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CHAPTER 2: BIRTH OF AN IDEA AND THE DEVELOPMENT OF CARDIOPULMONARY BYPASS

HARRIS B. SHUMACKER, JR.

H.B. Shumacker, Jr: Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.

A PATIENT IN DISTRESS

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It was midafternoon on October 3, 1930 and a patient lay dying at the Massachusetts General Hospital in Boston. For 2 weeks her convalescence from an uncomplicated cholecystectomy had been uneventful. Moments before, however, returning to bed after a wheelchair trip to the toilet, she suddenly developed discomfort in her right chest, and almost immediately the discomfort gave way to sharp pain. Dr. Edward Churchill, who saw her at once in consultation, found her frightened, pale, cyanotic, cold, and moist. He believed that the diagnosis of massive pulmonary embolism was evident, and at his suggestion she was moved in her bed to the operating room where a pulmonary embolectomy could be undertaken as soon as a decision to proceed was made. John H. Gibbon, Jr. was assigned the task of watching the patient and monitoring her vital signs.

Her pulse, blood pressure, and respiration were determined and recorded at frequent intervals. Afternoon and night passed. Finally, at 8:00 a.m. the next morning, her condition worsened further, respirations ceased, a pulse could not be felt, and she lost consciousness. Within minutes, Churchill had opened the chest, made an incision in the pulmonary artery, and extracted several large clots. It was to no avail; the patient could not be revived. Gibbon told of this experience in remarks made in 1972 and published posthumously 6 years later (1):

A correct diagnosis of massive pulmonary embolism was made and Dr. Churchill had the patient moved to the operating room where she could be continuously observed and operated upon immediately should her condition become critical.

My job in the operating room was to take and record the patient's pulse and respiratory rates and blood pressure every 15 minutes. From 3:00 pm one day to 8:00 am the next day the operating team and I were by the side of the patient. Finally at 8:00 am respirations ceased and the blood pressure could not be obtained. Within 6 minutes and 30 seconds Dr. Churchill opened the chest, incised the pulmonary artery, extracted a large pulmonary embolus, and closed the incised wound in the pulmonary artery with a lateral clamp.

The steps Churchill took were customary at the time and understandably so. Pulmonary embolectomy then was a last minute desperate undertaking. Not many operations had been undertaken during the 23 years since Friedrich Trendelenburg (2) had attempted, without success, the first procedure in Leipzig, and most efforts had ended fatally. The first success had been achieved only 6 years before by Martin Kirschner (3) in Konigsberg, and not a single operation had succeeded in the United States. Indeed, another 34 years would go by before Richard Warren and his colleagues across town at the Peter Bent Brigham Hospital would record such a result (4).

THE IDEA

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The event of October 3rd marked a turning point in the history of surgery, not because of the way in which the patient was managedit followed the standard practicenor because of the fatal result from the pulmonary embolismit was the usual outcomebut because it gave birth to an idea, one that would eventuate in the development of the heartlung machine and would make contemporary cardiopulmonary bypass (CPB) and open heart surgery possible. In several publications (58), Gibbon told about the occasion and the idea it generated. This is how he put it in a 1970 address:

During that long night, helplessly watching the patient struggle for life as her blood became darker and her veins more distended, the idea naturally occurred to me that if it were possible to remove continuously some of the blue blood from the patient's swollen veins, put oxygen into that blood and allow carbon dioxide to escape from it, and then to inject continuously the now-red blood back into the patient's arteries, we might have saved her life. We would have bypassed the obstructing embolus and performed part of the work of the patient's heart and lungs outside the body.

Within a short periodGibbon could never recall just when this happened but it was in a matter of a day or sohis original objective was enlarged substantially. Instead of building an apparatus that could take over some of the cardiorespiratory functions and make pulmonary embolectomy a safer procedure, he would attempt to build one that could perform the entire function of the heart and lungs for a period of time, a heartlung machine that would make possible operations on the heart itself and even inside its chambers, a heartlung machine that would make CPB a reality. He did not realize at the time that 23 years would pass before he could bring this idea to fruition. CPB was on the way, but a long bumpy road stretched ahead; an intriguing pathway nevertheless, for there were persons on the roadway who did not know just where they were going and one man who did, who traversed it, and reached his goal.

Even though Gibbon spoke of the idea in his customary modest manner as one that occurred to him "naturally," the idea was unique, and it becomes even more novel when viewed from the time it was conceived (9,10). The novelty of Gibbon's plan lay in its magnitude, building an apparatus with the oxygenating capacity necessary for use in humans, one which would permit safe total CPB in humans. Gibbon later estimated that if this objective were achieved using the rotating drum techniquea very good method for oxygenating bloodthe drum would have to be as tall as a building two stories high, an estimate he still later revised to a building seven stories high!

