~7. Further observations on the constricting actions of adrenaline on the cerebral vessels. Journal of Physiology (London), 48:109-12. The respiratory and cardiac variations of intrathoracic pressure and their significance in cardiac contraction. Proc. Soc. Exp. Biol. Med., 11:53-54. The influence of the diaphragm descent on the movements of the heart. Proc. Soc. Exp. Biol. Med., 11: 107-8. Reflex vasodilation is not the cause of the collapsing pulse of aortic insufficiency. Proc. Soc. Exp. Biol. Med., 12:55-56. A Brief Text of Physiology. Ann Arbor: George Wahr Publishing Co. 1915 Modern Aspects of the Circulation in Health and Disease. 1st ed. Philadelphia: Lea & Febiger. 376 pp. Studies on the pathological physiology of the heart. I. The intra- auricular, intraventricular and aortic pressure curves in auricular fibrillations. Arch. Intern. Med., 1 b: 77-9 1. Studies on the pathological physiology of the heart. II. The dynam- ics of aortic insufficiency. Arch Intern. Med., 16: 132-48. An adaptation of Frank's segment capsules for clinical use. l. Am. Med. Assoc., 64: 1305-6. The contour of the normal arterial pulse. l. Am. Med. Assoc., 64: 1380-82. The supraclavicular venous pulse in man. l. Am. Med. Assoc., 64: 1485-87. 1916 The auricular myogram and auricular systole. Am. l. Physiol., 40: 218-29. The influence of the vagus nerves on the fractionate contraction of the right auricle. Am. i. Physiol., 42: 133-40. The time relations of auricular systole. Am. J. Physiol., 42:141-50.
384 BIOGRAPHICAL MEMOIRS 1917 With A. L. Dean, in The principles and practice of registering heart sounds by direct method. Am. l. Med. Sci., 153:666-78. With A. L. Dean, in The nature and time relations of the funda- mental heart sounds. Am. l. Physiol., 42:476-97. The electrocardiogram: its relation to cardiodynamic events. Arch. Intern. Med., 20:93-102. With W. L. Niles. The details of the photographically recorded venous pulse in auricular fibrillation. i. Exp. Med., 25:1-19. With W. L. Niles. The significance of the diastolic waves of the ve- nous pulse in auricular fibrillation. l. Exp. Med., 25:21-32. Fat embolism and shock. Proc. Soc. Exp. Biol. Med., 15:34-36. 1918 Initial and progressive stages of circulatory failure in abdominal shock. Am. i. Physiol., 45:485-99. Shock and circulatory failure, following trauma. Am. l. Physiol., 46:314-28. The clinical registration of cardiac murmurs by the direct method. Arch. Intern. Med., 22:28~0. Circulatory failure: the differentiation between that due to shock and that due to other causes. J. Am. Med. Assoc., 70:508-11. 1919 Factors determining the relative intensities of the heart sounds in different auscultation areas. Arch. Intern. Med., 24:471-96. With H. D. Clough. A physiological investigation into the dynamic action of the heart in functional cardiac disorders. l. Lab. Clin. Med., 4:624-29. 19~20 With L. N. Katz. The specific influence of the accelerator nerves on the duration of ventricular systole. Am. J. Physiol., 53:49-64. With L. N. Katz. The selective effect of the accelerator nerves on ventricular systole. Proc. Soc. Exp. Biol. Med., 17:94-97. The normal and pathologic physiology of the circulation. In: Nel- son's Loose-Leaf Living Medicine, vol. 4, p. 243. New York: Thomas Nelson and Sons.
