3406 CardioPulse

doi:10.1093/eurheartj/ehx697 Pioneers in transplantation.... Vladimir Petrovich Demikhov (1916–1998)

A pioneer of transplantation ahead of his time, who lived out the end of his life as an unknown and in poor circumstances

Great spirits have always encountered violent opposition from mediocre minds Albert Einstein

When in 1996 the world’s famous cardiac surgeon Michael DeBakey visited to participate in coronary artery bypass grafting on Russia’s President Boris Yeltsin, his first question was ‘May I pay the last honours to Professor Demikhov?’ there were two errors in his short sentence—not only had Demikhov never been awarded a the replacement device working by an electric motor was Professorship, but he was alive and living in a very small apartment on turned on. After 16 min on the device the dog began demonstrating the outskirts of Moscow. obvious vital signs (respiratory, ocular and other reflexes)’. Sadly, DeBakey received no answer..., nobody knew who Later in his book ‘—is it possible?’ (1959) Demikhov was. Demikhov provided the drawing of his device (Figure 1). And also Vladimir Petrovich Demikhov (1916–1998) was born on 18 July stated that ‘The final goal of our experiments was to make transplan- 1916 in the village of Yarizhenskaya in Russia’s Volgograd region into tation of the heart and other organs in humans possible’. a family of peasants. His father was killed in 1919 during the Russian Today it is hard to believe that in 1937 Demikhov, a 21-year-old civil war and his mother, being minimally educated, put all her energy student, was able to: and time into efforts to provide a higher education for all three of her (1) use ether anaesthesia, children. (2) use prolonged pulmonary ventilation, Legend has it that as a 13-year-old boy Volodya (Vladimir) (3) perform thoracotomy and preparation of cardiac vessels, Demikhov was surprised by the words of the driver changing a tyre (4) use primitive anticoagulation available at that time (probably after his car had driven over a nail—he said that a car can be fixed synanthrin), simply by replacing a broken detail. Perhaps it was exactly then that (5) prime machine pumps with physiological saline, and Volodya thought, animals can also be cured by changing body parts. (6) connect his device to blood vessels in only 5–6 min. Soon after his mother caught him with a knife in his hand trying to open the family puppy’s chest to see how the heart works. In 1931 after graduating from a local school 15-year-old Vladimir started to work as a mechanic at the Stalingrad tractor factory. That experience and the skills he learnt laterbecamecrucialforhiswork.In 1934 he entered the Biology Faculty of the Voronezh State University and very soon surprised his teachers and friends—being just a 4th year student he independently constructed the first in history, implantable apparatus, which was able to maintain the circulation in a dog with an excised heart for as long as 5.5 h. The device consisted of two adjacent diaphragm pumps working as two cardiac ventricles and its size was almost identical to that of the native dog’s heart. Two venous cannulae were connected to the atria and two arterial cannulae were connected to the aorta and the pulmonary artery. This work was published in the University student’s newspaper on 19 April 1938 and then presented in May 1938 with great success: ‘A quite interesting report followed by a common approval from the audience was made by comrade Demikhov, a 4th grade honour student specializing in animal genetics. His work is focused on the problem of artificial circulation. Com. Demikhov invented a very orig- inal device to replace the native heart and personally constructed it... The protocol of 24 March sates that: At 18:15 h the death of a Figure 1 Demikhov’s drawing of his first artificial heart. dog caused by cardiac arrest was confirmed...Twelve minutes later

Downloaded from https://academic.oup.com/eurheartj/article-abstract/38/46/3406/4706202 by guest on 08 December 2017 CardioPulse 3407

Figure 3 Demikhov’s excellent records at the Moscow University.