HISTORICAL BACKGROUND

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The concept of the perfusion of blood was itself not new nor was that of a mechanical device for oxygenating blood. As long ago as 1812, Cesar-Julian-Jean LeGallois (11) made the suggestion that a part of the body might be preserved by some sort of external perfusion device, a suggestion based on the observations of other investigators that some tissues and organs of apparently dead animals could be brought back temporarily to an apparent living state by restoring the flow of blood to them. Although some studies involving the perfusion of muscles and organs were carried out in the years that followed, it was not until the middle of the century that Charles Eduard Brown-Sequard (12) pointed out that the success of such perfusions depended on the use of oxygenated blood. An interesting observation he made was the temporary disappearance of the rigor mortis of muscles of guillotined criminals when they were perfused with their own blood. From Brown-Sequard's time it was evident that supplying an adequate amount of oxygen to the blood is essential for successful perfusion and supplying the necessary amount of oxygen proved the most difficult problem in designing a mechanical CPB device.

Brown-Sequard's technique was very simple: He used syringes for perfusion and put oxygen into the dark venous blood by beating the blood vigorously, a maneuver that also defibrinated the blood. Other early investigators also used relatively simple methods for oxygenating the blood. One was that of "bubbling" the blood, a technique introduced in 1882 by Waldemar von Schroder (13) of Strasbourg. The bubbling method was based on the supposition that bubbles of a gas, such as air or oxygen passing through blood, would become surrounded by a thin layer of the blood that in turn would absorb oxygen, give off carbon dioxide, and then burst and leave the blood free of gas. The experiments that von Schroder, and subsequently others, carried out demonstrated that this method was unsatisfactory, however, because of foaming of the blood and gas embolism, difficulties that could not be overcome until antifoaming agents became available (14). A variant of the bubbling method, the "spraying" technique used by von Euler and Heymans (15) much later in 1932, only 2 years after the pulmonary embolism event in Boston, proved even more unsatisfactory, causing far too much damage to the blood to be useful. Solving the problems associated with the construction of a workable mechanism for CPB would prove to be far from simple.

It is interesting that the best technique for oxygenating the blood, the filming method, the one that would form the basis of techniques currently in use, had been proposed about 50 years previously in 1885 by Max von Frey and Max Gruber (16) of Leipzig. This method was founded on the hypothesis that a sufficiently thin film of blood exposed to oxygen would provide a good mechanism for gas exchange. Von Frey and Gruber achieved this objective by dispersing the blood as a thin film inside a rotating slanted cylinder filled with oxygen. The oxygenating capacity of their exceedingly complex apparatus was quite small, sufficient only for perfusion of isolated organs. Other investigators also used the filming method in small oxygenators of various designs. That of Richards and Drinker (17), for example, filmed the blood by having it flow down a cloth cylinder inside an oxygen chamber and that of Bayliss et al. (18) by dispersing the blood over the surface of a series of cones. Instead of cones, Daly and Thorpe's device (19) dispersed and filmed the blood on a glass cylinder down which it descended (Fig. 2.1). Thus, the basis for CPB had now been laid in the first decades of the 20th century but not for a method that would be applicable in building an apparatus for human use.



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FIG 2.1. Film oxygenator of Daly and Thorpe. This device was used for isolated dog heart preparations. Defibrinated blood was dispersed from jets onto spinning discs (F, G, H) where it filmed down three concentric glass cylinders (A, B, C). An arrangement of oxygen jets at the base provided an oxygen-rich atmosphere for gas exchange. Oxygenated blood drained through two blood outlets (M) to a reservoir through a filter and then into the left or right atria of the isolated heart where measurements of cardiac work and oxygen consumption were made. The surface area of the oxygenator was 1.1 m2, and the system was capable of flowing 600 mL/min and handling blood volumes up to 2.5 L. The entire apparatus was immersed in a larger jar filled with water at 38°C to maintain the temperature of the circulating blood and isolated heart. Hearts continued to function for up to 6.5 hours using this device. (Reprinted from Daly IB, Thorpe WV. An isolated mammalian heart preparation capable of performing work for long periods. J Physiol 1933;79:202, with permission.)

Some investigators, among them Patterson and Starling (20) and still later Hemingway (21), avoided the problem of oxygenating the blood with a mechanical device altogether by accomplishing this objective through the use of the animal's own lungs. Still others used the repetitively inflated lungs of a second "donor" animal. This was the method Jacobj (22) used in his perfusion studies of isolated organs carried out during the last decade of the 19th century. His apparatus was cleverly designed but exceedingly complicated (Fig. 2.2). Later, in their experiments with kidney perfusion, Binet and Mayer (23) helped with one of the inherent problems by describing a good method for collecting the blood from the lungs of the donor animal.



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FIG 2.2. Organ perfusion apparatus of Jacobj. This complex device relied on ventilated (R) donor lungs (chamber E 2 , right) to provide for gas exchange. At the top center, a rotating cam (M) and hinged plates (A) arrangement alternately compressed bulbs (a 1 and a 2 ) to pump blood to the organ to be perfused (chamber E 1 , left). Note presence of open flames beneath each chamber for temperature regulation and two additional chambers (B 1 , B 2 ) containing coiled tubing and thermometers to monitor blood temperature. (Reprinted from Jacobj C. Ein Beitrag zur Technik der kunstliechen Durchblutung ueberlebender Organe. Arch Exp Pathol Pharmacol 1895;36:332, with permission.)

