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Acute coronary occlusion always results in deathor does it?The observations of William T. Porter

W. BRUCE FYE, M.D.

FREDRICK WILLIUS, a physician and historian ofcardiology, claimed in 1945, "The achievement ofscientific progress is irrevocably based on past experi-ences, not alone on the experience of one generation ofscientists but rather on the numerous generationswhich have been predecessors. " ' The recent introduc-tion of thrombolytic therapy with intracoronary strep-tokinase for acute coronary occlusion has stimulatedrenewed interest in the consequences of acute obstruc-tion of the coronary arteries.`> Although Pierre Chiracobserved the effects of experimental ligation of thecoronary arteries in a dog in 1698, there was littleinterest in this subject until the closing years of the19th century.5 In 1893, William T. Porter, a youngAmerican physiologist, reported that experimentalcoronary occlusion in the dog was not always fatal.This observation contradicted the results of other in-vestigators who claimed that ligation of the coronaryarteries was followed by cardiac arrest in virtually allinstances. The scope and sophistication of Porter'sexperiments on acute coronary occlusion, performednearly a century ago, will surely surprise present dayclinicians and investigators in the field. His thoroughstudies of the effects of acute coronary obstruction inexperimental animals ultimately had a significant im-pact on clinical medicine. James B. Herrick's recogni-tion of the clinical syndrome of acute myocardial in-farction with survival in man can be traced, in part, toPorter's observations.

Porter was born in Plymouth, Ohio, in 1862.6 7 Theson of a physician, he entered St. Louis Medical Col-lege in 1882. The year Porter matriculated the curricu-

Dr. Fye is the Chairman of the Department of Cardiology at theMarshfield Clinic in Marshfield, Wisconsin, a Clinical Assistant Pro-fessor of Medicine at the University of Wisconsin in Madison and at theMedical College of Wisconsin in Milwaukee, and a member of severalsocieties, including the American Osler Society and the American Asso-ciation for the History of Medicine. He has had a long-standing interestin the literature and history of medicine, the history of cardiology, andthe development and implementation of advances in diagnostics andtherapeutics, leading to numerous publications in these areas.

Address for correspondence: W. Bruce Fye, M.D., Department ofCardiology, Marshfield Clinic, 1000 North Oak Ave., Marshfield, WI54449.

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lum was extended from two to three years and labora-tory demonstrations and experiments in physiologywere introduced.8 Correspondence that has recentlybecome available provides valuable insight into thegenesis of Porter's interest in experimental physiologyas well as the origin of his experiments on ligation ofthe coronary arteries.9 Porter's interest in physiologycan be traced to Gustav Baumgarten, who had becomeprofessor of physiology at St. Louis Medical Collegein 1873. Baumgarten was born in Germany in 1837and emigrated to St. Louis as an adolescent, where hegraduated from high school and St. Louis MedicalCollege. After graduation, Baumgarten returned to hisnative land for three years of postgraduate training.Although Germany would rapidly eclipse France as theworld center of scientific medicine, Baumgarten wasone of the first American medical graduates to study inGermany.'` As was the case with virtually all Ameri-can medical professors in the 1870s, Baumgarten wasprimarily a medical practitioner who taught physiol-ogy part time. His reputation extended beyond St.Louis, however, and he was invited to be an originalmember of the Association of American Physicianswhen it was founded in 1886 by William Osler andother leading American physicians. Baumgarten at-tended the first meeting of the Association in June1886. Other members present included the Philadel-phia physician-scientists S. Weir Mitchell, WilliamPepper, Horatio C. Wood, and James Tyson, all fromthe University of Pennsylvania. Mitchell was a pio-neering experimental physiologist and a trustee of theUniversity of Pennsylvania. 11 It is likely that Baumgar-ten arranged for his pupil Porter to work in the physiol-ogy laboratory of the University of Pennsylvania. Thehead of the laboratory at this time was Edward T.Reichert, a recent graduate of the University of Penn-sylvania, who studied physiology in Berlin, Leipzig,and Geneva from 1882 to 1885.12

In 1887, at the age of twenty-four, Porter embarkedon a career as a physiologist. Writing to Baumgartenfrom Philadelphia, he exclaimed that he was "begin-

