The life and career of the great French mathematician and politician Paul Painlevé is described. His contribution to the analytical theory of nonlinear differential equations was significant. The paper outlines the achievements of Paul Painlevé and h
A Psion microcomputer controlled infusion system for alfentanil was assessed for the provision of post-operative analgesia in 14 patients who had undergone aortic bifurcation graft surgery. The system employed a pharmacokinetic model working in real
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Latour is widely considered a critic and renewer of research in the social sciences. The ecologically minded Left has also acclaimed him as a theorist interested in bringing nature back both into sociological theory and into society and politics. To
Jacques Oudot and His Contribution to Surgery of the Aortic Bifurcation Jean Natali, MD, Neuilly, France
In the beginning of 1950, I was in my second year of residency. I had heard that an Assistant Surgeon at the Paris Hospitals was looking for a young colleague to work with him at the Animal Experimental Center of the Anatomy Laboratory, rue du Fer h Moulin. I remember quite well the day I met Jacques Oudot for the first time. It was on a winter afternoon in the back of the gardens which lined the dissection pavilions. The barking of dogs added a living contrast to the ghostlike, inert forms under the sheets that could be seen though the windows! Jacques Oudot was waiting for me in his office, just next to the operating room for animal surgery. He had just finished operating and I can still see the man, somewhat massive, his shoulders a bit shrunk that made people think he suffered from rheumatism . His eyes were bright, with a sort of expression on his face that combined jubilation with determination (Fig. 1). I told him that I knew little about vascular surgery, and he was very frank and very direct when he answered, "I deeply need somebody to help me here, but in exchange, I will show you how to cut at least one year off your studies. Are you really sure that you want to work hard?" After saying yes, quite timidly and full of anxiety, and after a few training sessions, I became familiar with experimental surgery of the aortic bifurcation. These experimental studies set the scene for the first bifurcation graft of the aorta in human beings at the end of that same year I950 . It had been known for several years that occlusion of the aortic bifurcation could be responsible for ischemic modifications in the lower limbs. Surgeons such as Graham (1814), Barth (1848), CruveilFrom the Department of Vascular Surgery', American Hospital, Neuitly, France. Reprint requests: J. Natali, hiD, 66 boulevard Malesherbes, 75008 Paris, France. 185
hier (1823), and Welsch (1898), cited by Ralph Deterling , had reported a total of 59 cases of occlusion of the aorta. It was Ren6 Leriche  who first described the occlusion of the aortic bifurcation as a cause of circulatory insufficiency of the lower limbs. This was on December 5, 1923, at the Soci6t6 de Chirurgie which was later to become the Academie de Chirurgie. The last lines of his communication read: "the ideal treatment [ . . . of occlusion of the aortic bifurcation] would be excision of the occluded part of the vessel and reestablishment of arterial continuity if at all possible. The problem is that, unfortunately, this ideal will probably never be achieved". During the next few years, Leriche worked at improving peripheral circulation by sympathectomy but did not publish any salient results. It was only after the dangers of aortography decreased, and this investigation could be performed readily that he became interested in the problem once again. In 1940 he described the syndrome that carries his name. In an article entitled "Syndrome of terminoaortic obliteration due to arteritis" published in the Presse M#dicale, he reported five such cases, as well as the first aortic resection combined with lumbar sympathectomy . He underscored the frequency of associated impotence. In 1948, Lefiche and Morel published an article in Annals of Surgery  and the syndrome became known in the United States. Between 1940 and 1949, several surgeons performed either sympathectomy or aortectomy, and from these operations I was able to collect 27 cases for my thesis written in 1952 . In 1945 Crafoord  operated on the first case of aortic coarctation, followed soon after by Gross. The necessity of reestablishing aortic continuity using an arterial substitute when the stenotic segment was long made Gross reconsider the problem
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of arterial grafts . The principles of vascular anastomosis had been established by the work of Carrel and Guthrie , but, until then, arterial grafts did not have any clinical application. In the classical series of DeBakey and Simeone , of 2,471 arterial wounds sustained by American soldiers during the Second World War, only 40 restorations were possible; at the same time 23 amputations were necessary. In Germany several dozen cases were reported, about the same number as reported after the First World War. At this time, the debate was focused on whether it was best to use living or cadaver grafts, the latter being fixed in 4% formalin as advocated by Nuboer  or preserved by cold as proposed by Fontaine .