Figure 2 Vladimir Demikhov, student of the Moscow University in 1938. blood, and is a neutral organ, living on the recipient’s blood’. This led him to perform successful intrathoracic heterotopic transplantations of the heart, the lung, and the heart-lung complex—for the first time And what is even more surprising—already then, in 1937, in higher animals. Demikhov predicted that similar devices would be used in future to As a result of performing many procedures survival outcomes keep donors alive, aiming to preserve their organs for transplantation. were improving and a dog operated on 30 June 1946 lived for almost But as often happens, the great value and possible practical implica- 10 h after the heart-. Following further modifica- tions of his invention were not appreciated at that time. And neither tions of his technique experimental animals survived for as long as later on. 30 days after intrathoracic transplantation of both lungs. In 1938, Demikhov transferred from Voronezh to Moscow to con- After successful liver transplantations in 1948 Demikhov reiniti- tinue his studies at the Biology Faculty of Moscow University. In the ated his heart transplantation program and in 1951 he was the first to capital he faced his first challenge: the University required all new stu- successfully perform an isolated orthotopic heart transplantation in a dents to submit a self-photograph in a white shirt with a tie. dog. By improving his technique between 1951 and 1955 he was able Demikhov not only had never owned a white shirt or tie he did not to achieve longer animal survival periods (up to 15 h). And again, all even have the money to buy them! The problem was resolved by procedures were done without cardiopulmonary bypass or hypo- drawing the required garment onto Vladimir’s picture (Figure 2). This thermia. His exceptional dexterity and his original technique of organ young man without a rouble in his pocket would one day change the preservation during transfer were keys to his success. world. On 29 July 1953, Demikhov started experiments with bypassing In August 1940, Vladimir Demikhov graduated with honours from the coronary arteries. He performed end-to-end anastomosis of the the Lomonosov (Figure 3) and very soon he left internal thoracic artery to the left coronary artery using his origi- was conscripted into military service and became a soldier of the Red nal modification of Payr’s technique with a sutureless connection of a Army. Then, in June 1941 the War started. Demikhov was called to smaller vessel to a larger one with a metal ring. Four dogs survived the front as a pathologist and a forensic expert even though he did for as long as 2 years, in all of them and anastomosis patency not have a medical degree. He was in Berlin when in May 1945 the were documented. All interventions were performed without cardi- war against Germany was over, but then the declared opulmonary bypass, defibrillator, proper anticoagulation, surgical war on and he was sent from Berlin to Harbin, . Only at microscopes, or specific instruments. The dog operated on 1 August the end of 1945 was he able to return home having received several 1953 survived for 7 years (Figures 4–6). medals and an order of decoration for his service. On 24 September 1954 at the meeting of the Moscow Surgical His position as an assistant in Department of Physiology of the Society Demikhov stated ‘The laboratory is Lomonosov Moscow State University gave him many opportunities conducting experiments of heart transplantation in mammals to for experimental work. He started with transplanting into the achieve a goal of life prolongation in patients with severe and irrever- inguinal region of cats. These resembled the experiments of Alexis sible damage of this vitally important organ’, then he added ‘Since the Carrel who implanted a puppy’s heart into the neck of a dog in 1905 mortality due to coronarosclerosis is very high, the surgical method and was awarded the Nobel Prize in Physiology and Medicine in 1912 of treating coronary insufficiency by connecting arteria mammaria to ‘in recognition of his work on vascular suture and the transplantation the native coronary artery below the lesion is very physiological, of blood vessels and organs’. However, Demikhov made an interest- experimentally proven and can be widely used in the Soviet health- ing observation ‘because of its anatomical and physiological features care’. But at that time almost everyone regarded Demikhov’s experi- the heart can only function actively when it is transplanted into the mental work as quackery and eccentric. Inspired by Demikhov’s thorax... If it is transplanted to the vessels of the neck or into the ideas, in the early 1960s Vasiliy Kolesov performed his own experi- inguinal region it cannot take an active part in the movement of the ments and then started clinical interventions with grafting of the left

Downloaded from https://academic.oup.com/eurheartj/article-abstract/38/46/3406/4706202 by guest on 08 December 2017 3408 CardioPulse