The Russians Brukhonenko and Tchetchuline (24) also used the donor-lung oxygenator principle in their interesting studies that went a mammoth step beyond organ perfusion. Their experiments, described in 1929 (25), attempted to preserve temporary function of the guillotined heads of dogs (Fig. 2.3). The blood was oxygenated by passage through the repeatedly inflated lungs of a second dog before it was introduced by diaphragm-like pumps via the carotid arteries into the head of the subject animal. After achieving success in keeping the head functional for a few hours, Brukhonenko then used the same method of oxygenation in an attempt to bypass the nonfunctioning hearts of dogs. Some of these animals lived a short while after termination of the experiments but rarely was a temporary heartbeat restored. Unsuccessful as he was with these studies, Brukhonenko was optimistic about the potential of the method:

Our conclusions, it should be understood, are of a preliminary nature. Before finishing, let us mention, in addition an idea about the methods of artificial circulation of the blood. If the method were perfected could it not be useful in the domain of medicine and especially in the case where it is essential to replace, even if it be temporary, the insufficient work of the human heart? Without going more deeply into this question, we would express the supposition based on experience with the present work that in principle the method of artificial circulation may be applicable in man (in certain cases and perhaps even for performing certain operations upon the temporarily arrested heart) but only if an adequate technique be worked out. . .

The solution of the problem of artificial circulation of the whole body opens the pathway to the question of operations upon the heart (for example upon valves).



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FIG 2.3. Guillotined head of a dog in perfusion experiments of Brukhonenko and Tchetchuline. This preparation relied on gas exchange from a second donor dog's lungs. Diaphragm-like pumps pumped blood into the recipient dog's carotid arteries. Dog heads perfused in this manner remained functional for a few hours. (Reprinted from Brukhonenko S, Tchetchuline S. Experiences avec la tete isolee du chien.1.Technique et conditions des experiences. J Physiol Pathol Gen 1929;27:42, with permission)

Brukhonenko's vision was truly remarkable because it seems clear that he conceived the ultimate value of CPB and its potential use in humans. It is quite evident, however, that the method for oxygenating the blood he used in his experiments would not be acceptable for clinical application. Using the lung of a human "donor" would never be judged entirely safe and practical. It brings to mind the later short-lived cross-circulation method of C. Walton Lillehei et al. (26) (see Chap. 1).

Another person, far better known in the Western world than Brukhonenko, though in an entirely different field, also had a somewhat similar but less comprehensive vision, the building of a heart pump. Charles A. Lindbergh's Autobiography of Values (27) relates how the idea came to him. The miracle of flying in a mechanical apparatus made him conscious of the achievements of science in general and instigated a desire to become involved in animal experimentation. He had just married Anne Morrow, and they were in the process of making plans for their home. He decided that a biologic laboratory should be put in the basement. Lindbergh was wondering what project he should undertake, what he might do "that was not already being done," when just at this time something occurred that directed his thoughts toward building a heart pump:

My experimental interests were channeled, as so often happens, by a chance development of lifeby the illness of my wife's older sister, Elisabeth. She had contracted rheumatic fever as a secondary complication of pneumonia. A lesion had developed in her heart, restricting her activities until her doctor recommended a year of complete rest in bed. Since a remedial operation of the heart was impossible, he said, her life would be limited both in activity and length. I asked him why surgery would not be effective. He said the heart could not be stopped long enough for an operation to be performed because blood had to be kept circulating through the body. I asked why a mechanical heart could not maintain the blood circulation temporarily while the heart was being operated on. He replied that he did not know. He had never heard of a mechanical heart being used.

The same answer came from other doctors. While Lindbergh was waiting with the obstetrician and the anesthetist the night his wife was in labor with their first child, he asked the question once more. Although neither could give an answer, the anesthetist ventured the opinion that a man he knew likely could provide one. This conversation led to a meeting with Alexis Carrel, winner of the Nobel Prize and at the time director of the Rockefeller Institute for Medical Research. Lindbergh's idea was discussed thoroughly and Carrel brought up problems associated with the pumping of blood, such as clotting, infection, and hemolysis. Carrel pointed out, for example, that during a period of 20 years he had never been successful in building an infection-free organ perfusion apparatus. The result of the meeting was Lindbergh's appointment to work in Carrel's institution.