EXPERIMENTAL STUDIES Results of the experimental studies performed on dogs with Jacques Oudot were published in my "Gold Medal" memoir, my thesis  and in other papers [14-16]. This experimental work can be divided into three distinct parts: (1) Creation of chronic occlusion of the aortic trifurcation. As the canine internal iliac arteries originate in a common trunk, the dog has a trifurcation rather than a bifurcation (Fig. 2). (2) Analysis of the effects of transient acute occlusion of the infrarenal aorta. (3) Grafting of the aortic trifurcation with preserved homografts. Creation of chronic occlusion of the aortic trifurcation
We did not reproduce the previous studies of Montreid and Halsted  who had shown that complete ligation of the aorta was responsible for immediate paraplegia. In the rare cases published in the literature in which paraplegia did not occur, the aorta ruptured and was associated with fatal hemorrhage. Attempts to initiate thrombosis by subendothelial injection with either morrhuate sodium or 40% glucose were failures. As well, the results of subadventitial injection of toxic irritating substances according to Laplane's technique  were not conclusive. At that time a new, very active, thrombin called Topostasine from Roche Hoffmann was available. The solution contained 500 units of active substrata per ml (one unit was capable of coagulating one ml of a standard solution of fibrin in 15 seconds). We were thus able to reproduce aortic occlusion with this method. Occlusion, however, occurred very suddenly and resembled acute thrombosis. It was
Fig. 1. Jacques Oudot in 1951 (1913-1953).
not possible to reproduce local thrombosis so that complete occlusion could occur progressively. There was only one technique with which we were able to reproduce chronic occlusion. That was by enveloping the trifurcation branches with cellophane. With this technique, we obtained three instances of complete occlusion of the aortic trifurcation of the dog (Fig. 3) associated with intermittent claudication of the hind legs without paraplegia. Effects of transient acute infrarenal aortic occlusion
We then studied the effects due to clamping of the infrarenal aorta because in the technique we were to use it was necessary to interrupt the circulation completely for two to three hours. This entailed the routine study of the effects on carotid and femoral arterial pressure, kidney volume, diuresis, respiration, and the degree of anesthesia induced by crossclamping of the infrarenal aorta during two and a half hours. It goes without saying that, because of the lack of electronic measuring devices at that time, these measurements were far from perfect. Nonetheless, it was possible to demonstrate that clamping was perfectly tolerated by the kidney, that a small
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Fig. 2. Abdominal aorta and its branches in the dog (drawing courtesy of Claude Madier). 1 = inferior vena cava; 2 = ureter; 3 = Spermatic artery; 4 = abdominal aorta; 5 = inferior mesenteric artery; 6 = lumbar artery; 7 = femoral artery or crura; 8 = communicating trunk of the hypogastric arteries; 9 = bladder.
degree of distal irrigation continued in spite of clamping, and that, after declamping, all parameters returned rapidly to within normal values. Performance of homografts of the aortic trifurcation
The preservation solution chosen by Oudot was that of Tyrode modified by Hanks. The formula was as follows: Sodium chloride Potassium chloride Sulfate of magnesium 70 H 2 Magnesium chloride 60 H2 Calcium chloride Disodium phosphate NA2H Monopotassium phosphate Glucose Phenol red per one liter of water.
8g 0.40 g 0.20 g 0.20 g 0.14 g 0.06 g 0.06 g 1g 5 cc
Fig. 3. Experimental chronic occlusion of aortic trifurcation in the dog.