But Demikhov’s life was not easy, he could not find his place under the sun and had to change his positions several times—from 1947 to 1955 he worked in the Institute of Surgery in Moscow, from 1955 to 1960 in the Sechenov First Moscow Medical Institute and from 1960 to 1986 in the Sklifosovskiy Institute of Emergency Medicine. The Ministry of Health of the Soviet Union, the Minister himself and many important people in medicine were constantly declaring Demikhov’s experiments unethical and were criticising his work and closing his laboratory. Due to the Cold War his experiments were almost unknown for quite a long time as it was very difficult for Demikhov to publish results in foreign scientific journals and vice versa, Western scientists and doctors were almost unable to access or read articles in Russian. The same applied to his very limited ability to travel abroad and present his results to foreign colleagues. But he was occasionally vis- Figure 4 Demikhov’s drawing of the coronary artery bypass ited by foreign journalists and celebrities such as, the brother of surgery. President Richard Nixon and Eleanor Roosevelt, wife of a previous American President. In his 1959 interview to The New York Times, he stated that he was ready to transplant a leg and a heart in a human patient (Figure 7). However, the Iron Curtain kept all his research confined to the Soviet Union. But in May of 1958 even this barrier fell when Demikhov was allowed to demonstrate his experimental transplanta- tions in Leipzig, , followed by great international recog- nition. During his second visit to East Germany in December 1958 to January 1959 Demikhov performed several heart transplantation procedures in dogs (Figure 8). In September of 1959, he participated in the XVIII Congress of the International Society of Surgery and the IV Congress of the International Cardio-Vascular Society that were simultaneously held in Munich. The requirement for him was that he would not make any public announcements there. But he decided to present his transplan- Figure 5 The dog ‘Doga’ 7 years after end-to-end anastomosis of tation results and immediately his behaviour was considered as ‘polit- left ITA to LCA. ically incorrect and dangerous’. Demikhov was accused of disclosing national secrets, only his worldwide recognition (and his legendary cousin—General Sergey Shtemenko) prevented his arrest. On 24 February 1954, Demikhov performed probably his most controversial experimental operation—he transplanted a head (more precisely—an upper half of the body) of a dog on to another larger dog (Figure 9). The first transplantations were not very success- ful, but with time and experience the maximal survival of animals reached 29 days. News of this experiment became far more famous than Demikhov’s earlier works. The operation raised important ethi- cal issues and serious discussions on acceptance of such procedures and their true medical need. In 1960, Demikhov published his book ‘Experimental Transplantation of Vital Organs’ where the word ‘transplantology’ was used for the first time in the literature. It was the world’s first monograph in the new and unknown area of medicine and biology Figure 6 Contrast angiography of the anastomosis 7 years after with thorough description of different approaches and surgical tech- surgery. niques. In his book, Demikhov wrote that ‘Such experiments on heart and lung replacement were the first, not only in our laboratory, but in the history of science. Before this time, the possibility of heart and internal mammary artery to the left anterior descending coronary lung replacement in warm-blooded animals was not even consider- artery. From 25 February 1964 through 9 May 1967 Kolesov’s ed’. Soon afterwards the book was translated and published in New Department of Surgery in Leningrad was the first and only place in York (1962), Berlin (1963), and Madrid (1967) and for a long time the world where such procedures were performed routinely. was the only monograph in the field of transplantation of organs and

Downloaded from https://academic.oup.com/eurheartj/article-abstract/38/46/3406/4706202 by guest on 08 December 2017 CardioPulse 3409

Figure 8 Demikhov performing experimental surgery in Leipzig.

Figure 9 The dog with two heads.

Figure 7 Article in The New York Times.

Russians can do, we can do, too’ he reproduced the experiment by transplanting the head of a dog onto another dog on that same after- tissues. It became the ‘bible’ for many surgeons and biologists who noon. The dog survived for several days, but animal-rights protectors were following his steps. and medical students started a campaign again for what they consid- A scientific career for Demikhov was also not easy, in 1963 he ered unacceptable experiments’. finally received a scientific degree, but not in medicine. After many Later Barnard wrote a letter to the Minister of Health of the attempts and painful experiences his dissertation was accepted at the Soviet Union requesting permission to visit Demikhov’s laboratory Biology Faculty of Lomonosov Moscow State University. Surprisingly, to learn about organ transplantation. At that time there was no offi- during the public defence of his results Demikhov received extraordi- cial contact between the Soviet Union and South Africa, so Barnard nary positive support, and instead of being awarded the scientific was denied his request. He then visited Moscow as a regular tourist degree of a Candidate of sciences, the dissertation council decided to and spent some time with Demikhov in his lab. Those experiments award him the highest degree of Doctor of biological sciences. definitely convinced Barnard that human heart transplantation was In his book ‘Landmarks in Cardiac Surgery’ Stephen Westaby possible. writes, ‘in 1962, when an article on Demikhov’s head transplantations On 3 December 1967, at the Groote Schuur Hospital in Cape was published in the Cape Argos newspaper, Doctor Christiaan Town, performed the first successful transplanta- Barnard, a young cardiac surgeon at the Groote Schuur Hospital, tion of a human heart from a person who had just died from a head became very excited after reading it. With words ‘anything those injury.

