For the purpose of providing brain circulation for these models, from 1922 to 1924 Bryukhonenko designed and constructed the first automated blood circulation device.2 The diagram of the device is shown in Figure 4. It consisted of two closed loops of circulation, which was the main differentiating feature in comparison to older extracorporeal circulation devices. Technology in those days did not allow the use of plastic or metal as blood–machine interface; therefore, blood interface was created from glass, whereas pump lines were made of rubber. The circuits were powered by two pumps brought into motion by an electric motor.
The second unique characteristic of his device was autoregulation of pump rate to ensure stable blood pressure in the system independent of blood pressure in the canine brain. Because of this feature, Bryukhonenko called his device “Autojector” (a portmanteau of “auto” and “injector”). At the initial stage Bryukhonenko used sodium citrate for anticoagulation and oxygen bubbles for oxygenation. However, the high doses of sodium citrate required for adequate anticoagulation were toxic for the animal, and oxygen bubbles were not sufficient to oxygenate the amount of blood needed to prime the device. As a result Bryukhonenko began to isolate lungs from the same donor canine that was exsanguinated in order to prime the pump and also use the isolated lungs for oxygenation. He simultaneously studied anticoagulant properties of various chemicals and eventually identified cellulose-based direct anticoagulants, which he named “Synanthrins.” They were first synthetized in 1935 at the Moscow Chemical-Pharmaceutical Science Institute under his guidance and utilized in his later experiments.4 Unfortunately, little is known about his methods for eliminating air bubbles in the oxygenator.
In 1925, Bryukhonenko joined with Sergei Tchetchulin, an apprentice of the famous physiologist Ivan Pavlov, who was interested in neurohumoral regulation by higher nervous activity and who helped Bryukhonenko to improve the Autojector’s design. Bryukhonenko and Tchetchulin first demonstrated the Autojector at the 2nd All-Union Meeting of Pathologists in September 1925. Then in May 1926, in an experiment at the 2nd All-Union Meeting of Physiologists, for the first time they demonstrated revival of a canine head.5 This experiment was essentially the first demonstration of a means to support life of a brain using oxygenated blood perfusion. Further publication about this method is followed in 1928 and 1929.6,7
EXPERIMENTAL MODEL FOR TOTAL BODY PERFUSION
By the end of 1926, Bryukhonenko was able to improve the Autojector’s pump power and increase its capacity, allowing him to develop his third experimental model: perfusing the entire canine body8,9 (Figure 5).
The experiment consisted of following steps:
- In the first stage, the carotid artery and jugular vein of a sedated animal were cannulated and connected to the Autojector with arterial and venous pressures automatically maintained at set levels. At this point the animal’s native heart was working in parallel with the pump that Bryukhonenko named “parallel circulation.”
- Next the experimenter would dissect out the animal’s heart and squeeze it manually, effectively preventing it from filling. At this point, the Autojector was turned off, and the experimenter waited until cardiac fibrillation and arrest and disappearance of respiratory motion. The time varied from 2 to 8 minutes.
- Next the Autojector was started again, restoring blood perfusion to the animal.
- At a later time respiratory motion and heart rhythm would recover, reverting back to the parallel circulation.
- Once respiratory and hemodynamic parameters returned to their original state, the Autojector was disconnected. From November 1926 to February 1927, a total of eight of these experiments were performed.
Surgical assistance during these experiments was provided by Nikolay Terebinsky, one of few surgeons in the Soviet Union who had experimented on cardiac procedures and was familiar with cardiac anatomy. Although the details of his assistance are not known, it would have included cannulation, thoracotomy, pericardiotomy, cardiac arrest, pericardiorrhaphy, and closure of the chest wall.
Nine conclusions were made from these experiments. Of note, the first eight conclusions were purely physiologic concerning canine revival after cardiac arrest and providing life support until recovery of cardiac and respiratory functions. Only the ninth conclusion stated: “solving the problems of artificial circulation of the entire warm-blooded organism brings on performing surgery on a heart as a next challenge.” Interestingly, for many years Bryukhonenko never tried to apply his methodology to cardiac surgery; therefore, we presume that it was Terebinsky who appreciated the importance of the Autojector for cardiac procedures and was responsible for the ninth conclusion. Indeed, from 1929 to 1937, Terebinsky performed valve interventions on beating and fibrillating hearts utilizing the Autojector.10 Of note, Bryukhonenko hypothesized the use of the Autojector for critical conditions that required unloading the sick heart to allow the patient time to recover. However, to the best of our knowledge, he never clinically attempted to use his device to rescue a patient out of severe heart failure.