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ning to feel like a physiologist. . . Fortunately I havefull permission to work on my own lines and shall leanon others as little as possible. Experimental physiologyis, it appears to me, very like many other things in thisworld, no amount of seeing other people work willmake you competent to do the work yourself. So myplan is to have Dr. Kemp or Dr. Reichert do the experi-ment once, and after that to be at hand when I get intohot water, which will probably be rather often."13 Atthe University of Pennsylvania, Porter came into con-tact with several individuals who were familiar withmodem techniques of experimental physiology.George Kemp had received a Ph.D. in biology at JohnsHopkins under H. Newell Martin, America's leadingphysiologist. Porter also received encouragement fromthe University's professor of chemistry, John Mar-shall, who advised him "to begin some original re-search immediately upon . . . return to St. L(ouis). " 4

Baumgarten was obviously a major supporter ofPorter's interests in the scientific side of medicine. Atthe 1888 meeting of the Association of American Phy-sicians, Baumgarten presented the results of his clini-cal observations in patients with cardiac arrhythmias. 15At this meeting Baumgarten heard William H. Draper,a New York physician-scientist, deliver his presiden-tial address, "On the Relations of Scientific to Practi-cal Medicine," in which the increasingly commontheme of the need for specialization in science and inpractice was put forth. Only a handful of Americanshad devoted themselves to full-time careers in the basicmedical sciences when Baumgarten heard Draper pro-claim the value of ". . . the independent cultivation ofthe science and the art (of medicine)." d 16 Baumgarten'spupil Porter, while in Philadelphia, declared to hismentor, 'I shall return home with a determination todevote my life, as far as possible, to scientificwork. " 1' Porter recognized the obstacles to a scientificcareer and appealed to Baumgarten,

Will you let me take you into- my confidence in respect to a'scheme' which is very near to my heart? It is nothing more thanthe acquisition of a private laboratory, wherein I can carry onsome original investigations. Now, surely, you will not con-demn me as visionary until you hear all. There are two obsta-cles, 1. Lack of money. 2. Lack of time.. Such is my castlein Spain. I decline to believe it visionary. I am determined thatthis disembodied spirit shall erelong be a thing of flesh andblood, and very much alive. How, indeed, am I to do originalwork without a laboratory? While there are those who do notconsider research to be the chief end of man, I trust that you willconcede it to be a very prominent end.'7

Porter was appointed assistant professor of physiologyupon his return to St. Louis in the fall of 1887; thefollowing year he succeeded his teacher Baumgarten

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as professor of physiology at St. Louis Medical Col-lege.

In the spring of 1889 Porter traveled abroad for a"studienreise" that would take him to a number of theleading medical and scientific institutions in Europe.This period of formal training in experimental physiol-ogy and related sciences was undoubtedly encouragedby Baumgarten and Porter's Philadelphia teachers.Writing on Christmas day, 1889, from the Physiologi-cal Institute in Berlin, Porter informed Baumgarten hewas writing a letter to the president of St. Louis Medi-cal College "containing proposals for an extension ofthe physiological work. . . The object to be gained isthe establishment of a laboratory for advanced work inphysiology, a laboratory in which research work shallbe systemically pursued and encouraged. The plan isentirely practicable and I am sure it can be made topay. Such an aim is as dear to you as to me and I do notfear that you will refuse your active support."'58 Porterviewed the establishment of a program of original re-search at the medical school as a significant componentof the larger movement to elevate the standard of medi-cal education in America. As he witnessed firsthandthe dramatic advances in medicine facilitated by thestructure of the German university system with its em-phasis on original research and specialization, Porter'scommitment to a career as a professional physiologistdeepened. At the beginning of his second year abroadhe wrote to Baumgarten

There can be no question that I can be more useful in St. Louisas a physiologist than as a practitioner. The making of a physio-logical institute in our community is worth living for. It is notpossible to succeed in such an undertaking and to succeed inpractice at the same time. To practice medicine and experimen-tal physiology is to be an amateur in two things. I must make achoice.. . Physiology means absolute poverty for some years,comparative poverty during life. Practice means giving up thebest thing in sight for the sake of material comforts. These arethe horns of the dilemma. I believe that I have chosen wisely.'9