CARL J OHN WIGGERS 1921 385 Studies on the consecutive phases of the cardiac cycle. I. The dura- tion of the consecutive phases of the cardiac cycle and the criteria for their precise determination. Am. l. Physiol., 56:415-38. Studies on the consecutive phases of the cardiac cycle. II. The laws governing the relative durations of ventricular systole and dias- tole. Am..~. Physiol., 56:439-59. The present status of cardiodynamic studies on normal and patho- logic hearts. (Harvey Lecture) Arch. Intern. Med., 27:475-502. The regulation of the pulmonary circulation. Physiol. Rev., 1:239- 68. The influence of venous return and arterial resistance on the pres- sures within the right and left ventricles. Proc. Soc. Exp. Biol. Med., 18: 144 46. 1922 With L. N. Katz. The contour of the ventricular volume curves under different conditions. Am. l. Physiol., 58:439-75. With W. R. Baker. A radial transmission sphygmograph with rigid support. Am. J. Physiol., 59:454-55. The physiology of the mammalian auricle. IV. The nature of mus- cular contraction in auricular fibrillation and flutter. Am. l. Physiol., 62:310-29. With H. Fell. The cardio-dynamics of mitral insufficiency. Heart, 9: 149-84. 1923 Modern Aspects of the Circulation in Health and Disease. Ed ed. Philadelphia: Lea & Febiger. 662 pp. The cardiodynamics of premature ventricular contractions in the dog. Quarterly Journal of Experimental Physiology, Suppl., pp. 237-38. With W. R. Baker. A new universal optical manometer. l. Lab. Clin. Med., 10: 54-56. 1924 Physiology of circulation. In: Pediatrics, ed. by Isaac A. Abt, vol. 4, pp. 198237. Philadelphia: W. B. Saunders Co.
386 BIOGRAPHICAL MEMOIRS 1925 The independence of electrical and mechanical reactions in the mammalian heart. Am. Heart l., 1: 173-90. With D. l. Edwards. An acid stimulator signal. Am. I. Physiol., 72: 187-88. The fundamental nature of premature ventricular contractions in the dog. Am. J. Physiol., 72: 188-89. With S. R. Burlage. A segment respirometer for studying the effects of CO2 in man. Am. J. Physiol., 72: 192-93. A photokymograph for students. Am. i. Physiol., 72:193-94. The muscular reactions of the mammalian ventricles to artificial surface stimuli. Am. i. Physiol., 73:346-78. Western Reserve University School of Medicine, Department of Physiology. In: Methods and Problems of Medical Education, 3d ser., p. 47. New York: Rockefeller Foundation. 1926 With M. G. Banus. A. On the independence of electrical and me- chanical activity in the mammalian ventricle. B. On the effects of pH changes on conduction in the heart. Am. i. Physiol., 76: 215-16. The fractionate nature of ventricular contraction and the influence of changes in ventricular conduction on the form of the pressure curve. Skandinavisches Archiv fur Physiologie, 49:247-48. 1927 The interpretation of the intraventricular pressure curve on the basis of rapidly summated fractionate contractions. Am. l. Physiol., 80: 1-11. Are ventricular conduction changes of importance in the dynamics of ventricular contractions? Am. I. Physiol., 80:12-30. With L. N. Katz. The influence of high systemic blood pressures on the right ventricle and pulmonary circuit. Am. J. Physiol., 82: 91-98. The dynamics of ventricular alternation. Annals of Clinical Medi- cine, 5: 1022-27. Studies on the cardiodynamic actions of drugs. I. The applications