Some have assumed that Lindbergh envisioned a heartlung machine and CPB, but a thorough search of all relevant material negates the idea that this was his dream. Instead, his dream was of a heart pump and not an extracorporeal circuit incorporating a machine for oxygenating the blood. In this regard, Richard Bing (28), who was working at the Institute then, wrote about the research on which Lindbergh embarked:

Charles Lindbergh's ideas immediately caught Carrel's imagination. He had always considered the concept of organ culture to be a logical extension of the concept of cell culture; but he was also aware of the considerable difficulties in designing a system for cardiorespiratory bypass, primarily because of the need to instill oxygen into the perfusate. . . . In my work with both Lindbergh and Carrel in the early 1930s, I never heard either of them refer to Lindbergh's original idea as a system for cardiopulmonary bypass. . . . Carrel convinced Lindbergh that, instead of venturing into a difficult and unexplored field, it would be wiser to attempt the culture of whole organs, which could become an immediate reality.. . .

The great advantage of Lindbergh's contribution was that it permitted sterile, pulsatile perfusion at variable "pulse rates" and variable perfusion pressures. . ..

Thus the perfusion system [of Lindbergh] developed into a tool that helped fulfill Carrel's wish to study the interplay between organ, blood, and lymph. An intellectual disciple of Claude Bernard's, Carrel was interested in study of the internal environment through study of the interplay between tissue fluid and organ.

In 1935, Lindbergh (29) gave details of this work with his perfusion device (Fig. 2.4), and a book on organ culture was published by Carrel and Lindbergh in 1938 (30).



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FIG 2.4. Perfusion system of Lindbergh and Carrel. This elaborate blown-glass device provided sterile pulsatile perfusion of various organs using regulated compressed air to vary the pressure and perfusion rate. The organ chamber is the slanted portion (4) at the top. Cotton-filled bulb chambers (1, 2, 12, 22) prevented bacterial contamination of the organ and circulating fluid. Floating glass valves and other chambers provided regulation of internal and external pressures on the organ. Perfusate was filtered through a column of silica sand (6). Temperature of the organ and circulating fluid was maintained by placing the entire apparatus in an incubator. (Reprinted from Lindbergh CA. An apparatus for the culture of whole organs. J Exp Med 1935;62:415, with permission.)

Lindbergh then clearly appreciated the potential value of a heart pump but neglected the important issue of oxygenating the blood. Brukhonenko went further, recognizing this need but providing no practical mechanism for accomplishing the task. Neither had in mind an essential componenta practical mechanical oxygenator suitable for human use. Incorporating such a mechanism into the perfusion system was indeed the primary stumbling block, and no one had tackled the problem or even conceived a suitable plan. Very shortly, however, Jack Gibbon walked onto the stage.

JOHN H. GIBBON, JR.

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John H. Gibbon, Jr.1 (31) was born in Philadelphia in 1903, the son of a professor of surgery and co-chairman of the surgical department at the Jefferson Medical College. Jack's early years at home in Philadelphia, on the farm in Media, and at the Penn Charter School and his young adult life at Princeton gave no indication that he would become a surgeon. Once the usual boyhood devotion to acts of physical prowess subsided, his ambition changed; he wanted to become a poet and writer. Persuaded by his father that a medical degree would do no harm and would not make him write less well, however, he entered the Jefferson Medical College.

Studying medicine was not by any means unusual in the Gibbon family. Indeed, his great-great-great-grandfather, James Lardner, was a physician in London, and five generations of Gibbons before Jack were doctors. Furthermore, there were doctors in the family of his grandmother Gibbon, two born in the colonies in 1699 and in 1731, respectively, and later three cousins. Also, the Jefferson Medical College was a logical choice for his studies. Jack's grandfather Gibbon, named Robert like his father and grandfather, studied medicine. He was the first to obtain his medical education at the Jefferson Medical College where both his son and grandson would hold surgical professorships. Not only his paternal grandfather but his uncle, his father, and his cousins as well were all graduates of Jefferson. So the would-be poet entered medical school, graduated, and became the sixth Gibbon in a direct line of descent to become a doctor.

Jack's ancestry was remarkable not only for the predilection for a medical career. Toward the close of a distinguished 43-year service in the army, his maternal grandfather, General Samuel S. B. Young, became its first chief of staff. His great uncle John Gibbon, a West Point graduate and career soldier, culminated his military service by stopping Pickett's charge at Gettysburg, during which he was wounded in close combat. Jack's great-grandfather Robert Gibbon, a doctor, became assayer of the United States mint at Charlotte, North Carolina. One of their sons, Lieutenant Lardner Gibbon, explored the Amazon with Lieutenant W. L. Herndon as a United States naval officer and wrote and illustrated the second of the two excellent published volumes that described their discoveries. Members of Jack's family, like those of other families, fought on both sides during the Civil War. With its onset, Lardner Gibbon, who had left the United States navy some years before, joined the Confederate forces and rendered excellent service as a surgeon and quartermaster in the same regiment of the Army of Northern Virginia in which his brother, Captain Nicholas Gibbon, served. Nicholas had intended to follow his father and brother into medicine, but the war interrupted these plans. After it was over, he settled down in North Carolina as a farmer and was active in local and state politics, holding office as a justice of the peace and as a member of the state General Assembly.

