Heart: An American Medical Odyssey (40 page)

Relying on the ready availability of an identical twin would obviously not succeed as a durable organ procurement strategy. What was needed was a way to overcome the natural process of tissue rejection. During the 1950s, multiple drugs to attenuate the immune response (immunosuppression) were evaluated, including nitrogen mustard (originally evaluated as a chemical warfare agent) and 6-mercaptopurine (a drug used for cancer chemotherapy). Because of their toxicity, both were deemed unsuitable.

Following the observation that many of the survivors of the atomic bombings of the Japanese cities of Hiroshima and Nagasaki had damaged immune systems,
total
body irradiation was used in the 1950s. The strategy contributed to the first successful kidney transplant between nonidentical twins, but it was risky and occasionally resulted in the death of the patient.

Shumway and Lower, writing in a 1961 paper, were optimistic that a solution to rejection would be found:

The precise mechanism by which the host causes the death of the homologous cells is not known. One must assume that, as these mechanisms are clarified, an appropriate means will be found of altering either the elaboration of the homologous antigen or the immunologic response of the host without injury to either graft or host.

The solution soon turned out to be a combination of the drugs azathioprine (a less toxic derivative of 6-mercaptopurine) and prednisone (a steroid). The pair became part of the standard antirejection cocktail for the next twenty years.

•  •  •

At the end of 1963, Dr. James Hardy’s team at the University of Mississippi prepared to perform what they hoped would be the world’s first heart transplant. Hardy had already made news earlier in the year when he performed the world’s first lung transplant. The patient, fifty-eight-year-old John Richard Russell, an inmate sentenced to death for a 1957 killing in Attala County, Mississippi, had been diagnosed with cancer of his left lung. Hardy proposed to remove the diseased lung and transplant a new, cancer-free organ.
On June 11, 1963, Russell became the first patient to undergo a lung transplant.
Ten days later, the Associated Press reported that Governor Ross Barnett had pardoned Russell because his participation in the surgery would help to “alleviate human misery and suffering [for] years to come.” Russell died from renal failure about a week after his pardon.

Six months later, as Hardy and his team readied themselves for
what would be historic surgery to transplant a heart, they faced a difficult problem that every other team in the United States encountered: the very definition of death.

Unlike the current era, in which brain death (the irreversible end of all brain activity) defines the end of life, in the 1960s, the cessation of a perceptible heartbeat was the typical criterion used to declare a person dead. This created a difficult technical issue in that a heart could not be harvested from a donor until the donor heart stopped beating. This required a surgical team to stand vigil, awaiting the moment the heart stopped, and then excise the organ immediately in an attempt to retain its viability.

In a 1964 paper in the
Journal of the American Medical Association
describing his first operation, Hardy laid out the technical problem:

But how soon after “death” of the donor could the heart be removed? If it were not done promptly, irreversible damage might have occurred. To minimize such damage it was planned to insert catheters into the femoral vessels and begin total body perfusion the instant death was announced by a physician not associated with the transplant team. . . . In this way, oxygenation of the body tissues could be affected while thoracotomy was performed to excise the donor heart and begin coronary sinus perfusion.

At the outset, it was expected that months, or even years, might elapse before a suitable donor and recipient died simultaneously in the small University Hospital.

Hardy had been concerned that while there should be no difficulty identifying a suitable recipient for a new heart, it might be hard to find suitable donors. To his surprise, in late December 1963, three patients with fatal brain injuries were admitted to his hospital: one with trauma from a fall, one with a brain tumor, and another with a self-inflicted gunshot wound to the head. All three of the patients died after a period of time on a respirator. Hardy rhetorically asked:

When, if ever, would a physician be justified in switching off the ventilator in a patient whose voluntary respiratory effort had long ceased, to permit the hypoxia that would be followed by cardiac arrest? We were not able to conclude that we would be willing to do this, despite the fact that at some point fruitless resuscitation efforts must cease if a viable kidney, heart, or other organ were to be obtained for transplantation to a recipient.

Lacking today’s organized network of hospitals perpetually on the lookout for possible organ donors and the contemporary definition of brain death, Hardy made a bold decision:

Since we were not willing to stop the ventilator, we had concluded that a situation might arise in which the only heart available for transplant might be that of a lower primate.

On January 21, 1964, Boyd Rush, a sixty-eight-year-old semicomatose, deaf-and-mute male with atrial fibrillation and gangrene of the left leg, was admitted to Dr. Hardy’s hospital in critical condition. Although the patient’s leg was amputated the next day, his condition continued to deteriorate. It was felt that his gangrene, as well as his declining mental status, was likely the result of embolized blood clots from his heart (probably a consequence of atrial fibrillation). On January 23, as the patient neared death, Dr. Hardy brought him to the operating room and placed him on the heart-lung machine. At the same time, a potential heart donor lay critically ill in the hospital, but his demise was not thought to be imminent. Hardy polled his teammates and by a vote of four to one, they voted to use the heart of a chimpanzee.

In one operating room, the chimpanzee was anesthetized and his heart was removed, preserved with cold oxygenated blood, and brought into the adjacent operating room where Mr. Rush was supported by the heart-lung machine. Using the technique that Hardy had perfected in the animal laboratory, the heart of the patient was carefully excised and the chimpanzee’s sutured into its place. In Dr. Hardy’s words:

A regular and forceful beat was promptly restored following defibrillation with a single weak shock of the pulse defibrillator.

Unfortunately, the heart of the chimpanzee was too small to support the circulation of the much larger man. The patient died in the operating room. Hardy’s bold experiment had failed to save Mr. Rush’s life, but it was the first time the surgical techniques to transplant a heart had been tested in a human being, and the experience helped to set the stage for what would come next.

