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Alexis Carrel was a Frenchman from Lyon, who gained fame at the Rockefeller Institute in New York at the beginning of the 20th century. He was the first to demonstrate that arteriovenous anastomoses were possible. Alexis Carrel was awarded the Nobel Prize for his contributions to vascular surgery and transplantation in 1912. He was a versatile scientist, who made numerous discoveries from the design of an antiseptic solution to treat injuries during the First World War to tissue culture and engineering, and organ preservation, making him the father of solid organ transplantation. Together, with the famous aviator and engineer Charles Lindbergh, they were the first scientists capable of keeping an entire organ alive outside of the body, using a perfusion machine. Due to his many dubious ideas and his association with fascism in the 1930s and during the Second World War, many of his scientific achievements have been forgotten today and taken for granted. IntroductionMany statements have been published on Alexis Carrel, who was not only a controversial figure during the first part of the 20th century, but was also, at the age of 39, the youngest scientist to receive the Nobel Prize in medicine.

1. Alexis Carrel Viaggio A Lourdes Pdf Free Download

Almost 100 years ago, Alexis Carrel was a precursor of modern vascular, cardiac and transplantation surgery ( ). He was awarded the Nobel Prize in recognition of his work on vascular sutures and the experimental transplantation of blood vessels and organs. He received this honor 78 years before Joseph Murray and Donall Thomas for their work in clinical transplantation. While Carrel is mainly known for his development of vascular sutures, his work and persistence to try to keep tissues and organs alive outside of the body are of equal importance. His ambitious idea to substitute diseased structures by healthy ones makes Carrel the father of solid organ transplantation. His dream was to conquer death. However, Carrel thought that immortality should only be accessible to carefully selected people.

In his 1935 bestseller, ‘Man, the Unknown (L'Homme, cet inconnu)’ ( ), Carrel advocated the creation of different biological human classes, by implementing a regime of enforced eugenics ruled by an intellectual elite. These political and philosophical views and his ‘undemocratic’ statements have led to major criticism and a sentiment of disgust by some ( ).Many of Carrel's scientific innovations have been forgotten because of his ideology; nonetheless Carrel should be considered as a genius and deserves full recognition for his work in the field of vascular surgery and transplantation. In this special article, we will attempt to shed light on his early experiments with tissue and organ preservation and transplantation.

We will show how Carrel precisely formulated basic concepts of static preservation and oxygenated machine perfusion over half a century before these ideas were reinvented. We will follow the career of this pioneer and describe the tightrope walk between ingenious scientific knowledge and insanity.

Vascular anastomosisIn the beginning of the 20th century, it was agreed that connecting arteries and veins was impossible. Carrel spent long hours in Lyon, in Chicago, and in New York, refining a technique for vascular anastomosis, called technique of triangulation. It consisted of placing three equidistant stay sutures and running a fine suture along the flat surface between each stay suture ( ). He also created the ‘Carrel’ patch technique for the replantation of major vascular structures during organ transplantation ( ). Through his experiments, he was able to show that arteriovenous anastomosis remains patent with a proper technique, and that the vein connected to an artery reacts against the increase of blood pressure in the arterial system by thickening of its wall ( ).

Alexis Carrel Viaggio A Lourdes Pdf Free Download

Thereby, he could demonstrate that the previously observed thromboses were not due to a biological but merely to a surgical cause. Segment of a canine vena cava transplanted on the abdominal aorta, 14 months after the operation ( ).In 1906, at the age of 33, Carrel worked with Charles Guthrie in Chicago, and together they developed an expertise in suturing vessels. They published an article on homologous transplantation of the ovary in dogs ( ). Previous experiments had shown that the transplantation of young ovaries without vascular anastomoses was possible, while the transplantation of adult ovaries remained unsuccessful. Carrel argued that these negative results were due to an improper technique; later he managed to successfully transplant adult ovaries using a peritoneal flap, the method of ‘transplantation in mass’, which avoided the separation of small vessel branches. The peritoneal flap included the ovary and a part of the Fallopian tube, united to segments of the aorta and vena cava.