CARL JOHN WIGGERS 387 of optical methods of pressure registration in the study of cardiac stimulants and depressants. i. Pharmacol. Exp. Ther., 30:217 - 31. Studies on the cardiodynamic actions of drugs. II. The mechanism of cardiac stimulation by epinephrine. l. Pharmacol. Exp. Ther., 30:233 - 50. With B. Stimson. Studies on the cardiodynamic actions of drugs. III. The mechanism of cardiac stimulation by digitalis and g-stro- phanthin. I. Pharmacol. Exp. Ther., 30:251-69. The cause of temporary ventricular alternation following a long diastolic pause. In: Contributions to Medical Science, dedicated to Aldred Scott Warthin, ed. by Willard l. Stone, p. 65. Ann Arbor: George Wahr. Also in Proc. Soc. Exp. Biol. Med., 24: 386-87. 1928 With L. N. Katz. The static and dynamic effort of the heart during ejection. Am. l. Physiol., 85:229-50. The harmonic analysis of intraventricular pressure curves. Am. I. Physiol., 86: 435-49. The interrelations of physiology and internal medicine. l. Am. Med. Assoc., 91: 270-74. I. Laboratory and clinical methods of studying the heart beat. II. The physiologic basis for the clinical interpretation of cardiac irregularities. III. The physiologic principles underlying the adaptation of the heart. Northwest Medicine, 27:466-68. Pressure Pulses in the Cardiovascular System. New York: Longmans, Green. 200 pp. 1929 With M. L. Siegel. The importance of the variable capacity of the aorta in averting "back pressure" in the right heart and pul- monary artery. Am. i. Physiol., 89:417-27. With M. G. Banus. The effects of CO2 and fixed-acid acidosis on conduction in the mammalian heart. Am. l. Physiol., 90:218-29. A study of the direct effect of hypercapnia on the contraction of the mammalian ventricle. Am. l. Physiol., 90:230-41. Die pathologische physiologic des Kreislaufs bei Klappenerkrankun- gen des Herzens. Ergebnisse der Physiologie, 29:250-369. The value and limitations of laboratory methods in clinical investi-
388 BIOGRAPHICAL MEMOIRS gation of cardiovascular diseases. New Orleans Medical and Sur- gical Journal, 81:601~. Principles and Practice of Electrocard iography. St. Louis: C. V. Mosby Co. 226 pp. 1930 Monophasic and deformed ventricular complexes resulting from surface application of potassium salts. Am. Heart l., 5:346-50. Studies of ventricular fibrillation caused by electric shock. II. Cine- matographic and electrocardiographic observations of the nat- ural process in the dog's heart. Its inhibition by potassium and the revival of coordinated beats by calcium. Am. Heart i., 5:351- 65. Studies of ventricular fibrillation caused by electric shock. I. The revival of the heart from ventricular fibrillation by successive use of potassium and calcium salts. Am. i. Physiol., 92:223-39. Studies of ventricular fibrillation caused by electric shock. III. The action of antagonistic salts. Am. l. Physiol., 93:197212. Physiologic meaning of common clinical signs and symptoms in cardiovascular disease. I. Am. Med. Assoc., 96:603-10. With H. Theisen and H. A. Williams. Further observations on experimental aortic insufficiency. II. Cinematographic studies of changes in ventricular size and in left ventricular discharge. Journal of Clinical Investigation, 9:215-33. The adsorptions of drugs from the right ventricular cavity. l. Pharmacol. Exp. Ther., 39:209 - 19. With H. Green. Experimental aortic insufficiency. I. Regurgitation maximum and mechanisms for its accommodation within the mammalian ventricle. Proc. Soc. Exp. Biol. Med., 27:599-603. Further observations on experimental aortic insufficiency. III. Fac- tors accountable for the systolic collapse of the central pressure pulse. Proc. Soc. Exp. Biol. Med., 28:85-88. 1931 With A. B. Maltby. Further observations on experimental aortic insufficiency. IV. Hemodynamic factors determining the charac- teristic changes in aortic and ventricular pressure pulses. Am. J. Physiol., 97: 689-705. The magnitude of regurgitation with aortic leaks of different sizes. J. Am. Med Assoc., 97:1359-64.
