Almost every day we see a wheeled machine whirring in a specially equipped operation theatre where several cardiac procedures are performed requiring a variable time of cessation of the activity of the patient's heart and lung. The recovery is almost 100% and this is an example of the modern-day heart surgery involving a Heart-Lung machine. Well, the story of its development and its use for the successful open-heart procedure is not simple. Many things were needed and it took 26 years of dedicated research to reach a stage where it could be used in cats and other animals used for laboratory research only. Without the scope for a human trial, the machine had to be readied in such a manner to be capable of foolproof use. Only a success had the chance for continued use in humans.
As a surgeon one needs awareness of some simple facts. The alveoli, where the actual gas exchange occurs, is an outpouching at the end of a terminal bronchiole or respiratory passage. There is a single cell lining, one surface facing the pulmonary capillary and the other the environmental gas. This is where the actual exchange or giving up of oxygen in lieu of carbon dioxide occurs. The gases then pass through this semipermeable cellular barrier into the bloodstream and oxygen is delivered to the tissue in need. If the concentration of inspired and expired gases were measured, only a difference of 5% favoring oxygen in the inspired air would have been seen. So the human race can survive 21-23% of oxygen in environmental air and the requirement for a 70 kg human being is roughly 5-6ml at 28* Celsius, the alveolar gas exchange surface being equivalent to approximately 50 square meters.
When John Heysham Gibbon plunged into the project, the enormity of the task was beyond comprehension, and problems along the line had to be dealt with accordingly. The simple realization is that visual confirmation and estimation along with cognitive assessment are necessary for such a surgery. The only thing in his support was this was a happening period and even though he did not receive any encouragement from his teachers, seniors, or peer, his wife, Mary Gibbon, remained steadfast in her support and did the bulk of the work in setting up the gradually developing gear. John Gibbon had to suffer the ordeal of watching a pulmonary embolism patient die. From that experience, he kept on thinking about whether a device could be developed which would help one to extract an embolus from the pulmonary tree in a quite blood-free heart. He was given reluctant permission by, Dr. Edward Churchill, the then teacher whose pulmonary embolism patient he watched die. It was at this stage, that oxygenation of the blood, its transport to organs other than the heart, free of air bubbles, and the ability to work quickly in a quiet environment was the main goal. By the late 1930s, James MacLean a student, working in Howell’s laboratory had not only discovered Heparin, but had been able to draw the interest of Charles Best, of insulin fame. He together with Gordon Murray introduced heparin in clinical practice. Till heparin, the problem with clotting had only been solved partially. Two French researchers, Provost and Dumas, showed that beating blood for some time with a whisk separated fibrin which was a clot-promoting protein. However, this was not practical and the discovery of heparin solved several problems. Designing the pump was easier. There was a pump in the milk industry that was capable of positive displacement without any contact with the fluid in a propelling fluid. The patent was in the name of Porter and Bradley (1855). Allen made certain small modifications for rapid blood transfusion and operation with a hand-crank. At least 26 more modifications and patents followed. By the early 1930s, when Gibbon was deeply working with the goal of a Heart-Lung machine, Debakey suggested this pump. Though Debakey’s name is often mentioned as the pump inventor, the industrial roller pump had been modified many times to suit medical practice. Gibbon incorporated this pump with an oxygenator he was trying to build. He had to remember that the pump had to be powerful enough to propel blood to every nook and corner of the body and at the same time gentle so as not to destroy the fragile blood cells, mainly RBCs.
Since its inception, surgeons were on the lookout for a device or a way to venture into cardiac surgery. In 1896 only with Rehn’s achievement, they came to know that cardiac surgery was possible and the heart can withstand a surgical insult. However, the research was older. The oldest reference to this unique problem is as early as 1666 when Robert Hooke suggested that oxygenation of blood requires mere exposure to an environment where the concentration of oxygen is higher. 2 centuries later Julien Legallois, a professional vivisectionist, proposed re-animation after death by re-circulation. He showed that blood differed physically as well in contents after a pass through an organ. Some gory experiments during the post-French revolution period need to be mentioned. Legallois’ student Brown-Sequard’s name comes first. In 1850 he severed a dog’s head and injected whisked blood into the cut vessels. He claimed to have seen a brief movement of the eyes and muzzle and deduced a brief “resurrection of life”, the possibility of which was hypothesized by Legallois in the early 19th century. Brown-Sequard went further a year later and observed setting in of rigor mortis, which took more than 12 hours, in guillotine decapitated bodies. With his associates, he severed the arm of the dead person. Next, he injected about a 3rd of a pint of fresh whisked and gauze filtered blood for half an hour into the dead arm. After half an hour he noticed softening of the arm with the regaining of the contractile quality. Though he was vindicated in his observations, a method for continuous injection was not available at that time. Oxygenation of blood was another issue. In 1868, Ludwig and Schmidt put dark blood in a balloon filled with oxygen, shook it, and injected it into isolated livers and lungs. The liver continued secreting bile and lung gases showed increased carbon dioxide concentration suggesting revitalization of metabolism. Another German, von Schroder (1882) demonstrated oxygenation of blood by bubbling oxygen through a column of blood. However, the foam produced, as a result, made the blood unusable. In 1885, the Austrian physiologists Max von Frey and Max Gruber came close to constructing the fully functional Heart-Lung machine of that time. They carried out experiments on the kidneys and hind legs of killed dogs in the laboratory. They did not perform any human studies. Experiments with and constructing an apparatus for perfusion were a fashion of that time. Even the Nobel laureate Alexis Carrel collaborated with the aviation pioneer, Charles Lindberg. Their ventures went as far back as the early 20th century.