Perfusion experiments—prerequisite for the use of DCD graftsWhile Carrel was successful in the culture of tissues, his attempts to maintain whole organs alive outside of the body failed repeatedly. For a long time, he found no device capable of playing the role of the heart and lungs. In this endeavor, Carrel was unexpectedly aided by the aviator and engineer Charles A. Lindbergh became interested in organ perfusion as a result of an illness of his sister‐in‐law, who had rheumatic heart disease.

Lindbergh designed a continuous medium‐circulation flask consisting of a culture chamber ( ). The perfusate consisted of blood serum, cysteine, insulin, thyroxins, glutathione, ascorbic acid and phenol red for pH control. A gas mixture of 40% oxygen, 4% carbon dioxide and 56% nitrogen served as a driving force to pump the fluid and as oxygenation source of the tissue.

The harvesting of whole organs (cat hearts and thyroids) was performed by extirpation of the organ with its surrounding arteries, veins, nerves and lymph vessels. During organ retrieval, the donor cavity and the graft were constantly soaked in Carrel–Dakin's solution to avoid bacterial contamination.

The volume of the perfusate was calculated two times greater than that of the organs. The artery of the organ was connected and the organ was perfused in a pulsatile manner. The apparatus was kept in an incubator at a temperature of 37–38°C.

Circulation started about 1 h after the death of the donor animal. The number of pulsations was adjusted in most experiments to 60 per minute, the systolic pressure to 120 mmHg, and the diastolic pressure to 60 mmHg. Thyroids were amazingly well preserved with pulsating arteries after a period of up to 30 days. No embolism occurred; the proof of organ function was documented by the metabolism of 7 mg of glucose per 24 h.

Cat hearts maintained their contractions for about 12 hours. Diagram (A) and photograph (B) of the original Lindbergh–Carrel perfusion pump. This sterilized machine was completely built in glass and permitted ex vivo perfusion of an entire organ for the first time in history in 1935.

The organ was placed in a chamber 4 and perfused by blood serum enriched by amino acids. The perfusate was allowed to drain passively by gravity out of the organ in a reservoir chamber 18. Circulation of the fluid was maintained by gas insufflation (40% oxygen, 4% carbon dioxide and 56% nitrogen) through filter bulbs 1 & 2.

The fluid ran through the chamber by gravity, because of the difference in fluid pressure between the inlet and the outlet tubes. Several floating valves 9 &16 prevented backflow in the organ. Sterility was achieved by implementation of a silica sand filter for the perfusate. More than 900 successful perfusion experiments were performed with this device ( ) (Reproduced from The Journal of Experimental Medicine, 1935, 62: 402–431. Copyright 1935, The Rockefeller University Press).Between 1935 and 1939, almost 900 perfusion experiments were carried out in Carrel's laboratories using the Lindbergh RIMR (Rockefeller Institute for Medical Research) perfusion pump.

One shortcoming of the machine was that only very small organs fitted in the chamber. However, the apparatus worked so well that no experiments had to be interrupted due to malfunction.

Unfortunately, the enthusiasm of Carrel was not shared by others as the apparatus was not used again after his retirement.Even by modern standards, the results obtained with this machine may be judged as very good. It is surprising, therefore, that this work was not enhanced systematically in other laboratories. Instead, serious doubts were cast on the validity of Carrel and Lindbergh's experiments until the apparatus was reproduced in 1964 at the United State Naval Medical Research Institute, aided by Lindbergh ( ).

Lindbergh designed a new perfusion apparatus that could accommodate larger organs than the original Lindbergh–RIMR pump. The latter was named the Lindbergh NMRI (Naval Medical Research Institute).Modern perfusion systems for livers and kidneys still rely on many basic principles, which had already been described by Carrel and Lindbergh.