CARL JOHN WIGGERS 389 1932 With A. B. Maltby. Studies on human blood pressure criteria and methods. I. The effects of partial and complete occlusion on actual pressures in compressed arteries. Am. l. Physiol., 100: 604-13. With O. Orias. The circulatory changes during hyperthermia pro- duced by short radio waves (radiothermia>. Am. J. Physiol., 100: 614-28. Physical and physiological aspects of arteriosclerosis and hyperten- sion. Ann. Intern. Med., 6: 12-30. 1933 Anatomy and physiology. In: White House Conference on Child Health and Protection. Growth and Development of the Child. Part II. Anatomy and Physiology, pp. 288-332. New York: Cen- tury Company. With F. D. McCrea. Rhythmic arterial expansion as a factor in the control of heart rate. Am. l. Physiol., 103:417-31. With D. E. Gregg. The circulatory effects of acute experimental hypervolemia. Am. I. Physiol., 104:423-32. With F. S. Cotton. Studies on the coronary circulation. I. The coro- nary pressure pulses and their interpretation. Am. I. Physiol., 106:9-15. With F. S. Cotton. Studies on the coronary circulation. II. The sys- tolic and diastolic flow through the coronary vessels. Am. I. Physiol., 106:597-610. 1934 The dominant control of mammalian ventricular dynamics by ini- tial length. Revista de la Sociedad Argentina de Biologia, Suppl., 10:546. Further observations on systolic and diastolic coronary flow under natural conditions. Science, 80:545-46. Physiology in Health and Disease. 1st ed. Philadelphia: Lea & Febiger. 1156 pp. 1935 With R. Tennant. The effect of coronary occlusion on myocardial contraction. Am. l. Physiol., 112:351-61.
390 BIOGRAPHICAL MEMOIRS With D. E. Gregg and H. D. Green. Phasic variations in peripheral coronary resistance and their determinants. Am. i. Physiol., 112:362-73. With H. D. Gregg and D. E. Gregg. The phasic changes in coronary flow established by differential pressure curves. Am. l. Physiol., 112:627-39. With H. C. Wiggers. The interpretation of monophasic action po- tentials from the mammalian ventricle indicated by changes following coronary occlusion. Am. J. Physiol., 113:683-89. 1936 With M. H. Fineberg. Compensation and failure of the right ventri- cle. Am. Heart l., 11 :255-63. With H. D. Green. The ineffectiveness of drugs upon collateral flow after experimental coronary occlusion in dogs. Am. Heart i., 11:527-41. The inadequacy of the normal collateral coronary circulation and the dynamic factors concerned in its development during slow coronary occlusion. Am. Heart I., 11 :641~7. Cardiac massage and countershock in revival of the mammalian ven- tricles from fibrillation due to coronary occlusion. Am. l. Phys- iol., 116: 161-62. With i. R. Johnson. The alleged validity of coronary sinus outflow as a criterion of coronary reactions. Am. J. Physiol., 118:38-51. With H. D. Green. Ineffectiveness of drugs upon collateral coronary flow. Proc. Soc. Exp. Biol. Med., 33:578-79. The physiology of the coronary circulation. In: Diseases of the Coro- nary Arteries and Cardiac Pain, ed. by R. L. Levy, p. 57. New York: Macmillan Publishing Co., Inc. 1937 The influence of Western Reserve University Medical School in China. Clinical Bulletin of the University Hospitals of Cleveland, 1:12. Physiology in Health and Disease. 2d ed. Philadelphia: Lea & Febiger. 1124pp. 1938 Aspectos fisiologicos de la hipertension arterial. Actas y Trabajos, Sexto Congreso Nacional de Medicine, Cordoba, Oct., p. 238.