This solution was placed in resistant glass flacons sterilized by autoclave at 120°C for 20 minutes. Sodium bicarbonate solution was added until the yellow solution became pink. Heparin, 100,000 units, was then diluted into 250 ml of solution, and 100,000 units of penicillin were added per flacon. The grafts were retrieved from animals sacrificed at the animal pound and were prepared by ligation of small collateral branches at their origin with linen sutures and then by removal of excessive adventitia which, if curled up, would have hindered suturing. The grafts were then placed in the conservation solution and refrigerated. They were used from a few days to four weeks later. Starting in the mid1950s, we added homologous serum to Hanks' solution and in 1952, Oudot added embryonic ewe extract. These grafts remained grossly normal and supple for three to four weeks and were amenable to suture purchase just as were fresh arteries. Histologically, however, changes occurred as shown by Gauthier-Villars and Oudot . The endothelium swelled and tinctural changes appeared in the cells of the middle tunica. After a few weeks' time, the entire structure was substantially modified.
Fig. 4. Arteriogram after aortic trifurcation graft in the dog.
It was still possible, however, to impregnate the endothelium with silver nitrate, which was considered at that time as evidence of viability. In keeping with this hypothesis was the possibility of obtaining positive tissue cultures. Pathohistological study of the graft in place  showed that the intima was thickened due to proliferative endarteritis. Recipient endothelium was discontinuous. There was a tendency for the media to lose its smooth muscular fibers. The elastic membranes were dense and less festooned than normal. The adventitia was the site of prolonged inflammation leading to young fibroblastic tissues which constituted a solid external cover. During this same year 1950, approximately 20 dogs were operated on by Oudot or myself [Figs 4,5]. Mortality was high in the beginning. Results improved starting in September and October 1950 as 8 of 10 dogs survived with patent grafts. The reasons for this improvement were, undoubtedly, increased experience, use of less traumatic clamps, and above all, availability of fine needles. We continued these experiments aJl during 1951.
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Fig. 5. Graft retrieved after six months of patency.
One dog survived 10 years; operated on July 5, 195t, the dog died on October 3, 1961 and we were able to make a histopathological study of the homograft 10 years after insertion (Figs. 6,7).
FIRST CLINICAL GRAFTS OF THE AORTIC BIFURCATION On November 14, 1951, Oudot decided to operate on a 5 l-year-old woman with occlusion of the aortic bifurcation associated with trophic disorders on his left leg. The operation was conducted through an extraperitoneal approach. The distal anastomoses were relatively easy to perform on the left, more difficult on the right. The immediate postoperative course was satisfactory. Excellent pulsations were palpated on the left but not on the right. Aortograms were obtained, confirming the absence of patency in the right limb of the graft (Fig. 8). Oudot reoperated on this patient on May 8, 1951, and performed the first crossover bypass published in the literature by inserting a graft between the two external itiac arteries coursing in front of the bladder. This pa-
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Fig. 6. Gross aspect of homograft of dog 10 years after operation.
tient died three-and-a-half years later. The autopsy showed that the graft had thrombosed . The second bifurcation graft took place on May 16, 1951 (Fig. 9). Recovery was uneventful as adequate circulation was reestablished bilaterally. Before his death in 1953, Jacques Oudot operated on 11 other patients. There were four early deaths, whereas seven patients survived with satisfactory
Fig. 7. Histopathological aspect of homograft 10 years after implantation. Note disappearance of elastic fibers in media on bottom.
Fig. 8. Postoperative aortogram of first graft of aortic bifurcation (right lilac arteries are not injected but right common femoral artery is visible). Crossover bypass was performed (first reported in literature) a few weeks later with excellent results.
