“We cannot await favors from nature, our mission is to take them from her”
Ivan Michurin, Soviet agronomist and selectioner.1
In the 1930s, the Soviet Union was undergoing rapid industrialization under Joseph Stalin. The fast-paced mechanization era coincided with the widespread Cartesian worldview among Soviet scientists who believed that anything was possible with human influence on nature. This worldview had a crucial influence on Demikhov in his younger years and likely contributed to the origination of his idea to create the world’s first total artificial heart.
Vladimir Demikhov was born on July 18, 1918, in Jaryzhenskaya village, Novoanninsky District of Russian Empire. The area had been inhabited by Cossacks who voluntarily served the Russian Empire by protecting its southern borders. Features of Cossacks—love for freedom, self-confidence, and self-reliance—became defining factors of Demikhov’s character. While obtaining his basic education, he simultaneously worked as a mechanic at a local tractor factory. The manual skills he obtained there, working with metals and building complex constructs, would become crucial for his future work.
In 1934 at age 18, he was accepted at the biology school of Voronezh State University (VSU) through Komsomol. He might have chosen biology because of his early exposure to and love of animals from his childhood in the village and possibly because he would not have been able to enter a much more competitive medical school due to lack of proper preparation.
At VSU, he worked under physiologist Pyotr Nikiforovsky, a former trainee of world-renowned Ivan Pavlov, and acquired a comprehensive knowledge in the field of animal physiology and blood circulation. At that time, Nikiforovsky’s group was working on the central nervous system of mammals, including then-secret experiments in organism revival. Our team discovered that for this latter purpose Nikiforovsky’s group had an early analog of a cardiopulmonary bypass machine called “autojector” that Nikiforovsky had obtained directly from its inventor—renowned Soviet physician, physiologist, and engineer Sergei Bryukhonenko. Demikhov most likely was exposed to this device in Nikiforovsky’s laboratory, where it would have served as an inspiration for his later creation.
In late 1937, 21 year old Demikhov independently constructed the “mechanical heart” in Nikiforovsky’s laboratory and tested it in a dog model in early 1938. According to the VSU newspaper from May 1938,2 after 12 minutes of absent circulation, the dog was implanted with the self-made device, which was brought into motion by an external electric motor. The dog regained signs of life within 16 minutes of reperfusion by the pump (Figure 1):
“A quite interesting announcement, resulting in loud approval from the audience, was made by comrade Demikhov, a 4th grade honor student, in the specialty of animal genetics. His work focused on studying the problem of artificial circulation. Com. Demikhov constructed a very original device meant to replace the native heart. He created it himself in the facilities of VSU and independently initiated experiments in dogs. Com. Demikhov describes in detail the methodology of the experiments and conduct of the operation. The outcome of Demikhov’s persistence is well-defined results documented in the protocol on March 24th: «At 6:15 [PM], the dog’s death was confirmed, caused by shutting down the native heart (by the means of ligation of coronary arteries). Twelve minutes later the heart replacement device was turned on and brought into motion by an electromotor. Within 16 minutes on the device, the dog began demonstrating obvious signs of life (respiratory, ocular, and protective reflexes) up to the point of the most sensitive reflex». Further, com. Demikhov discusses the scientific and practical merits that his work could have upon further development such as studying the problems related to organism death, heart surgery, anabiosis [temporary suspended animation or greatly reduced metabolism], the effect of pharmaceutical drugs on individual systems of a living organism, and so forth.”
It is believed that the device was made with steel pump housing and rubber tubing, and the valves made of rubber flaps. Besides the newspaper article, however, no further information has reached us from those years. Later in his 1959 book, “Heart Transplantation—Is it Possible?,”3 Demikhov provided the first drawing of his creation (Figure 2). His seminal monograph, “Transplantation of Vital Organs in Experiments,”4 outlines further details about his 1938 experiments. The device was constructed in the size of the native heart and consisted of two adjacent diaphragm pumps performing functions of the two cardiac ventricles. It had two venous and two arterial cannulae—the venous cannulae connecting to the atria and the arterial cannulae connecting to the aorta and the main pulmonary artery. The atria were ligated at the ventricular bases, and the ventricles were removed. The device fit in the thoracic cage in place of the native ventricles with the dog’s chest closed. The pump was brought into motion by a rod brought through the chest wall and connected to an external electric motor:
“Given the fact that in native conditions the heart essentially represents a living force pump circulating blood through the entire organism, we came up with an idea to replace the heart with a mechanical device.”
“For this purpose, in 1937 we constructed a compact device the size of the native heart, which consisted of two adjacent membrane pumps performing functions of the two cardiac ventricles.”
“The device was placed in the chest to replace the removed native heart. A cylindrical arm of the device was brought out through the chest wall and put into motion by an electromotor. After externalizing the arm, the chest was fully closed.”
“The chest of the dog was opened under ether anesthesia using mechanical ventilation. The main pulmonary artery and the ascending aorta were dissected from each other in a blunt fashion. A preparation preventing blood coagulation was administered intravenously (supplied by its creator, V.I. Maksimov).”
