Carrel Rejoins Severed Blood Vessels

Date 1902

Alexis Carrel’s precise procedures for aseptically rejoining blood vessels increased the range of possible surgical procedures and contributed to the realization of organ transplantation.

Locale Lyons, France; Chicago, Illinois

Key Figures

• Alexis Carrel (1873-1944), French surgeon and biologist
• Charles Claude Guthrie (1880-1963), American surgeon

Summary of Event

As Alexis Carrel noted in 1908, “The idea of replacing diseased organs by sound ones, of putting back an amputated limb or even of grafting a new limb on a patient having undergone an amputation, is doubtless very old.” Despite the antiquity of the desire, however, the dream remained unrealized until surgeons were able to restore circulation through grafted organs and limbs. Carrel developed a procedure in 1902 for rejoining severed arteries; without this procedure, modern transplantation surgery would be impossible.

On one level, it seems like an easy operation—simply take the two ends of severed vessels and sew them together. Blood, however, presents special difficulties. Although it normally clots quickly when exposed to air, it usually remains unclotted inside a vessel. Its ability to stay unclotted depends on an intact inner membrane of a vein or artery: the tunica intima. If this surface is unhealthy or has foreign bodies on it, blood clots may form in the vessel. This condition, called thrombosis, is fatal if the blockage occludes (closes) the entire vessel.

Other surgeons before Carrel had attempted to rejoin severed vessels, but their attempts had usually ended in thrombosis and death. There were two general methods for these operations. Surgeons either sewed together the middle and outer layers of the vessel (the tunica media and tunica externa or adventitia) or inserted a fine magnesium tube into the lumen and joined the vessel together. The success of these operations depended on strict asepsis and an accurate union of the ends. Several experimental successes were achieved with these methods, but their translation into surgical practice was difficult to accomplish.

According to most accounts, Carrel became interested in this procedure when Sadi Carnot, the president of France, was assassinated in 1894. The bullet that struck Carnot had severed an artery, and the president, despite the ministrations of surgeons, had bled to death. Carrel, who had demonstrated much scientific acumen as a youth, turned his attention to the problem of rejoining blood vessels. He mastered fine stitchery and asepsis and introduced paraffin-covered threads and needles. The key to his procedure was that he rolled back the ends of the vessels and sewed these ends together; the blood then continued to flow uninterrupted through the artery’s smooth inner surface. This step allowed for the resumption of circulation. Carrel finally succeeded in 1902. In that year, he later announced, he had transplanted kidneys in dogs on more than one occasion. Although all the animals died because of septic complications, the kidneys began to produce urine immediately, demonstrating that the joined vessels had, in fact, restored circulation through the organ.

In 1905, working with Charles Claude Guthrie, Carrel transferred segments of a jugular vein into a carotid artery. The surgeons discovered that the vein soon underwent structural changes—the caliber of the lumen enlarged and the walls became thicker—to accommodate increased blood pressure. Vein-to-artery grafts often ended in thrombosis, however, so they devised methods to store arterial sections for later use. They discovered that segments chilled almost to freezing and then gently warmed were still viable after days or weeks of such treatment.

In the course of these experiments, Carrel soon discovered the limits of grafting or transplantation. He noted that grafting pieces of blood vessels or organs taken from the same animal (he called them “autoplastic donors”) succeeded, whereas tissues from other animals (“heteroplastic donors”) were soon rejected by the host. The further away the species was genetically, the more rapid the rejection. He also noted that blood from unrelated donors usually was fatal to the recipient.

Carrel used his surgical techniques to attempt ever more daring grafts and transplants. He and Guthrie continued to work on kidney transplants after 1905 and achieved much greater success than in Carrel’s 1902 attempts. They eventually transplanted other organs and limbs. Although the animals died, Carrel and Guthrie demonstrated the technical feasibility of these operations on humans.

Despite his surgical finesse, Carrel never engaged in clinical practice. All his work, done either at the University of Chicago in 1905 and 1906 or later at the Rockefeller Institute, was entirely devoted to research. The application of Carrel’s work to human subjects—or, more likely, the rediscovery of his work—depended on other surgeons. In 1912, Carrel was awarded the Nobel Prize in Physiology or Medicine for his work on the surgery of blood vessels.