results. I was able to follow one of these patients myself for nearly 10 years. A follow-up arteriogram obtained nine years later is shown here (Fig. 10). As soon as these results became known, several other surgeons followed the example. In Great Britain, Rob  and Cockett  published reports of 13 and 12 patients, respectively, having undergone bifurcation grafts as of 1956. DeBakey reported 22 cases in 1954 . In the same year, with Patel and Faurel, we reported 18 cases with two deaths and nine excellent results, while four patients were improved and three were failures . In 1956 the first prosthetic grafts made their appearance, but they only became operational and used readily in 1958-1959. Faurel, however, continued to use homografts until his death in 1965. It is possible that homografts may be used for other indications someday. This sketch of Jacques Oudot would not be complete without mentioning the other aspects of his life. Oudot came to surgery relatively late. He started his career in chemistry and pharmacy and was a resident in pharmacy before becoming a resident in
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Fig. 9. Preoperative aortograms of second graft of aortic bifurcation showing complete thrombosis of aorta proximal to bifurcation. Fig. 11. Jacques Oudot during Annapurna Expedition (courtesy of Marcel Ichac).
Fig. 10. Follow-up arteriogram nine years after homograft, Note small dilatation of left part of aortic segment.
surgery. He wrote his thesis on active vasodilatation in 1946, which heralded his interest in vascular disease. In a few years' time his list of publications was impressive. His death in 1953 was so sudden that some of his work, in particular kidney transplants with Auvert and grafts of the aortic arch performed with myself, was never published. Jacques Oudot also excelled in mountaineering. In 1950, just a few months before his first graft of the aortic bifurcation, he participated in another great first--the ascension of the Annapurna Mountain in the Himalayas (26,502 feet). Henri Mondor related  how one morning Jacques Oudot came to ask him if he could take leave to participate as surgeon and member of the Himalayan expedition which was being proposed. Said Mondor, " H o w could I say no to this kind, college boy who wanted to go off on such a highly competitive and outstanding vacation site?" This expedition was prepared with the same rigor and care as everything else he did. You know the rest of his story as related magnificently in Maurice
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Fig. 13. Jacques Oudot injecting vasodilatators through femoral artery at 6,000 meters altitude for severe frostbite of the distal lower limb (courtesy of Marcel Ichac),
Fig. 12. Reconnaissance of North Face of Annapurna with Lionel Terray followed by Jacques Oudot (courtesy of Marcel Ichac). H e r z o g ' s A n n a p u r n a : P r e m i e r 8000  a n d M a r c e l I c h a c ' s R e g a r d s vers l ' A n n a p u r n a  (Figs. 11, 12). A f t e r a c h i e v e m e n t o f the m o u n t a i n ' s s u m m i t , c a m e the difficult t a s k s for w h i c h J a c q u e s O u d o t s h o w e d the s a m e c o u r a g e a n d scientific a n d p r o v i d e n t i a l d e v o t i o n . It has b e e n said that " t w o b r a v e p e o p l e a m o n g all k n o w this a n d o w e him their l i v e s "  (Fig. 13). J a c q u e s O u d o t r e l a t e d this u n i q u e e x p e r i e n c e in a e x c i t i n g article in 1951 . J a c q u e s O u d o t was o n e of t h o s e E u r o p e a n g i a n t s P e t e r M a u r e r o f M u n i c h t a l k e d a b o u t in his s p e e c h at the I n t e r n a t i o n a l U n i o n o f A n g i o l o g y in R o m e in 1989 . It is a p p r o p r i a t e that, at the h o u r o f the birth o f U n i t e d E u r o p e , h o m a g e to J a c q u e s O u d o t be m a d e in a n i n t e r n a t i o n a l j o u r n a l .
REFERENCES 1. MONDOR H. Jacques Oudot. Presse Med 1953;58:1181. 2. OUDOT J. La greffe vasculaire dans les thromboses du carrefour aortique. Presse Med 1951;59:234-236.