Robert Gibbon's wife, Mary Amelia Roberts, Jack's maternal grandmother, came from a family distinguished in the ministry. Her father, Zabdiel Rogers, was a Congregational minister and spiritual leader of a church in Charleston, South Carolina but was not the first churchman in the family. John Rogers was a minister in Suffolk County, England. His second son, Reverend Nathaniel Rogers, emigrated to America in 1636.

Jack's parents then might well have anticipated that their first son would lead a useful life and likely a distinguished one, but they had no reason whatsoever to foresee that he would become a surgeon or that he would make one of the great surgical contributions of all time, that he would carry out investigations that would render human CPB feasible and in this way revolutionize surgery.

PURSUIT OF THE IDEA

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When Jack returned to Philadelphia from a year in Boston working as a fellow in Churchill's laboratory, he not only brought along his haunting idea of a CPB machine but also his technical assistant and newly married wife, Maly Hopkinson, who for years would continue to work closely with him as a real partner in his investigative efforts. The time in Philadelphia provided no opportunity for starting the search for a human CPB device. Jack practiced surgery in the mornings and in the afternoons worked in the Harrison Experimental Surgical Laboratories at the University of Pennsylvania where he had obtained a staff appointment. Although he could not tackle the project, which was always on his mind, he had a profitable, indeed stimulating, time working in association with Eugene Landis, later professor of physiology at Harvard. When Jack discussed his idea of a heartlung machine and CPB with his colleagues, he met with little or no encouragement, all too often the way new concepts are received. In general, they thought he would be wiser to investigate smaller projects, ones more certain of a successful conclusion, ones that would more likely give him an opportunity to publish his observations and thus advance his chances in the academic world. The principle of publish or perish was alive and well. Only Eugene Landis encouraged him to proceed. Jack was not dissuaded by the majority opinion, and when he was offered another fellowship year in Boston he gladly accepted it. Now he could begin to build the forerunner of his ultimate objective.

Those who work today with the relatively easily managed, small, efficient oxygenators and extracorporeal bypass circuits can hardly appreciate their humble beginnings. Fortunately, both Jack and Maly have described them. In Jack's address, published in 1978 (1) after his death, the early efforts were related:

We . . . decided upon a vertical revolving cylinder in which the blood was introduced tangentially at the top of the cylinder in the direction of the rotation. Rotation of the cylinder kept the blood in a thin even film by centrifugal force avoiding rivulets. . . . The cylinder was tapered at the bottom to a knife-like edge, where the blood was collected in a stationary cup whose inner surface closely approximated the outer edge of the cylinder. From the cup at the bottom of the oxygenator the now red blood was returned to the animal's body through a systemic artery in a central direction.

Imagine for a moment the way research was carried out in a research laboratory in the 1930s. The Federal Government was not then pouring out millions of dollars to doctors to perform research. Harvard provided my fellowship and the Massachusetts General Hospital provided the laboratory. I bought an air pump in a second hand shop in East Boston for a few dollars, and used it to activate finger cot blood pumps. Valves were made from solid rubber corks with the small end cut transversely three quarters through to form a flap about 2 mm thick. With this flap held up, a cork borer was longitudinally passed through the center of the rubber stopper, thus creating a channel for the stream of blood. These simple valves worked well. Plastic materials were not available, so our circuit was largely rubber and glass. Heparin had just become available, but its antagonist, protamine, was not.

He gave a vivid account of the device on another occasion (7) (Fig. 2.5):

This assemblage of metal, glass, electric motors, water baths, electrical switches, electromagnets, etc. looked for all the world like some ridiculous Rube Goldberg apparatus. Although the apparatus required infinite attention to detail it served us well and we were very proud of it. The heartlung machines in use today bear as little resemblance to that early model as the jet plane of today bears to that magnificent conglomeration of wires, struts, and canvas that sailed into the air in 1905 from the dunes of Kitty Hawk with one of the Wright brothers at the controls.



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FIG 2.5. Early extracorporeal circuit of Gibbon. Venous blood was withdrawn by a finger-cot pump (E, F) and transmitted to the inner wall of a vertical rotating cylinder (A, left) where it was exposed to an atmosphere of 95% oxygen and 5% carbon dioxide for gas exchange. A water manometer (T) measured air pressure in chamber S and gave an indication of total blood flow. Blood was collected in a lower chamber (B) and then forced back into the animal's artery by another finger-cot pump (E', F'). Using this apparatus, Gibbon and his wife, Maly H. Gibbon, were able to support the cardiorespiratory needs of cats for up to 68 minutes during occlusion of the pulmonary artery. (Reprinted from Gibbon JH Jr.Artificial maintenance of circulation during experimental occlusion of pulmonary artery. Arch Surg 1937;34:1108, with permission.)

Sometimes Jack and Maly saved money by walking about the Boston streets at night securing cats without expense. As Jack put it (5), "I can recall prowling around Beacon Hill at night with some tuna fish as bait and a gunny sack to catch any of those stray cats which swarmed over Boston in those days. To indicate the number the S.P.C.A. was killing 30,000 a year."