Porter returned to Europe in the summer of 1891. Hewent to the Physiological Institute at the University ofBreslau to investigate the circulation of the brain underthe supervision of Karl Hiirthle, who had recently per-fected a more sensitive manometer for recording intra-vascular pressures. Hiirthle encouraged Porter to initi-ate a series of experiments in which the newlydesigned manometers were used to record intracardiacand intravascular pressures in experimental animals.In these sophisticated experiments Porter simulta-neously recorded aortic and left ventricular pressuresusing a double-lumen catheter that had been passedretrograde into the left ventricle from the carotid ar-tery. Porter, clearly proud of his research, exclaimed

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to Baumgarten, "I am quite happy over my Herzar-beit, for it is timely, and I think interesting. At allevents it is a positive result and is altogether my ownwork. I am glad to be able to show our people some-thing tangible to prove that the policy of allowing meto work here during the summer-semester is a goodone. They would perhaps believe that I had learnedsomething even if I had nothing to show for it, but it isjust as well to have documentary evidence. "20

The results of Porter's hemodynamic experimentswere published in the Journal ofPhysiology in 1892.21Porter returned to Europe in the spring of 1892 andwent to Berlin to resume his studies under JohannesGad, with whom he had worked during his first yearabroad. Gad had been a pupil and associate of many ofthe leaders of German physiology and one of his majorinterests was the circulatory system. The origin of Por-ter's classic experiments on ligation of the coronaryarteries can be traced directly to Gad. Porter explainedto Baumgarten, "The morning after my arrival in Ber-lin, I went to the Physiological Institute where I had avery pleasant welcome. Prof. Gad talked a long timeabout various lines of investigation, and we finallyselected the influence of ligature of the coronary arteryupon the contractions of the heart. "22 Porter outlinedthe specific goals of his proposed experiments andrevealed his expectation that this theme would serve asa focus for continued investigation upon his return toSt. Louis.

The British physician and physiologist MarshallHall had claimed in 1842 that sudden death was theusual result after interruption of the coronary circula-tion. This led John Erichsen, a medical graduate ofUniversity College in London and pupil of the innova-tive surgeon Robert Liston, to undertake a series ofexperiments in dogs and rabbits in which the coronaryarteries were ligated. Erichsen demonstrated that liga-ture of all of the coronary arteries led to irregularitiesof the heart action and cardiac arrest within thirty min-utes.23 Additional experiments on the effects of coro-nary ligation were reported in 1862 by Panum, a pupilof the great German pathologist Rudolph Virchow,and von Bezold in 1867, among others. Julius Cohn-heim, another pupil of Virchow, initiated a series ofexperiments on the effects of coronary ligation in thelate 1 870s. He reported that ligature of any branch ofthe left or right coronary artery in the dog led to suddencardiac standstill, usually within two minutes after oc-clusion.24 On the basis of his experiments, Cohnheimconcluded that the coronary arteries were end arterieswithout functional anastomoses. Cohnheim's observa-tions and conclusions were controversial and this con-

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tributed to Gad's suggestion that Porter pursue this lineof investigation. Referring to the published work onexperimental coronary occlusion, Porter exclaimed,"Seldom have the results of physiological studies beenmore at variance. The attentive reader finds no state-ment that is not denied, no fact not in dispute. Thesecontroversies would alone compel a new examinationof the interesting phenomena in question, and the ne-cessity of further research is increased by the knowl-edge that changes in intracardiac pressure followingclosure of the coronary arteries have been inferredrather than determined, and have never been studiedwith the improved methods of the present day."25

Porter's experiments on ligation of the coronaryarteries were begun in May 1892 at the University ofBerlin and continued in St. Louis the following year.St. Louis Medical College had become the MedicalDepartment of Washington University in 1891, and ayear later a major new building was erected that con-tained "laboratories fully equipped with every modernapparatus adapted for demonstration and for originalresearch work."26 Porter published the results of hiscoronary artery ligation experiments in 1893. This pa-per began with a comprehensive review of the litera-ture, which revealed Porter's thorough knowledge ofthe earlier work on this subject. In his experiments,Porter ligated the right, left anterior descending, cir-cumflex, or septal artery in dogs. The most importantresults related to the effect of ligation on left ventricu-lar function and the incidence of fatal cardiac arrhyth-mias. Among Porter's conclusions were that cardiacstandstill frequently occurred with ligation of the leftanterior descending or circumflex coronary arteries butwas unusual with ligation of the right coronary artery.Unlike Cohnheim, Porter found that both ventriclesstopped beating at essentially the same time in all in-stances. The arrhythmia Porter observed and describedwas ventricular fibrillation and he found it was irre-versible. He also noted the relationship of the frequen-cy of extrasystoles to the likelihood of cardiac arrest.