3, DETERLING RA Jr. In: Vascular Surgery Principles and Techniques. Appleton-Century, 1984. 4. LERICHE R. Des oblit6rations art6rielles hautes (oblit6ration de la terminaison de l'aorte) comme causes des insuffisances circulatoires des membres inf6rieurs. Bull Mere Soc Chir Paris 1923;49:1404-1406. 5. LERICHE R. De la r6section du carrefour aorto-iliaque avec double sympathectomie tombaire pour thrombose art6ritique de l'aorte le syndrome de l'oblit6ration termino-aortique par art6rite. Presse Med 1940;48:601-604, 6. LERICHE R, MOREL A. The syndrome of thrombotic obliteration of the aortic bifurcation. Ann Surg 1948;127: 193-206. 7. NATALI J. Chirurgie de la bifurcation aortique: 6tude exp6rimentale et clinique. ThOse M~decine Paris 1952. 8. CRAFOORD C, NYLIN G. Congenital coarcation of the aorta and its surgical treatment. J Thorac Surg 1945;14:345355. 9. GROSS RE, BILL AH Jr, PIERCE EC. Methods for preservation and transplantation of arterial grafts. Observations on arterial grafts in dogs. Report of transplantation of preserved arterial grafts in 9 human cases. Surg Gynecol Obstet 1949;88:689-695. 10. CARREL A, GUTHRIE CC. Uniterminal and biterminal venous transplantation. Surg Gynecol Obstet 1906;2:266269. 11. DE BAKEY ME, SIMEONE FA. Battle injuries of the arteries in World War II: an analysis of 2471 cases. Ann Surg 1946;123:534-579. 12. NUBOER JF. Traitement chirurgical de certaines coarctations de l'aorte, en utilisant des homogreffes fix6es darts une solution de Formaline 4%. Rapport du 56~me Congres Franqais de Chirurgie Paris. Paris: Presse Universitaire de France 1954; pp 318-321. 13. FONTA1NE R, DUBOST C. Les greffes vasculaires. Rapport du 56 ~me Congr6s Franqais de Chirurgie. Paris: Presse Universitaire de France, 1954, pp 164-312.
14. PATEL J, F A U R E L J, NATAL1 J. Traitement chirurgical des thromboses de la bifurcation aortique. Minerva Cardioangiol Europea 1957;5:125-137. 15. PATEL J, NATALI J. R6gles actuelles de la chirurgie de la fourche termino-aortique. J Chir 1951 ;67:599-630. 16. PATEL J, NATALI J, ORCEL L. Greffe de bifurcation aortique de chien datant de 10 ans. Presse Med 1964;72:231233. 17. HALSTEAD WS. Surgical Papers I. Baltimore: Johns Hopkins Press, 1924. 18. LAPLANE R. Le r61e de I'adventice dans la g~nese des art~rites: 6rude exp~rimentale. Ann Med 1950;51:397--445. t9. GAUTHIER-VILLARS P, OUDOT J. Greffes ar6rielles homog~nes et autog+nes (~tude exp~rimentale). Presse Med 1951 ~9:1227-1230. 20. DUBOST C, BINET JP. Les greffes d'aorte. Rapport du 56eme Congr6s Franc~ais de Chirurgie. Paris: Presse Universitaire de France, 1954; pp 21. ROB C. Obliterations of the aortic bifurcation (Leriche's
24. 25. 26. 27.
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syndrome) surgical treatment. Minerva Cardioangiol Europea 1957;5:110-116. COCKETT FB. Obliteration du carrefour aortique (syndrome de Leriche). Minerva Cardioan~iol Europea 1957;5: 143. DE BAKEY ME. Les greffes d'aorte. Rapport au 566me Congr~s Fran~ais de Chirurgie. Paris: Presses Universitaires de France, 1954; pp HERZOG M. Annapurna Premier 8000: R~cit de l'Exp~dition Franqaise 1950 (1 l'Annapurna. Paris: B. Arthaud, t951. ICHAC M, HERZOG M, Regards vers I'Annapurna. Paris: B. Arthaud, 1951. OUDOT J. Observations physiologiques et cliniques en haute montagne. Presse Med 1951;59:297-300. MAURER PC. On the shoulders of giants: vascular surgery the European heritage and contributions. In: Advances in Vascular Pathology. Amsterdam: Excerpta Medica, 1989; pp 3-8.