Significance

Carrel’s development of a method for rejoining severed blood vessels was a necessary, but not sufficient, condition for the realization of the ancient dream of organ transplantation. In order for that dream to be realized, medical professionals needed to understand the physiology of transplantation as well as its technique. Carrel recognized this problem. He had noted, for example, that blood from nonrelated donors usually was fatal for recipients. Also, rejection phenomena had demonstrated that the underlying issues affecting the success of transplants were biological, not mechanical. Once these physiological issues were settled, Carrel’s techniques entered clinical surgery.

Carrel’s work had to be complemented by many other discoveries before its impact on surgery could be fully realized. Karl Landsteiner’s discovery of blood types, published in 1901, solved the puzzle of why some transfused blood, but not all, was toxic to recipients. During the years between World War I and World War II, several scientists worked to devise reliable methods for the storage of blood. Peter Medawar’s insights into immunity explained heteroplastic rejection.

Many of the techniques that Carrel developed in the early years of the twentieth century were not applied clinically until after World War II. The first documented cases of artery storage and transplantation occurred in the United States in 1948 and in France in 1952. Although the development of fabric grafts eventually ended most concerns about vessel storage, the use of such grafts would be impossible without Carrel’s technique. His discovery that veins could be grafted successfully to arteries is the foundation of much of the bypass surgery performed today.

Carrel and Guthrie’s work on kidney and limb transplantations is a direct ancestor of current transplant procedures. The dazzling virtuosity that surgeons display during these operations depends on the careful suturing of vessels—a procedure first accomplished by Alexis Carrel.

Bibliography

Carrel, Alexis. Man, the Unknown. New York: Harper & Bros., 1935. Carrel presents his views on humanity’s future. Some saw this volume as prophetic when it was first published; others viewed it as unfounded speculation.

‗‗‗‗‗‗‗. The Voyage to Lourdes. Translated by Virgilia Peterson. New York: Harper & Bros., 1950. A third-person narrative written by Carrel about his visit to Lourdes in 1903. Documents his earliest interests in the relationship between religion and science.

Haeger, Knut. The Illustrated History of Surgery. Ottawa: Canadian Medical Association, 1998. Clearly describes Carrel’s achievement in the context of other surgical advances of the early twentieth century, such as Rudolph Matas’s strengthening of arterial walls threatened by aneurysm and Friedrich Trendelenburg’s “high ligature” operation for varicose veins.

Hardy, James D. “Transplantation of Blood Vessels, Organs, and Limbs.” Journal of the American Medical Association 250 (August 19, 1983): 954-957. JAMA reprinted Carrel’s 1908 article “Results of the Transplantation of Blood Vessels, Organs, and Limbs,” and Hardy commented on it. He reiterated what earlier critics of Carrel’s work had noted, that “the new investigator beginning arterial transplantation research would do well to check first to see if Dr. Carrel did not publish the proposed research at the turn of the century.”

Majno, Guido. The Healing Hand: Man and Wound in the Ancient World. Cambridge, Mass.: Harvard University Press, 1975. A landmark book in the history of surgery that addresses, in clinical and surgical detail, wound management in antiquity. Describes how ancient surgeons manipulated vessels during surgery or closed wounds after it to avoid what is now known as shock, inflammation, and infection.

Malinin, Theodore I. Surgery and Life: The Extraordinary Career of Alexis Carrel. New York: Harcourt Brace Jovanovich, 1979. A popular account that examines the two main aspects of Carrel’s life: as a pioneer in surgical techniques and as a visionary for a political utopia.

Nuland, Sherwin B. Doctors: The Biography of Medicine. New York: Alfred A. Knopf, 1988. A popular history of medicine told from the perspective of its famous practitioners. The chapter on organ transplantation discusses Carrel’s early work as a necessary stage for the successes achieved in kidney transplantation in the 1950’s.

Tilney, Nicholas L. Transplant: From Myth to Reality. New Haven, Conn.: Yale University Press, 2003. This book, suitable for both professionals and laypersons, traces the evolution of organ transplantation from its beginnings in the imaginations of human beings to its current status as accepted treatment. Describes early transplantation attempts, the evolution of surgical technique, the first successful kidney transplant (in 1954 between identical twins), the introduction of the concept of host tolerance, and scientific advances for suppressing the immune system.

Wilson, Leonard G. Medical Revolution in Minnesota: A History of the University of Minnesota Medical School. St. Paul, Minn.: Midewiwin Press, 1989. Outside of Boston, most of the early clinical research and attempts at transplantation were done at the University of Minnesota. The chapter titled “The Development of Organ Transplantation in Minnesota” documents this work based on Carrel’s surgical procedure.