Using the sophisticated physiologic apparatus hehad brought from Europe, Porter made the first accu-rate measurements of the effects of coronary ligationon intracardiac and intra-aortic pressure. He observedthat ligation was followed almost immediately by agradual but continuous decrease in peak intraventricu-lar pressure. In addition to noting a decline in systolicpressure, Porter observed an increase in left ventriculardiastolic pressure after the onset of ventricular fibrilla-tion. A major conclusion Porter reached was that liga-tion of the coronary arteries was not uniformly fatal.This claim contradicted most other observations and

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served as a stimulus for continued investigation byPorter and others into the effects of sudden coronary

occlusion. Although there was increasing clinical in-terest in the relationship of coronary artery disease tosudden death, it would be more than a decade beforethese observations were used by a clinician (James B.Herrick) to explain certain phenomena observed inmedical practice.27

In separate experiments performed early in 1893,Porter investigated the pathology of myocardial infarc-tions produced by ligature of the left anterior descend-ing coronary artery in the dog. These experiments,performed in St. Louis and subsequently presentedbefore the Physiological Society of Berlin, were un-

dertaken to confirm or refute the existence of a coordi-nating center for ventricular contraction, which hadbeen proposed by the German physiologist HugoKronecker. Porter concluded that such a coordinatingcenter did not exist, and in the course of his experi-ments he described the pathologic changes of the myo-cardium supplied by ligated coronary arteries. Hiswere among the earliest pathologic and histologic de-scriptions of myocardial infarction, which had firstbeen reported by Weigert in 1880.28,29By the time Porter was thirty he had made several

important career decisions. He was determined to be-come a professional physiologist, although the oppor-

tunities for this in America were severely limited. Al-though he pursued a number of research themes,including anthropometry and respiratory physiology,Porter's dominant interest was circulatory physiology,especially the effects of coronary occlusion. It was

becoming increasingly clear to Porter that it would beimpossible for him to devote himself exclusively tophysiology if he remained in St. Louis. Writing toBaumgarten on May 29, 1893, he claimed, "Afternearly a year's careful consideration I have decidedthat it would be inadvisable for me to accept any workin the university which would take me away fromPhysiology, in the traditional sense. The money hasbeen a great temptation, but I am convinced that I mustnot take on any more responsibilities. I wish, as you

know, to be an investigator, not merely a teacher. "30

The forced resignation due to alcoholism of H.Newell Martin from the chair of physiology at JohnsHopkins in April 1893 had major implications for Por-ter's career.31 William Howell, a former pupil andassociate of Martin, was called from Harvard to Balti-more to succeed Martin. This created an opening inHenry Bowditch's physiology department at Harvard.It is not surprising that Porter was selected to fill thisposition; he shared Bowditch's interests in circulatory

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physiology and anthropometry, had sophisticated post-graduate training in modem experimental physiologyin Germany, and had demonstrated productivity inoriginal research.32 Few Americans could claim theexpertise in experimental physiology that Porter pos-sessed by 1893. Bowditch and other physiologists hadheard the results of Porter's research on ligation of thecoronary arteries at the fifth annual meeting of theAmerican Physiological Society in December 1892.Porter was elected assistant professor of physiology atHarvard Medical School on October 30, 1893, andmoved to Boston before Christmas.