When the year 1934 ended in Boston and the Gibbons returned to Philadelphia, it was possible to continue work on the CPB apparatus, and in a year the machine had been improved to the point that it was satisfactory for the studies being undertaken at the time. The blood vessel cannulas were silver coated and thin walled. A piston-type air pump was being used. The oxygenated blood was delivered into the femoral artery in continuous flow with pulsatile increments. Ether was administered directly to the cats until the extracorporeal circulation took over most of the work of the heart and lungs and then was added as needed to the oxygenating device. Fortunately, no accident occurred with this potentially explosive mixture of ether and oxygen. Improved as the apparatus was, it was primitive in retrospect. So were the experiments that Maly recalled in this way (personal communication, Marly H. Gibbon, reminiscences, 1963):

To do these experiments we had to be at the laboratory bright and early, as they often continued all that day and sometimes well into the evening. We could only manage three such experiments a week. First we had to smoke a kymograph record and get it in place on the operating table. Then, we had to bring a cat down to the laboratory from its upstairs quarters and anesthetize it . . . perform a tracheotomy and connect the animal to an artificial respirator while a "Drinker Preparation" was being done, in order to expose the pulmonary artery in a (later) naturally breathing animal. . . . These preparations usually took four or five hours and it was midday before we were ready to start the really critical part of the experiment: gradually closing the clamp around the pulmonary artery and at the same time withdrawing blood from the jugular vein [into the apparatus]. . . .

We would keep the clamp completely occluding the pulmonary artery for as long as we thought the cat could stand it, or nothing went wrong with the apparatus, but the things that were apt to go wrong were infinite. . . . [After] the period of occlusion of the pulmonary artery, [we would] remove the clamp around it, and then put the cat back on its own circulation and see if it could maintain its blood pressure at a near normal level and its respirations at a near normal rate. If it succeeded in doing this, the animal was nursed tenderly over a period of an hour or so . . . the kymograph record was shellacked so no diener's hand or broom should smooch our record, the instruments and general mess cleaned up, and we could go homea long day.

A long day it was, but the Gibbons had brought CPB over a high hurdle. In 1967, Jack (6) recalled the event:

I will never forget the day when we were able to screw down the clamp all the way, completely occluding the pulmonary artery, with the extracorporeal blood circuit in operation and with no change in the animal's blood pressure! My wife and I threw our arms around each other and danced around the laboratory.

Animals were surviving a period of total CPB, and total CPB in humans was nearing reality. Jack's address was concluded with these remarks:

Although it gives me great satisfaction to know that open-heart operations are being performed daily now all over the world, nothing in my life has duplicated the joy of that dance around the laboratory of the old Bullfinch Building in the Massachusetts General Hospital 32 years ago.

When the Gibbons returned to Philadelphia it was possible to continue work with the CPB circuit and to improve it (Fig. 2.6). After Jack reported to the 1939 meeting of the American Association for Thoracic Surgery that indefinite survival of cats in good condition had been achieved after a period of total CPB, Clarence Crafoord, widely respected head of thoracic surgery at the Karolinska Institute in Stockholm, said that a virtual pinnacle of success in surgery had been reached. Leo Eleosser, a distinguished San Francisco surgeon, remarked that Jack's work reminded him of the visions of Jules Verne, thought impossible at the time but accomplished somewhat later. These comments were unpublished but later recounted by Dr. Gibbon (8,32). CPB had surely come a long way, but its applicability in a human operation was still some years off.



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FIG 2.6. Modified extracorporeal circuit of Gibbon. This apparatus was used in later experiments when the pulmonary arteries of cats were occluded for prolonged periods with survival (one gave birth to a litter of kittens after the experiment). Note that the apparatus is similar in design to the one described in 1937 (see Fig. 2.5), but DeBakey roller pumps are now used to withdraw and return blood to the animal's circulation, thus eliminating the need for valves. A photoelectric blood level sensor is shown (L) near the collection chamber (lower left) and was used to servoregulate the arterial pump (F') and avoid air embolism. Similarly, a pressure sensor on the venous line (H) was used to servoregulate the venous roller pump to control the degree of suction applied to the animal's venous system. The average pump flow was approximately 250 mL/min (100 mL/kg body weight) and the maximum total flow possible was 500 mL/min. (Reprinted from Gibbon JH Jr.The maintenance of life during experimental occlusion of the pulmonary artery followed by survival. Surg Gynecol Obstet 1939;69:604, with permission.)

INTERRUPTION AND THEN RENEWED LABORATORY WORK

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The onset of World War II prompted Jack to volunteer for military service, and this necessitated deferring further work on his project just as it had reached its most promising stage. When he took off his army uniform 4 years afterward in 1945, however, a piece of truly good luck came his way, as if in a way a reward for his patriotic service. Through a first-year Jefferson medical student who knew of his work and whose fiancee's father was a friend of Mr. Thomas Watson, chairman of the board of directors of IBM, a meeting with this far-sighted business executive was arranged. Mr. Watson had familiarized himself with Jack's work by reading reprints of his publications (3336) and asked how he might help. Jack explained that he needed engineering assistance and added bluntly that he did not want to make any money from his idea nor did he wish IBM to do so. Watson agreed and assured Jack of the help he needed. Soon talented engineers from the corporation were working with him. No longer was this a nickel and dime operation.