CARL J OHN WIGGERS 391 The dynamics of hypertension. Am. Heart i., 16:515~3. The influence of vascular factors on mean pressure, pulse pressure and phasic peripheral flow. Am. J. Physiol., 123:64~58. With R. Wegria. Active changes in size and distensibility of the aorta during acute hypertension. Am. l. Physiol., 124: 603-11. Fibrillacion ventricular y resusitacion. Boletin Academia Nacional de Medicina, Buenos Aires, 119: 567-87. A note on some old experiments upon the cerebral circulation with present day application. Libro de Oro, Buenos Aires, 3:1487. 1939 With G. W. Wright and W. R. Hallaran. The economy of effort in- dex for hearts of normal and hypertensive subjects. Am. l. Physiol., 126:89-96. Inter-relaciones entre fisiologia y medicine. Revista Medica de Cor- doba, 27: 1709. Physiology in Health and Disease. ad ed. Philadelphia: Lea 8c Febiger. 1144 pp. 1940 With N. H. Boyer and R. W. Eckstein. The characteristics of normal heart sounds recorded by direct methods. Am. Heart J., 19:257- 74. The mechanism and nature of ventricular fibrillation. Am. Heart l., 20:399-412. The physiologic basis for cardiac resuscitation from ventricular fibrillation method for serial defibrillation. Am. Heart I., 20: 413-22. With R. Wegria. Ventricular fibrillation due to single, localized induction and condenser shocks applied during the vulnerable phase of ventricular systole. Am. J. Physiol., 128:500-505. With E. W. Shannon. The dynamics of the frog and turtle hearts- the non-refractory phase of systole. Am. J. Physiol., 128:709-15. With l. T. Dingle, G. T. Kent, and L. L. Williams. A study of alleged quantitative criteria of vasomotor action. Am. I. Physiol., 130:63-68. With R. Wegria. Factors determining the production of ventricular fibrillation by direct currents (with a note on chronaxie). Am. J. Physiol., 131: 10~18.
392 BIOGRAPHICAL MEMOIRS With R. Wegria. Production of ventricular fibrillation by alternat- ing currents. Am. i. Physiol., 1 3 1: 1 1 9-28. With R. Wegria. Quantitative measurement of the fibrillation thresholds of the mammalian ventricles with observations on the effect of procaine. Am. J. Physiol., 131:296-308. With R. Wegria and B. Pinera. The effects of myocardial ischemia on the fibrillation threshold the mechanism of spontaneous ventricular fibrillation following coronary occlusion. Am. l. Physiol., 131:309-16. With M. L. Ford, C. L. Petersilge, and A. F. Young. Effect of acute anoxia on the economy of effort index in man. Proc. Soc. Exp. Biol. Med., 45: 353-55. With P. Dow. Limitations of myocardial recovery from fibrillation through countershock. Proc. Soc. Exp. Biol. Med., 45:355-57. Pathways of medical progress. Science, 91:25-31. 1941 The ineffectiveness of vagal stimulation on ventricular fibrillation in dogs. Am. J. Physiol., 133:634-36. With R. Wegria and G. K. Moe. Comparison of the vulnerable periods and fibrillation thresholds of normal and idioventricular beats. Am. l. Physiol., 133:651-57. With G. K. Moe and A. S. Harris. Analysis of the initiation of fibrillation by electrographic studies. Am. J. Physiol., 134:473-92. Cardiac adaptations in acute progressive anoxia. Ann. Intern. Med., 14: 1237~7. The mechanisms of peripheral circulatory failure. Ann. Intern. Med.,15:178-89. With H. D. Green. Heart. Ann. Rev. Physiol., 3:313-42. Applicability of experimental results to the shock problem in man. J. Am. Med. Assoc., 117:1143-47. 1942 With J. M. Werle and R. S. Cosby. Observations on hemorrhagic hypotension and hemorrhagic shock. Am. J. Physiol., 136:401-20. With J. M. Werle and P. C. Shea. Cardiac and peripheral resistance factors as determinants of circulatory failure in hemorrhagic shock. Am. J. Physiol., 136:421-32.