Porter's appointment at the Harvard Medical Schoolallowed him to devote himself exclusively to physiol-ogy. Moreover, several members of the Harvard facul-ty shared his interest in the pathophysiology of thecirculatory system. Henry Bowditch had a soundknowledge of cardiovascular physiology, which datedfrom his studies with Carl Ludwig at the Leipzig Phys-iological Institute two decades earlier. George Stew-art, an assistant in Bowditch's laboratory during thefirst year of Porter's Harvard appointment, receivedhis education at Edinburgh University and studiedphysiology at the University of Berlin in 1886. From1889 to 1893 Stewart worked in Michael Foster'sphysiology laboratory at the University of Cambridge,where he investigated the cardiac nerves and the veloc-ity of blood flow.33 Porter undoubtedly received en-couragement for continuing his investigations into thephysiology of the coronary circulation from the newlyelected professor of pathologic anatomy, WilliamCouncilman, who had been a pupil of H. Newell Mar-tin in Baltimore, and subsequently studied pathologywith Cohnheim and Weigert when those German pa-thologists were actively investigating the effects ofcoronary occlusion.27' 34The coronary artery experiments initiated in Ger-

many and continued in St. Louis were resumed inBoston. By 1895 Porter was also studying the effect ofacute anemia on left ventricular function.35 In additionto ligating the coronary arteries, Porter occluded thesevessels by embolization with lycopodium spores anddeveloped an innovative technique for obstructingthem with a solid glass rod inserted through a smallincision in the innominate artery. The tip of the rodwas tapered and curved to facilitate its introductioninto a coronary ostium. The tip of the sound was ad-vanced to the sinuses of Valsalva until resistance wasmet from an aortic valve leaflet. Porter would thenwithdraw the sound slightly and by rotating the tipwould locate the coronary ostium. This remarkabletechnique, performed before the discovery of x-rays,

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preceded clinical catheterization techniques by severaldecades.36 In other experiments Porter inserted a hol-low glass tube into a coronary artery through which heinfused warm, defibrinated, oxygenated ox blood toperfuse the myocardium.37 Using techniques he hadlearned in Germany and state of the art equipment,Porter studied the effects of coronary ligation on cardi-ac output in dogs. He noted the association of de-creased cardiac output and the likelihood of fatal ar-rhythmias after ligation of the coronary arteries andimplied that the extent of myocardial ischemia was amajor factor in determining these consequences ofacute obstruction of the coronary arteries.

Rudolf Kolster, a Scandinavian pathologist, hadpublished his experiments on ligation of the coronaryarteries in 1892.38 In 1896 Porter claimed, "The ex-perimental production of infarcts in the heart has beenattempted, so far as I am aware, only by Kolster andmyself, in each case with complete success."37 Porterwas familiar with Kolster's paper before the publica-tion of his own 1893 article on ligature of the coronaryarteries; a reference to Kolster appeared in the text andbibliography of Porter's manuscript, but these weredeleted in the published version.39 It seems likely thatPorter suppressed this reference to Kolster's work inhis publication in part to make his own experimentsappear more innovative and significant. Walter Baum-garten, the son of Porter's mentor Gustav Baumgarten,received his undergraduate degree at Johns Hopkins,where he worked with H. Newell Martin, and hismedical degree from Washington University in 1896.He then entered Bowditch's department at Harvard andcollaborated with Porter in several experiments. In1898 young Baumgarten complained to his father thatin his publications, "Dr. P. employs a personal style inwhich the ~go appears very frequently. "40

Porter's 1896 paper included a thorough descriptionof his operative technique. He reported that several ofthe dogs survived for various periods of time afterligation of the left anterior descending coronary artery.One dog survived four days and another fourteen and ahalf days. Postmortem examinations of these animalsrevealed "characteristic anemic infarcts . . . occupy-ing the anterior part of the septum and that part of theanterior wall of the left ventricle which adjoins theinterventricular furrow."37 Porter concluded from hisexperiments that "the rapid closure of a coronary ar-tery is followed by the death of the part which it sup-plies.''37 Addressing the controversial issue of the ex-istence of anastomoses in the coronary circulation,Porter claimed that although anatomic anastomosesexisted, they were not functionally significant in the

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context of acute occlusion of a major coronary artery.He proposed

The idea of terminal arteries is physiological, not anatomical.Terminal arteries differ from other arteries in that the peripheralresistance in the anastomosing vessels is too high to be over-come by the normal blood pressure in any of the arteries ofwhich the communicating vessels are branches. Hence the rapidclosure of any terminal artery cuts off the nutrition of its owncapillary area because sufficient blood for the life of the area cannot be sent through the communicating vessels on account of thehigh resistance in them. The resistance in the communicatingvessels, and not their size, is the factor offirst importance.. Iconclude, then, that the rapid closure of a coronary artery putsan end to the nutrition of the area which it supplied.37