A larger machine using the same rotating drum principle was soon made, each part carefully tested and constructed of the finest materials. Now the experiments yielded better results. Half the animals survived indefinitely after a period of total CPB of more than 0.5 hours. The realization that the much greater flow necessary for human use would require a drum of enormous size made it evident that the oxygenator had to undergo a drastic change. The observations of T. Lane Stokes and John Flick, Jr. (37), two young doctors working with Jack at the time, put the project on a promising pathsome turbulence of flow could increase oxygenation as much as eight times. Using a screen for the oxygenator could produce the desired turbulence. One was built and worked well (Fig. 2.7). Now all the dogs survived bypass periods of up to 4 hours in good condition. A device suitable for human use was then constructed, a machine with multiple stationary vertical screen oxygenators through which the blood flowed down in an atmosphere of oxygen and carbon dioxide. Tests on large dogs went well. Indefinite survival followed prolonged exposure of the atrial septum, incision of the ventricle and bringing its septum into view, and repair of created septal defects (38). It seemed at long last that everything had been done to make certain CPB in humans was feasible, and at the May 1952 meeting of the American Association for Thoracic Surgery, Jack (39) could say "I believe that we are approaching the time when extracorporeal blood circuits of the mechanical heart lung type can be safely used in the treatment of human patients."



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FIG 2.7. Stationary screen extracorporeal circuit used by Gibbon in animal experiments just before clinical applications. Two roller pumps (D and P) are used to withdraw and reinfuse blood from the animal. A third roller pump (E) recirculates oxygenated blood by withdrawing it from the tubing line to the arterial pump (P). This maintained a constant supply of blood that was filmed down a series of screens (J) contained in an oxygen-rich atmosphere for gas exchange. A screen filter with stopcock (Q) is located in the arterial tubing line for blood filtration just before its reinfusion into the animal's artery. (Reprinted from Miller BJ, Gibbon JH Jr, Gibbon MH. Recent advances in the development of a mechanical heart and lung apparatus. Ann Surg 1951;134:699, with permission.)

CLINICAL APPLICATIONS: GIBBON AND OTHERS

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As not infrequently happens, the first attempts were failures: a March 1951 exploration of the right atrium under partial bypass in a terminally ill patient under the erroneous diagnosis of a myxoma or large clot and a February 1952 exploration of the atrium under total CPB in a moribund infant also under the erroneous diagnosis of a septal defect. Cardiac catheterization was not a common diagnostic aid in those early days, and errors were sometimes made from ordinary clinical assessment.

Once Jack's experimental work was well under way, others attempted to design, build, and test devices for CPB. Jack welcomed these efforts, and all who were interested were free to visit his laboratory and share his experiences. Priority was not his goal. By May 1952 when Jack told those at the meeting of the American Association for Thoracic Surgery that he thought the time had come when CPB could be used in humans, it had indeed been used in three instances, although only once for an open heart procedure. In August 1951, Mario Dogliotti (40) in Turin had used his bubble oxygenator as a precautionary measure in removing a large mediastinal tumor. In the same year James Helmsworth et al. (41) in Cincinnati reported having used his in an effort to relieve severe heart failure, and in April Clarence Dennis et al. (42) used the rotating screen oxygenator he had developed at Minnesota in a fatal attempt to treat a patient thought to have an atrial septal defect but who had instead an atrioventricular canal. Not long after this effort, Dennis had another unsuccessful experience, this time due to a mistake made by the person operating the pumpoxygenator (43).

CPB had not been used successfully for an open heart procedure when 18-year-old Cecelia Bavolek became Jack's patient. Despite cardiac catheterization and angiography, the physicians at the Jefferson Hospital found the diagnosis troublesome. They concluded, however, that an atrial septal defect with a large left-to-right shunt was the correct diagnosis, and Jack agreed. Arrangements for the operation were made.

It was May 6, 1953 when Cecelia was brought to the operating room. Her heart was exposed through a bilateral fourth intercostal incision. Digital exploration of the atrium revealed a defect the size of a silver dollar. The left subclavian artery was cannulated as were the inferior vena cava through the atrial appendage and the superior cava through the atrial wall. Partial bypass was begun, a vent was placed in the left ventricle, and total bypass instituted. The defect was exposed and closed with a continuous suture reinforced with a single suture at each end. The atrial incision was closed. The extracorporeal circuit had been in place 45 minutes. The patient had been on total CPB for 26 minutes. She made an uneventful recovery. The feasibility and usefulness of CPB in humans had at long last been demonstrated. Jack had achieved success in a human (44), and his two decades of innovative and difficult work had been justified. His goal had been reached, and he was ready to leave to others the advances he knew would be made.