It is noteworthy that after an era of static cold storage during the past three decades, current promising results have been achieved to optimize DCD livers and kidneys by machine perfusion techniques ( ). These devices resemble Carrel and Lindbergh's machine in several ways; the perfusate is recirculated with low volume, filtrated, oxygenated and perfused by pressure control. Future experiments will show if viability of DCD grafts can fully be reactivated by these approaches, which would underline Carrel's hypothesis from 100 years ago. Tissue engineeringAlthough many researchers of the time had postulated that the in vitro life of cultivated tissue was very short, Carrel was convinced that the aging and death of cell cultures were preventable. It was therefore conceivable for him that elemental death might be postponed indefinitely by a proper artificial nutrition ( ). Following this hypothesis, cells were maintained and cultivated for more than 11 years by washing with Ringer solution and changing the medium ( ).

In 1923, he described a method, which allowed for the cultivation of pure strains of fibroblasts, epithelial cells and leucocytes ( ). The new principle here was to change the medium without disturbing the tissues and avoiding bacterial contamination. For this, he used flat, round flasks, thereinafter referred to as Carrel flasks, and observed meticulous asepsis.

With his perseverance, Carrel demonstrated that tissue culture was a method of practical value for experimental design ( ), keeping in mind that these experiments were accomplished before the era of antibiotics. Numerous future experiments to further develop tissue culture, and finally, tissue engineering were based on these early findings. ‘Man, the unknown’—philosophical considerationsAlexis Carrel experienced severe setbacks and disappointments—having to leave Lyon, and then go to Montreal, then Chicago, and, finally, New York. These seeming adversities were overcome by a courageous man.

He was neither afraid of new ideas nor of making mistakes, an attitude most likely related to his Jesuit education. Driven by personal experiences, as a young scientifically motivated doctor accompanying a group of pilgrims to Lourdes and, later, by the political rise of fascism, he wrote, ‘Man, the Unknown’, published in 1935 ( ). This book did not focus on physiology alone, but rather on philosophy and ideology.

The book rapidly became a bestseller and was translated in 20 languages. Through more than 300 pages, Carrel diagnosed the disease of the Western civilization, and then proposed a cure. Carrel called for a new kind of politics for a system, in which scientists sorted individuals according to their attitudes and abilities, thus, creating ‘universal efficiency’. This species of human had to be protected from pollution by genetically unfit individuals. This book triggered major hostile reactions, from the first date of publication until today. Carrel's ideas and statements implicate ambivalent rather than clear association to fascistic or anti‐Semitic beliefs. Suspicions were possibly misleadingly reinforced by his friendship with Charles Lindbergh, who received a medal of honor on behalf of Adolf Hitler in 1936 and his affiliations with the Nazis.

Carrel's views on eugenic theory were ‘recycled’ by the far‐right wing party, the National Front led by Jean‐Marie Le Pen, in the beginning of the nineties. With the name of Alexis Carrel being injected into the political debate, a majority of French concluded that these views brought dishonor to the country. Consequently, his name was removed from streets in more than 20 French cities; the Alexis Carrel Medical Faculty in Lyon was renamed in 1996. Immortality—Carrel's visionCarrel worked hard to find the key mechanism for life.

We may speculate that his father's early death contributed to this obsession in many ways. In this context, Alexis Carrel probably identified with his father very early in life by the adoption of his father's name at age 5. He grew up during his further education in Jesuit's school, to become a very ambiguous and focused person, learning to fight to accomplish his aims. As an adult, he spent most of his time exploring the function and viability of cells and organs, always searching to overcome the finiteness of life.The numerous of Carrel's contradictions remained too difficult for the public, and even many scientists, to understand. He was a brilliant physiologist who believed in prayer cures.

He was a Catholic who supported birth control. He admired his wife, but believed higher education was wasted on women. He loved children, yet never had any.

He was a laboratory scientist who thought of himself as a philosopher ( ).The goal of this article was to show the many scientific achievements and ideas of Alexis Carrel. His political inclination and dubious philosophy cannot be balanced by any scientific achievement. However, his scientific works, such as the anastomosis of vessels, the concept of cold preservation and his pioneer work in extracorporeal machine perfusion, were far ahead of his time. If we look nowadays at the success of the transplantation of solid organs, we should keep this in mind.