Porter's experiments at Harvard were facilitated notonly by enthusiastic and knowledgeable colleagues butalso by access to assistants and apparatus that had beenunavailable to him in St. Louis. Writing in January1896, he enthusiastically informed Baumgarten thatthe staff of the department of physiology would in-crease ten the following year with the addition of fournew assistants who would receive masters degreesafter a year of advanced instruction and original labo-ratory work. Porter claimed, "The idea is chiefly ped-agogical, - to train men in physiological science; togive them habits of thought which will be useful inwhatever line of work they may take up.?" There wereimplications for the department's research output,however, and Porter predicted, "I am confident that agreat deal can be done with good men in a year'stime." He boasted, "The laboratory is now providedwith every modern means of increasing production,including stenographer, typewriter, mechanic, phono-graph, storage batteries, x ray apparatus, photographicdepartment, etc. . ." Porter and his junior col-leagues published important papers on hemodynamics,cardiac innervation, and the origin of the heart beat inthe late 1 890s. In 1898 he published a significant paperon coronary blood flow in dogs in which simultaneouspressures were measured in the carotid and coronaryarteries.

Cardiac arrhythmias attracted the attention of physi-ologists in the closing years of the 19th century. Stimu-lated by the work of MacWilliam and the earlier obser-vations of Kronecker, Porter undertook a series ofexperiments on ventricular fibrillation, which he re-ported in 1898. Porter's interest in this subject wasin part due to his curiosity regarding "the cause offailure in many previous attempts to resuscitate theheart. ..."42 Porter revealed that he was able to re-verse ventricular fibrillation that had been induced in avariety of ways, most notably by ligation of a coronaryartery, "by cooling the ventricles until all trace of

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fibrillation has disappeared, and then bringing theheart back to a normal temperature by circulatingwarm defibrinated blood through the coronary ves-

sels. '42 Thus, before 1900, Porter had studied many ofthe major physiologic and pathologic consequences ofacute obstruction of the coronary arteries. Using ad-vanced techniques and sophisticated physiologic appa-

ratus, he had investigated the effects of acute coronary

obstruction on myocardial function, the induction ofarrhythmias, and the histology of the left ventricle.

Porter collaborated with Walter Baumgarten in re-

search that led to the publication of the most compre-

hensive and most insightful article on myocardial in-farction written by an American in the 19th century.43

Baumgarten, under Porter's supervision, studied thepathologic extent of myocardial infarctions in cats anddogs after coronary artery ligations. Within severalmonths of the discovery of x-rays, they performedexperiments in which roentgenograms were made afterthe injection of radiopaque substances into the coro-

nary arteries of hearts excised from experimental ani-mals. They were interested in the relationship of ische-mia and myocardial contractility and raised issues thatare currently of great clinical interest with the introduc-tion of streptokinase therapy for acute coronary throm-bosis. Baumgarten declared, "The discovery that por-

tions of the mammalian ventricle will resume theircontractions if fed with defibrinated blood enables us

to determine how long an ischaemic area in the heartremains contractile."43 Porter and Baumgarten ob-served that loss of contractility after experimentallyinduced ischemia was reversible. They found that con-tractility persists for a time after acute coronary occlu-sion, but even if it ceased, the potential for the return ofcontractility after reperfusion of the coronary circula-tion existed for several hours. They also observed thatcontractility was most impaired in the central zone ofan infarction and least impaired at the periphery. Theclinical relevance of these important physiologic andpathologic observations is obvious in the 1980s.