Downloaded from https://academic.oup.com/eurheartj/article-abstract/38/46/3406/4706202 by guest on 08 December 2017 3410 CardioPulse

Leipzig University (Germany). In April 1989, during its annual meeting in Munich the International Society for Heart and Lung Transplantation was ‘Privileged to present the first Pioneer Award to Professor Demikhov of the Soviet Union for his leadership role in the development of intrathoracic transplantation and the use of artificial hearts’. Demikhov was able to attend the ceremony himself accom- panied by his daughter Olga and received the award and a very warm reception from his colleagues (Figure 10). The whole world recog- nized his outstanding input in the development of organ transplanta- tion and awarded him highest honours, but it was in his own country where Demikhov was forgotten and neglected. Only in 1998 was he awarded the 3rd class Order of Merit for the Fatherland. Vladimir Demikhov married in August 1946 and he with his wife Lia lived together for almost 52 years. Their daughter Olga Demikhov was born on 16 July 1947. In the early 1950s, he brought his mother to live with them, and until 1972 when his mother died the four of them lived in two tiny rooms. He died in his small apart- ment on 22 November 1998. Clarence Walton Lillehei, one of the world’s foremost cardiac sur- geons, once said ‘Some see things as they are and ask—Why change? Figure 10 presents the first ‘Pioneer Award’ to Others dream of things that never were and ask—Why not!’ This is Vladimir Demikhov. all we can say about the brilliant life of Vladimir Demikhov.

Simon Matskeplishvili MD PhD In December 1996, almost 35 years later, Christiaan Barnard par- Professor of cardiology Member of the Russian Academy of Science ticipated in the Third Russian Congress of Cardiovascular Surgery Deputy Director for Science and Research, Moscow University Hospital, Lomonosov Moscow State University and began his address with: ‘If not for the basement of the Executive Board Member of the Russian Society of Cardiology Sklifosovsky Institute I would never have been be able to do that. [email protected] Vladimir Demikhov is the founder of transplantology...’. In 1997 in his letter to Dr Igor E. Konstantinov regarding the importance of Conflict of interest: none declared. Demikhov’s experiments Barnard wrote ‘He was certainly a remark- able man, having done all the research before extracorporeal circula- References tion. I have always maintained that if there is a father of heart and lung References are available as supplementary material at European Heart transplantation then Demikhov certainly deserves this title’. Journal online. Demikhov was awarded honorary memberships of the Royal Scientific Society of Uppsala (Sweden), the Mayo Clinic (USA), and

The Lomonosov Moscow State University was established in 1755 by decree of Empress Elizabeth of Russia on the initiative of the great Russian scientist and polymath Mikhail Lomonosov. The first three Faculty’s were Philosophy, Law, and Medicine. Many famous people grad- uated from the medical faculty e.g. Anton Chekhov, who practiced as a physician throughout most of his literary career. In the 1930s, when the Soviet Union was preparing for war, many physicians were required for the army and it was decided to separate the Faculty’s of Medicine from the universities and for them to become autonomous medical institutes. The same happened to the medical faculty of Moscow University which then became the I.M. Sechenov First Moscow Medical Institute. Only in 1992 did medical education ‘return’ to the University when the Medical Faculty was re-established at Moscow University. Later, Michael DeBakey ‘convinced’ the Rector that the University with a Medical Faculty cannot exist without a medical centre (hospital), so the new Hospital (clinic) was built in 2012. It is the first ‘classic’ University Hospital in post-Soviet Russia. In December 2017 the Lomonosov University will be celebrating three anniversaries—260 years of medical education, 25 years as a Medical Faculty, and 5 years for the University Hospital. The Dean of the Medical Faculty and the Director of the Hospital suggested naming it after Vladimir Demikhov, as a tribute to his outstanding role in medicine. The decision has not yet been made, but we are hoping that it will be so.

Simon Matskeplishvili MD PhD

Downloaded from https://academic.oup.com/eurheartj/article-abstract/38/46/3406/4706202 by guest on 08 December 2017