CARL JOHN WIGGERS 393 With R. N. Lewis and I. M. Werle. The behavior of the spleen in hemorrhagic hypotension and shock. Am. l. Physiol., 138:205-11. Basic hemodynamic principles essential to interpretation of cardio- vascular disorders. Bulletin of the New York Academy of Medi- cine, 18:3-17. Aviation physiology. I. The effects of anoxia. West. Reserve Univ. Sch. Med. Clin. Bull., 6:82-87. With I. M. Werle. Observations on hemorrhagic shock. Fed. Proc. Am.Soc.Exp.Biol., 1:91. With I. M. Werle and P. C. Shea. Cardiac and peripheral determi- nants of hemorrhagic shock. Fed. Proc. Am. Soc. Exp. Biol., 1:92. The present status of the shock problem. Physiol. Rev., 22:74-123. With I. M. Werle. Exploration of a method for standardizing hemor- rhagic shock. Proc. Soc. Exp. Biol. Med., 49:604-6. 1943 With R. Wegria and A. G. Rojas. A study of spontaneous fulminant shock in a heart-lung dog preparation. Am. J. Physiol., 138:212- 29. With R. Wegria and N. D. Nickerson. Reactions of the aorta in hemorrhagic hypotension and shock. Am. I. Physiol., 138:491-94. With S. Middleton. Some effects of pectin solutions during post- hemorrhagic hypotension. Am. l. Physiol., 140:326-33. Recent studies on the irreversibility characteristic of shock. Exp. Med. Surg., 1 :2-13. With K. A. Huizenga and B. L. Brofman. The ineffectiveness of adrenal cortex extracts in standardized hemorrhagic shock. l. Pharmacol. Exp. Ther., 78:139-53. With K. A. Huizenga and B. L. Brofman. Ineffectiveness of adreno- cortical preparations in standardized hemorrhagic shock. Proc. Soc. Exp. Biol. Med., 52:77. Recent observations on the value of adrenal cortex preparations in hemorrhagic shock. University Hospital Bulletin, University of Michigan, 9:61. 1944 With S. Middleton. The effects of renin and angiotonin on cardiac output and total peripheral resistance. Am. J. Physiol., 141:128- 31.
394 BIOGRAPHICAL MEMOIRS Laboratory studies of clinical problems in cardiology. Archivos del Instituto de Cardiologia de Mexico, 14:3-8. Cardiovascular aspects of shock and transfusion. Chicago Heart Association Bulletin, 22~1-6~: 1-~. Torald Sollman The Professor and Dean. West. Reserve Univ. Sch. Med. Clin. Bull., 8:82 - 84. Correlations of physiology instruction with war problems. Journal of the Association of American Medical Colleges, 19:151-58. Sequencia das reacoes cardiovasculares no choque. Rosenha Clinico- Cientifica, 13: 144-49. Physiology in Health and Disease. 4th ed. Philadelphia: Lea & Febiger. 1174 pp. 1945 Failure of transfusion in irreversible hemorrhagic shock. Am. l. Physiol., 144:91-101. The functional consequences of coronary occlusion. Ann. Intern. Med., 23: 158-69. 1946 With D. F. Opdyke and I. R. Johnson. Portal pressure gradients under experimental conditions including hemorrhagic shock. Am. l. Physiol., 146: 192-206. With D. F. Opdyke. Studies of right and left ventricular activity during hemorrhagic hypotension and shock. Am. l. Physiol., 147:270-80. With R. W. Eckstein and I. M. Liebow. Limb blood flow and vascular resistance changes in dogs during hemorrhagic hypo- tension and shock. Am. J. Physiol., 147:685-94. 1947 La similitude de l'insu~sance circulatoire dans le choc aver volume sanguin diminue ou normal. Acta Cardiologica, 2:113-35. Myocardial depression in shock. Am. Heart l., 33:633-50. With R. W. Eckstein and G. R. Graham. Phasic changes in inferior cave flow of intravascular origin. Am. J. Physiol., 148:740-44. With R. W. Eckstein, G. R. Graham, and I. M. Liebow. Comparison