Porter's experiments, and those of his assistants,were of significance in the slow but steady recognitionof the clinical syndromes of ischemic heart disease bycontemporary clinicians. A direct link between Por-ter's laboratory work and James B. Herrick's classicdescription of the syndrome of acute myocardial in-farction with survival in man was provided by twophysicians working in the laboratory of experimentaltherapeutics at the University of Chicago early in the20th century. In 1908 Joseph L. Miller and Samuel A.Matthews extended Porter's experiments on ligation ofthe coronary arteries and cited his 1896 paper as the

Vol. 71, No. 1, January 1985

single most important contribution to the subject afterCohnheim's observations published in 1881. Millerand Matthews had studied physiology under Warren P.Lombard while they were students at the University ofMichigan. Lombard had graduated from HarvardMedical School, where he worked in Bowditch'sphysiology laboratory, and subsequently studied withCarl Ludwig in Leipzig.44 Matthews began these ex-periments when he was assistant professor of experi-mental therapeutics at Rush Medical College. Millerhad received his medical degree from NorthwesternUniversity. Both had recently been elected members ofthe American Physiological Society, of which Lom-bard was a founding member.

In the first of two papers presenting the results oftheir experiments, the authors explained that theirstudies were "undertaken with the view of determin-ing the effect of drugs on animals after ligation of thecoronary arteries, believing that information gained inthis way may be directly utilized in the treatment ofangina pectoris."45 James B. Herrick was present dur-ing Miller's presentation of their results before theAssociation of American Physicians in 1908. Herrick,a prominent Chicago physician and teacher at RushMedical College, would present his classic paper onmyocardial infarction before this same society fouryears later. Joseph Miller was present at that 1912meeting and heard Herrick claim, "There are reasonsfor believing that even large branches of the coronaryarteries may be occluded, at times acutely occluded,without resulting death, at least without death in theimmediate future.' '46, 47 The critical concept that led toHerrick's classic contribution to clinical medicine wasthe recognition that sudden obstruction of the coronaryarteries was "not necessarily fatal." Among the evi-dence Herrick cited for this conclusion were the ex-periments of Porter and Miller and Matthews. Just asPorter had found, unlike Cohnheim and others, thatsome dogs survived acute ligation of the coronaryarteries, Herrick proposed that the analogous situationin man, acute thrombotic obstruction of a coronaryartery, need not always result in death.

Porter made numerous important contributions tophysiology in the 20th century. His most importantdiscoveries, however, were those made in the 1890srelating to the physiology of the coronary circulation.Porter was instrumental in founding the AmericanJournal of Physiology and was a strong advocate formeaningful student participation in sophisticated phys-iologic experiments as part of the physiology curricu-lum in American medical schools.48 49 Porter pro-claimed, "The student shall perform for himself the

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classical experiments which are the essence of the sci-ence. . The student should be trained rather thaninformed. The trained observer can and must be trustedto inform himself."49 In an effort to make high-qualityphysiologic apparatus more readily available and at areasonable cost, Porter established the Harvard Appa-ratus Company, which was "organized for the ad-vancement of laboratory teaching in physiology andallied sciences. "6* Political and personality issuescontributed to the selectioii of Walter B. Cannon asBowditch's successor, and Porter was made professorof comparative physiology at Harvard, a position heheld until his retirement in 1928.By the time of his death in 1949, the experiments

Porter had performed more than half a century earlierhad been extended by many workers and a sophisticat-ed understanding of the relationship of coronary arterydisease, angina pectoris, and acute myocardial infarc-tion was evolving. The critical role Porter's experi-ments played in the growing understanding of the path-ophysiology of coronary artery disease is an idealdemonstration of the ultimate significance of basic sci-ence observations to clinical medicine.

I thank Nancy Northup for her valuable stenographic assis-tance in the preparation of the articles in the Preludes andProgress series.

References1. Willius FA: The historic development of knowledge relating to the

coronary circulation and its diseases: introduction and preHarveianera. Mayo Clin Proc 20: 103, 1945

2. Baughman KL, Maroko PR, Vatner SF: Effects of coronary arteryreperfusion on myocardial infarct size and survival in consciousdogs. Circulation 63: 317, 1981

3. Moore S, Belbeck LW, Evans G, Pineau S: Effects of complete orpartial occlusion of a coronary artery. Lab Invest 44: 151, 1981

4. Cox DA, Vatner SF: Myocardial function in areas of heterogenousperfusion after coronary artery occlusion in conscious dogs. Circu-lation 66: 1154, 1982

5. Leibowitz JO: The history of coronary heart disease. London,1970, Wellcome Institute

6. Barger AC: The meteoric rise and fall of William Townsend Por-ter, one of Carl J. Wiggers' "old guard." Physiologist 25: 407,1982