“Both atria were cannulated through the appendages using the wide venous cannulae of the device. (The device was primed with Lactated Ringer’s solution.) The cannulae were secured with thick ligatures around the atrial appendages.”
“An elastic clamp was placed on the ascending aorta and the main pulmonary artery at their branching points distally from which the cannulae of the device were placed and secured.”
“Arterial cannulation and the switch of the circulation to the mechanical device were performed as fast as possible, within 5–6 minutes, to prevent prolonged disruption of blood supply to the brain. Both atria were tightly ligated at the ventricular bases, after which both ventricles were removed. Once the device was turned on, the blood moved from the right atrium through its appendage and the venous cannula into the right part of the device from where it was forced into the lungs. From the left atrium, the blood moved through the venous cannula to the left part of the device and further forced into systemic circulation. Three experiments were conducted at that time , with five more experiments in 1958.”
“With maintenance of the dog’s artificial circulation during 5 hours and 30 minutes (without the native heart), all signs of life were observed.”
“For this reason we can hypothesize that supporting the life of an organism, revived within minutes after its death (with irreversible damage to the higher brain areas) using the above described or other methods, can be considered a certain means of “physiologic conservation” of tissues and organs for transplantation in a human.”
“Achieving the ability to support the life of a ‘revived organism’ for a certain time makes it possible to transplant any organ of such ‘revived organisms’ (with consideration of immunologic factors), as well as to investigate a series of questions in experimental biology and medicine.”
Demikhov conducted three experiments in 1938. As he indicated in 1950 and 1959, these animals were supported for 2.5 hours. In the above source, he indicated 5.5 hours; however, with this larger number, he likely was referring to his later experiments conducted in Moscow using more sophisticated laboratory equipment, allowing him to sustain the animals’ lives longer.
After Demikhov’s initial experiments and his report about the results at the students’ scientific conference, Bryukhonenko later reported about this device at the regional medical conference in Voronezh.4 After the 1938 experiments, Demikhov, most likely encouraged by Bryukhonenko, transferred to Moscow to continue his research. Unfortunately, soon after Demikhov’s transfer, his first teacher Nikiforovsky was arrested in relation to his prerevolutionary background, a very common event in the 1930s under Joseph Stalin.
Demikhov’s experiments took a lengthy hiatus during World War II (1939–1945), when he served his country as a pathologist in the Red Army. After the war, he eventually resumed his work on the artificial heart in Moscow where he would further refine it (Figure 3). However, at this point, he was primarily focused on heart and lung transplantation, resulting in the series of pioneering experiments that the senior author of this paper (L.B.) had the privilege to witness.
Given the striking similarity between Demikhov’s mechanical heart and Bryukhonenko’s Autojector (Figure 4), Demikhov must have created his original prototype with the autojector in mind (and perhaps even in front of his eyes). Despite these similarities, one principal difference is that the autojector was an extracorporeal device, whereas the fourth year student’s mechanical heart was implantable.
Although specifics of Demikhov’s anticoagulation strategy are not available, it is widely believed that he used synanthrin,5 a cellulose-derived direct anticoagulant first synthetized in 1935 at the Moscow Chemical-Pharmaceutical Science Institute under Bryukhonenko.
Although Bryukhonenko was not involved in Demikhov’s design of the mechanical heart and his initial experiments, the brilliant student must have attracted Bryukhonenko’s attention with his results. Soon after his initial experiments, Demikhov unexpectedly requested a transfer to Moscow for further study. His handwritten request mentioned the importance of his work. Furthermore, even though Demikhov’s request for transfer was declined because of the absence of open positions at Moscow State University, he nonetheless managed to transfer to Moscow in 1938 and continue his studies there. Demikhov had no connections whatsoever to arrange such a transfer, which could be indirect evidence of Bryukhonenko’s intervention to bring the talented and promising young man to Moscow. We believe that Demikhov could have been encouraged by Bryukhonenko to write the letter in the first place. Demikhov and Bryukhonenko would eventually become close friends and have a productive collaboration in Moscow.
Although Demikhov never really abandoned work on his artificial heart and continued to refine it in Moscow, the details of his work remain unknown in part because of the fact that his pioneering experiments in organ transplantation overshadowed the rest of his work. At that time, Demikhov merely viewed the artificial heart as a means to achieve heart transplantation.
Demikhov’s 1960 book “Transplantation of Vital Organs in the Experiment,” from which some of information was taken for this article, was translated into English and published by Plenum Press, New York, in 1962.6 The book has long been a bibliographic rarity. Unfortunately, no readily available English text related to his early work on the artificial heart is known to us to refer the reader for further information.
Besides creating the world’s first implantable total artificial heart, Demikhov’s achievements as a 21 year old, fourth year biology student at a provincial institution remain astonishing in several other ways: his expertise in anesthetic, anticoagulation (a very rare expertise at that time), pump circuit priming, the technical mastery of implanting the device in 5–6 minutes, and the engineering skills to run and troubleshoot the device that he created. Demikhov’s name has inspired and will continue to inspire generations of scientists and researchers in our field and beyond.