CARL JOHN WIGGERS 395 of changes in inferior cave flow after hemorrhage and circulatory failure following transfusion. Am. l. Physiol. 148:74553. With M. N. Levy and G. R. Graham. Regional intrathoracic pres- sures and their bearing on calculation of effective venous pres- sures. Am. i. Physiol., 151: 1-12. With R. M. Kohrman and l. B. Nolasco. Types of afferent fibers in the phrenic nerve. Am. I. Physiol., 1 5 1: 547-53. Peripheral circulation. Annul Rev. Physiol., 9:255-300. With D. T. Overbey, A. Ramirez, and H. C. Lawson. Bleeding vol- ume and blood volume in hemorrhagic shock. Federation Pro- ceedings, 6: 173-74. 1948 With R. S. Post and P. H. Visscher. Sequential changes in oxygen consumption during oligemic and normovolemic shock and their meaning. Am. i. Physiol., 153:71-80. With l. L. Duomarco and W. H. Dillon. Comparison of cardiac output by a direct method and the Hamilton-Remington proce- dure. Am. i. Physiol., 154: 290-96. 1949 The Department of Physiology. Alumni Bull. Sch. Med. Affil. Hosp., 13:19. Cardiological principles in surgery. Arquivos Brasileiros de Cardio- logia, 2:239-52. The interpretation and treatment of heart failure during anesthesia and operations. Ohio State Medical Journal, 45:1169-75. Fisiologia normal y Patologica, 1st ed. Madrid: Espase-Calpe. Physiology in Health and Disease. Sth ed. Philadelphia: Lea 8c Febiger. 1242 pp. 1950 Human experimentation as exemplified by the career of Dr. William Beaumont. Alumni Bull. Sch. Med. Affil. Hosp., 14:60. The problem of functional coronary collaterals. Exp. Med. Surg., 8:402-21. Physiology of Shock. New York: The Commonwealth Fund; Cam- bridge, Mass.: Harvard Univ. Press. 459 pp.
396 BIOGRAPHICAL MEMOIRS 19~51 Prefatory chapter. Physiology from 1900 to 1920: incidents, acci- dents, and advances. Annul Rev. Physiol., 13: 1-20. With T. C. Gupta. Basic hemodynamic changes produced by aortic coarctation of different degrees. Circulation, 3:17-31. Determinants of cardiac performance. Circulation, 4:485-95. With i. Bordley, III, C. A. R. Conner, W. F. Hamilton, and W. l. Kerr. Recommendations for human blood pressure determina- tions by sphygmomanometers. Circulation, 4: 503-9. 1952 Dynamics of ventricular contraction under abnormal conditions. (The Henry Jackson Memorial Lecture) Circulation, 5:321 - 48. The functional importance of coronary collaterals. Circulation, 5: 609-15. Circulatory Dynamics: Physiological Studies. New York: Grune & Stratton. 107 pp. 1953 With R. S. Alexander. Cardiac factors of safety. Editorial. Circ. Res., 1 :99-101. With H. M. Geller and M. Brandfonbrener. The derivation of coro- nary sinus flow during elevation of right ventricular pressure. Circ.Res.,1:152 - 56. Defibrillation of the ventricles. Editorial. Circ. Res., 1:191-99. With A. Hurlimann. The effects of progressive general anoxia on the pulmonary circulation. Circ. Res., 1:230-37. 1954 The interplay of coronary vascular resistance and myocardial com- pression in regulating coronary flow. Circ. Res., 2:271-79. Research by groups and individuals. Editorial. Circ. Res., 2:479-82. Function of the right ventricle. Science, 120: 789-90. Spezielle hamodynamische Gesichtspunkte experimenteller Herz- klappenfehler. Verhandlungen der Deutschen Gesellschaft fur Kreislaufforschung, 19~:3-19. Fisiologia Normal y Patologica. Cd ed. Madrid: Espasa-Calpe.
CARL J OHN WIGGERS 397 1956 Some special aspects of hemodynamics. Bulletin de l'Academie Roy- ale de Medecine de Belgique, 21:261-83. Dynamic reactions induced by compression of an artery. Circ. Res., 4:4-7. lg58 Reminiscences and Adventures in Circulation Research. New York, London: Grune & Stratton. 404 pp.