7. Carlson AJ: William Townsend Porter: 1862-1949. Science 110:111, 1949

8. Baumgarten G: The St. Louis Medical College: an historical ad-dress. St. Louis, 1893, Nickson-Jones Printing Co.

9. The relevant correspondence between W. T. Porter and GustavBaumgarten is contained in the Baumgarten Collection, Archives,Washington University School of Medicine, St. Louis. HereafterBaumgarten papers

10. Bonner TN: American doctors and German universities: a chapterin international intellectual relations 1870-1914. Lincoln, 1963,University of Nebraska Press

11. Fye WB: S. Weir Mitchell - Philadelphia's 'lost' physiologist.Bull Hist Med 57: 188, 1983

12. Howell WH: The American Physiological Society during its firsttwenty-five years. In History of the American Physiological Soci-

*The Harvard Apparatus Company (Boston, Harvard ApparatusCompany, 1938).

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ety Semi-Centennial 1887-1937. Baltimore, 1938, AmericanPhysiological Society, p 1

13. Porter to Baumgarten, March 14, 1887. Baumgarten papers14. Porter to Baumgarten, July 29, 1887. Baumgarten papers15. Baumgarten G: Disturbances of the heart rhythm with reference to

their causation and their value in diagnosis. Trans Assoc Am Physi-cians 3: 232, 1888

16. Draper WH: On the relations of scientific to practical medicine.Trans Assoc Am Physicians 3: 1, 1888

17. Porter to Baumgarten, July 29, 1887. Baumgarten papers18. Porter to Baumgarten, December 25, 1889. Baumgarten papers19. Porter to Baumgarten, August 12, 1890. Baumgarten papers20. Porter to Baumgarten, August 5, 1891. Baumgarten papers21. Porter WT: Researches on the filling of the heart. J Physiol 13: 513,

189222. Porter to Baumgarten, May 25, 1892. Baumgarten papers23. Erichsen JE: On the influence of the coronary circulation on the

action of the heart. London Med Gazette, n.s. 2: 561, 184224. Cohnheim J, von Schultheiss-Rechberg A: Ueber die Folgen der

Kranzarterienverschliessung fur das Herz. Arch Pathol Anat (Vir-chow) 85: 503, 1881

25. Porter WT: On the results of ligation of the coronary arteries. JPhysiol 15: 121, 1893

26. Goodwin EJ: A history of medicine in Missouri. St. Louis, 1905,W. L. Smith

27. Councilman WT: Sudden death due to the heart. Boston Med SurgJ 129: 457, 1893

28. Porter WT: Uber die Frage eines Coordinationscentrum im Herz-ventrikel. Arch Ges Physiol (Bonn) 55: 366, 1893. The unpub-lished English manuscript survives. See Porter WT: Concerningthe supposed coordination-centre in the ventricles of the heart. ThePorter papers. Francis A. Countway Library of Medicine, HarvardUniversity. Hereafter Porter papers

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neurasthenia and alcoholism. J Hist Med Allied Sci (in press)32. Young JA: Anthropometric study of human growth in nineteenth-

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of American biography. New York, 1936, Charles Scribner'sSons, vol XI, part II, p 9

34. Cushing H: William Thomas Councilman, 1854-1933. Science77: 613, 1933

35. Porter WT: The effect of acute anaemia of the heart muscle on thework done by the left ventricle, 1895. Unpublished manuscript,Porter papers

36. Fye WB: Coronary arteriography: it took a long time! Circulation70: 781, 1984

37. Porter WT: Further researches on the closure of the coronary arter-ies. J Exp Med 1: 46, 1896

38. Kolster R: Experimentelle Beitrige zur Kenntniss der MyomalaciaCordis. Scand Arch Physiol 4: 1, 1892-93

39. Porter WT: On the results of the ligation of the coronary arteries.Manuscript, 1893, Porter papers

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Am J Physiol 1: 71, 189843. Baumgarten W: Infarction in the heart. Am J Physiol 2: 243, 189944. Davenport HW: Physiology, 1850-1923: the view from Michigan.

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Acute coronary occlusion always results in death--or does it? The observations of William

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