CPB had arrived and was here to stay.

GIBBON'S CONTRIBUTIONS TO CARDIOPULMONARY BYPASS IN CLINICAL PRACTICE

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It is remarkable that John Gibbon recognized long ago so many of the essential elements of a safe and efficient apparatus for CPB and the desirable features of its secure and trustworthy use. It is doubtful that he foresaw clearly the highly trained expert professional perfusionists of today. It was consequently his desire to incorporate in the device itself every possible safeguard. He knew that major mistakes in its operation could lead to undesirable and even potentially fatal consequences. He wanted the CPB apparatus and its use to be as foolproof as possible. From 40 to 60 years ago, Gibbon used or suggested many practices currently in use with CPB. Ideally, he knew, the surface contact with blood should be inert, friendly, one might say, to the blood passing along, and this passage of blood should provide the patient with adequate circulation of undamaged properly oxygenated blood and a means for its release of carbon dioxide.

When the perfusionist Mark Kurusz looked over Gibbon's published work in 1982 (45), he listed these important contributions: the rinsing of the circuit before CPB, the use of colloids for the priming solution, and a small rather than large priming volume to reduce hemodilution. They also included the importance of measuring the oxygen saturation of the venous blood for assessing tissue perfusion and the arterial Pco 2 that he believed should be kept at a normal or slightly depressed level. Gibbon thought the systemic blood pressure should be maintained at a level of at least 50 to 65 mm Hg and that the perfusate and the blood trapped in the apparatus at the completion of CPB and the fluid collected by chest tube drainage should be salvaged and returned to the patient. He considered the heparin/protamine titration test after CPB once it became available.

His equipment included safety devices, both audible and visible, for shutting off the pump automatically in case the blood in the reservoir reached too low a level or the line pressure became too high. The inhalational anesthetic was switched to the oxygenator once CPB was established. He experimented with pulsatile flow, incorporated an in-line pH meter and a device for arterial filtration, used thin-walled stainless steel cannulas and, once it became commercially available, plastic tubing.

Dr. Gibbon demonstrated that successful operative procedures in heparinized subjects and secondary operations were possible if proper hemostatic techniques were observed. He knew that the amount of hemolysis was related to the length of CPB but that the degree of hemolysis was compatible with good outcome. He recognized that postoperative bleeding was likely to be troublesome after long periods of CPB but could be managed by administration of fresh blood and the passage of time. He knew of the danger of leaks on the negative side of the pump, described the phenomenon of heparin rebound, noted that protamine could produce hypotension, observed the differential cooling of the myocardium with hypothermic cardioplegia, and advocated the use of myocardial temperature probes.

Importantly, for the overall safety of the subject, he was aware of the immense value of an assistant who could give undivided attention to the CPB, the forerunner of the thoroughly competent perfusionist of today.

KEY POINTS

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The impetus for Dr. John H. Gibbon, Jr. to develop a heartlung machine was the witnessing of a patient's death from pulmonary embolism and failed pulmonary embolectomy (Trendelenburg operation) in 1930.

The concept of organ and tissue perfusion with oxygenated blood was demonstrated several times in the 1800s, beginning with the work of LeGallois in 1813.

Early perfusion devices had limited capability to exchange gases, which limited their use to isolated organ experiments.

Physiologists used methods such as whipping, bubbling, spraying, and filming venous blood to add oxygen and remove carbon dioxide in laboratory experiments.

Alternative blood "oxygenators" were the native lungs of donor animals, which were also successful in preserving temporary function of perfused organs.

In 1929, Brukhonenko speculated that artificial circulation of blood might someday be applicable for cardiac operations in humans.

In 1935, Lindbergh and Carrel described a sophisticated pumping apparatus for organ perfusion experiments.

Dr. Gibbon received little encouragement when he set out to develop a workable heartlung machine in the mid-1930s.

In 1939, Gibbon reported survival of cats in experiments that involved gradual occlusion of the pulmonary artery while gas exchange and perfusion were taken over by a rotating cylinder film oxygenator.

In the late 1940s and early 1950s, Gibbon received engineering help from the IBM Corporation to develop a larger capacity oxygenator consisting of stationary screens, which induced mild turbulence in the blood, for potential application in humans.

After many successful experiments in dogs in which septal defects were created and repaired, a heartlung machine was built and used clinically by Gibbon in February 1952, but an erroneous preoperative diagnosis contributed to the death of the infant.

Other workers who clinically used extracorporeal circulation in the early 1950s were Dogliotti, Helmsworth, Dennis, and Lillehei.

On May 6, 1953, the Gibbon-IBM heartlung machine was used successfully by Dr. Gibbon during closure of an atrial septal defect in an 18-year-old girl.

Careful review of the publications of John H. Gibbon, Jr. revealed he was a meticulous investigator who solved many problems inherent with CPB and described practices still used today.

References

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