Behind the iron curtain, a Russian maverick Sergei Surgeyevitch Brukhonenko was experimenting with his “Autojector”. The instrument used two pumps for simulating the action of the heart and the first version used a recently killed dog lung, inflated and deflated manually with a bellow. He was mainly known for his experiments of beheading mainly dogs and trying to keep the beheaded dog alive by connecting it to the “Autojector”. His feats are documented in the film 'Experiments in the Revival of Organisms’. Another brilliant Soviet surgeon was Demikhov. His feats are mainly remembered for paving the way for transplant surgery. Both did experiments on beheaded dogs and the Western media used the terms gory and macabre. However, the ideas and novel methods inspired many and helped in further development when news about these feats came out.
Gibbon’s idea was simple and the idea of the stationary screen oxygenator was taken from one constructed by the American physiologist, Donald Hooker, later famous as the uncle of the movie star Katherine Hepburn. Gibbon managed to integrate the mechanical pump with the stationary screen oxygenator. The experiment demanded his hands were free and that he could use them for clamping the various vessels. He realized that his oxygenator was not adequate. So cats were the obvious choice. The world wars were major events, not only enriching the surgeons with knowledge by teaching them to handle gory situations, but also thwarting the pioneers in their quest for glory. Rather a breather was given and the researchers got the time to think. Almost everybody, on both sides of the curtain, enrolled in the war effort, and most had heroic contributions. Hypothermia was investigated extensively by Bigelow and Shumway’s paper laid the foundation. Two Italian researchers, Dogliotti and Ciocatto, even we’re able to combine the effects of hypothermia with Gibbon’s method of open-heart surgery. These observations were in agreement with Ite Boerema’s suggestion of deep hypothermia with the saturation of tissues with hyperbaric oxygen. The ‘Azygos flow principle’ was another important observation at that time. That the brain and other vital organs could withstand only 10% of total cardiac flow, helped researchers to think about scaling down ideas. Gibbon was fortunate to have the usage of heparin as the anticoagulant. By 1935-1936 he and Mary Gibbon had managed to succeed in keeping a cat alive for 20 minutes after totally clamping the pulmonary artery thus interrupting pulmonary blood flow. In 1937, Gibbon came out with a paper in the Archives of Surgery, volume 34, issue 6, about “Artificial maintenance of circulation during experimental occlusion of the pulmonary artery”. By 1939, Gibbon and his wife were able to sustain the life of at least 4 cats. Gibbon presented his results at a surgical conference in Los Angeles. His feat was likened to Jules Verne’s vision of realization of present-day dreams as latter-day realities. Industry pitched in at this juncture and with the involvement of IBM sophistication in machinery was noticed. Gibbon at this time calculated an 8 square meter stationary oxygenator as the optimum requirement for a human subject. The first generation machine was delivered in 1946 and by that time Gibbon was successfully experimenting with dogs. In 1953, with a later generation prototype, Gibbon repaired the first ASD, 18year old Cecelia Bavolek, on direct vision. That he failed in subsequent ventures and enforced a self moratorium is a different story, but the gateway to the open-heart procedure was opened.
Post-script many things happened. Clarence Walton Lillehei was a daring surgeon of that time with a special interest in cardiac surgery. He was undecided about Gibbon’s contraption and adopted the “controlled cross circulation” technique with one parent of the same blood group as the auxiliary support. However, as someone would say, this method had the potential of 200% mortality and even though Lillehei’s results were enviable, there were not many such surgeons who had his dexterity. John Kirklin was at the same time toiling with a Gibbon prototype 90 miles away at Rochester, Mayo clinic. He was disciplined and meticulous. By the same time, Kirklin was having similar success. Lillehei used to visit Mayo clinic and was gradually getting motivated by Kirklin’s technique. He entrusted DeWall of his team to develop a simpler version of the oxygenator and a scheme of the oxygenator with a venous reservoir at the top. The spiral tubing oxygenates blood and gravity eliminated air bubbles at the same time. DeWall’s oxygenator was simple, cheap, and easy to assemble. Along with Lillehei’s surgical dexterity, this oxygenator went a long way to popularizing open-heart surgery. Later Vincent Gott was given the task of replacing the hard shell of the oxygenator with a plastic sheet. Addition of defoaming agents followed and disposable bag oxygenators were desired by all cardiac surgeons.
The evolutionary history of the Heart-Lung machine is replete with events that have some effects on that time. Painstaking research and the effort that went with it are difficult to record. It is very difficult to maintain a chronological timeline and the events were overlapping in many situations. It is said that the Heart-Lung Maxine was discovered twice, once by Max Von Fey and Max Gruber, and the second time by Gibbon. Gibbon’s feat in 1953, will be remembered as he was able to use it successfully for human purposes and opened the path for open-heart surgery.