Further demonstrations of Bryukhonenko’s experiments at the 1928 and 1930 Soviet All-Union Meeting of Physiologists included not only revival of a canine head but also the entire canine organism. The same experiments were again demonstrated at the 15th International Physiology Congress in Moscow. These demonstrations deeply impressed Soviet leadership and catapulted Bryukhonenko to fame, which resulted in immediate promotion to director of the Research Institute of Experimental Physiology and Therapy including 150 employees. From 1929 to 1930 Bryukhonenko obtained patents for the Autojector in Germany, UK, and France. In 1937, Bryukhonenko’s Autojector may have served as an inspiration for Vladimir Demikhov’s development of the first experimentally implanted total artificial heart.11
EXPERIMENTS ON HUMAN CADAVERS
After further perfecting his experiments to achieve recovery after 20 minutes of cardiac and respiratory arrest, Bryukhonenko requested permission from the Soviet Government to experiment on human cadavers. At that time he already had improved the Autojector design with a bubble oxygenator called “Aerator” (an aeration device) developed by Vladimir Yankovsky under the guidance of Bryukhonenko (Figure 6). He was immediately granted such permission; however, despite initial enthusiasm,12 Bryukhonenko was unable to produce positive results, which caused him to fall out of favor with Soviet leadership.
During World War II, his facility was repurposed to produce military supplies and anticoagulants. In 1944, Bryukhonenko’s institute was reorganized into a small laboratory and transferred to Sklifosovsky Institute of Emergency Care, where he continued his experiments with the revival of human cadavers and further advanced his Autojector (Figure 7). In 1952, Bryukhonenko reported data on his unsuccessful attempts at reviving 120 deceased patients delivered to his laboratory within 30–60 minutes after diagnosis of death by an emergency physician.13 Such persistence could only be explained by his deep belief that the capacity of neurologic recovery was much greater than what was presumed at that time—that prolonged brain anoxia does not lead to death but merely to deep recession of its function and that lack of activity of neural centers does not equal proof of death.
DEVELOPMENT OF FIRST CLINICALLY USED CARDIOPULMONARY BYPASS MACHINE
In the early 1950s, Soviet thoracic surgeon Alexander Bakulev put forth a plan to develop a Soviet cardiopulmonary bypass machine to perform cardiac operations. At that time Bryukhonenko, who was located at Research Institute of Medical Devices and Instruments, took on this task but could not accomplish it successfully. Ironically, another laboratory at the same institution, but without Bryukhonenko’s involvement, succeeded in creating the first Soviet clinically usable cardiopulmonary bypass (CPB) machine. The device, called AIK (an initialism for “apparat iskusstvennogo krovoobrashchenia” [apparatus for artificial blood circulation]) only borrowed diaphragmatic pumps and bubble oxygenator from the Autojector. In late 1957, the first human open heart operation was performed by Alexander Vishnevsky. In 1958, when Bryukhonenko was invited to join the Institute of Pathology of Blood Circulation in Novosibirsk, he made two Autojectors to carry out the heart operations on children and adults (Figure 7B). Unfortunately, because of Bryukhonenko’s illness, he could not move to Novosibirsk and these devices were never used clinically.
Bryukhonenko died in 1960 from rectal cancer. That same year the British Medical Journal published an article about Bryukhonenko and his Autojector, indicating that Bryukhonenko never received enough recognition and credit for his pioneering work.14 In 1965, posthumously, Bryukhonenko received the Lenin Prize—the highest scientific award in the Soviet Union—for laying out scientific foundations and advancing understanding of artificial blood circulation.
In the 1930s, the ideas of life prolongation and even “eternal” life were very fashionable in the Soviet Union, and presumably encouraged by Joseph Stalin. We believe this idea of the possibility of revival greatly inspired and motivated Bryukhonenko so that he continued this line of work for the rest of his career. He not only developed the idea for the Autojector but also was directly involved with its actual design and construction.
An interesting parallel can be made here with Alexis Carrel, who was fascinated with the idea of permanent life of tissues outside of the organism.15 From 1935 to 1939, he performed single-organ perfusion experiments using a perfusion pump he developed in collaboration with Charles A. Lindbergh with the goal to allow extracorporeal survival of organs.16 Other pioneers in the field included Staub and Basel in Switzerland and Gibbon in the United States. Staub published his results in 1931.17 Bryukhonenko developed his methodology from 1922 to 1924 and by 1926 he had already advanced his methodology to total body perfusion, although Staub did not begin experimenting until after 1927. It is important to make a comparison to Gibbon’s 1937 invention of the cardiopulmonary bypass machine,18 which became the foundation of the modern CPBs used worldwide. Gibbon’s original device was created not for substituting the heart but rather with the lung function in mind (pulmonary embolism). For Bryukhonenko pulmonary function/oxygenation was secondary, although for Gibbon the mechanical pump was an extension of his artificial oxygenator.
With his accomplishments, Bryukhonenko deserved credit for the creation and first successful experimental use of a heart-lung machine in the 1920s.19 Although the importance of this innovation to cardiac surgery was not realized right away, the Autojector was the first device experimentally used, and its clinical use was formulated for supporting the whole body during cardiac arrest. From this standpoint, the Autojector can be considered the first experimental extracorporeal life support. Eventually, Terebinsky applied Bryukhonenko’s methodology to open heart experiments. With his work, Bryukhonenko, along with Terebinsky, laid the groundwork for developing cardiac surgery in the Soviet Union.
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Keywords:Copyright © 2018 by the American Society for Artificial Internal Organs
autojector; history of mechanical circulatory support; Bryukhonenko; Soviet Union