•  •  •

In the fall of 1965, Dr. Richard Lower moved from Stanford University to the Medical College of Virginia to assume the job of chief of cardiac surgery, where he continued his heart transplantation research. In May 1967, Lower was intent on proving that a human heart could be removed from a recently deceased donor, revived, and then used for transplant. Both Lower and Shumway had shown that this could be done with dogs, but it had yet to be proven that it could be accomplished with a human heart.

In a reverse of the procedure performed three years earlier by James Hardy, Lower took the heart from a recently deceased patient, revived it with cold saline, and, using the technique that Shumway and Lower had developed at Stanford, transplanted it into the chest of a baboon. Perfused now with warm and oxygenated blood, the human heart began to beat inside the primate, the first time a human heart had been used as a donor organ. Lower had intended his experiment as proof of the concept that a “fresh” cadaver heart could be successfully resuscitated, and he had done just that. As Donald McRae states in his excellent book
Every Second Counts: The Extraordinary Race to Transplant the First Human Heart
, “It was another measured step toward the first full-scale clinical attempt between a human donor and a human recipient.”

•  •  •

In Brooklyn, Dr.
Adrian Kantrowitz was also getting ready to perform a heart transplant. He understood the challenges posed by graft rejection and had focused his attention on cardiac transplantation in infants. Although the surgery
“was harder technically and emotionally” than surgery on adults, because infant
immune systems are immature, Kantrowitz knew infants were less likely to reject the donor organ. To prepare for his first case, Dr. Kantrowitz and his team worked in the lab for years performing hundreds of procedures on puppies, perfecting a technique to be used for the transplantation of a human heart about the size of a walnut.

Kantrowitz was a remarkable innovator. During his long and distinguished career, first at Maimonides Medical Center in Brooklyn and later at Sinai Hospital in Detroit (now called Sinai-Grace Hospital), he developed more than twenty devices, including an electronic pacemaker, multiple LVADs, and the intra-aortic balloon pump (an easy-to-use temporary heart assist device that I have used hundreds of times to treat critically ill patients).

In June 1966, Kantrowitz and his team had been poised to perform the world’s first heart transplant. A baby with anencephaly (a terrible and rapidly fatal congenital malformation marked by absence of the brain) had been born in Portland, Oregon, and in an act of heroic generosity, the parents offered their son’s heart to an infant in Brooklyn who was dying from a congenital heart defect. The anencephalic child was flown to New York and prepared for surgery that would make history. As the definition of death in 1966 required the absence of circulation, Kantrowitz was required to wait until the child’s heart stopped beating. When that sad moment finally came, the little heart could not be revived, and Kantrowitz was forced to
abandon the transplant.

•  •  •

On December 3, 1967, one month after the first test flight of the Saturn V moon rocket, the race to perform the first human heart transplant was won in Cape Town, South Africa.

The surgeon was Dr. Christiaan Barnard, a dynamic forty-five-year-old who early in his career trained in Minnesota with surgical legends Dr. Owen Wangensteen and Dr. Walton Lillehei. After his training, Dr. Barnard returned to Cape Town and joined the staff at Groote Schuur Hospital. In the mid-1960s, Dr. Barnard became interested in heart transplantation and developed an animal lab, but unlike many of his American counterparts, Barnard’s team focused mostly on honing their operative technique, relying on the long-term animal results published by some of their counterparts in America. In an interview for David K. C. Cooper’s book
Open Heart,
Barnard said,
“All we were interested in was perfecting the surgical technique.”

Louis Washkansky was a fifty-eighty-year-old man, originally from Lithuania, who had suffered three heart attacks in 1965 and was dying of congestive heart failure at Groote Schuur Hospital. In life, he had never met
Denise Darvall, a twenty-five-year-old woman who worked at a bank. On December 2, 1967, Denise’s young life ended when a car struck her and her mother, Myrtle, as they crossed a street after leaving a bakery. Myrtle died at the scene, and Denise was brought to Groote Schuur in critical condition with a crushed skull.

When Denise’s neurological injury was determined to be nonsurvivable, her father, Edward Darvall, was approached about donating her heart to Mr. Washkansky. Despite having just lost his wife and daughter, Mr. Darvall somehow mustered the strength and selflessness to donate his child’s heart.

In 1967, the law in the United States required that the heart stop beating before a patient could be declared dead and an organ harvested. In South Africa, a brain-dead patient with a still-beating heart could be declared dead by the consensus of two neurosurgeons, and theoretically the heart could be removed while it still beat, a far better option from the standpoint of graft and, likely, recipient survival.

On December 3, Louis Washkansky and Denise Darvall were taken to separate operating rooms. Barnard told David Cooper that although South African law would have permitted him to remove the
still-contracting heart, he decided to wait for the heartbeat to cease:

I decided I would not take out Denise’s heart while it was beating, not even open the chest. I was scared that I would be criticized. Although we had discussed it with the forensic medicine people, and they said it would be no problem, I decided not to do that. When we had Washkansky’s chest open and we were ready to connect him to the heart-lung machine, I went to the donor and I disconnected the respirator myself. We waited. She didn’t breathe. After about five or six minutes, her heart went into ventricular fibrillation. I then said to my colleagues to open the chest and remove the heart.

Marius Barnard, Christiaan’s brother and a crucial member of the surgical team, told Donald McRae for his book
Every Second Counts
that the process of waiting for the donor’s heart to stop beating was more complicated than that.
According to Marius, disagreement arose among some team members who were opposed to removing Denise’s heart while it was still beating. To shorten the time it would take for the heartbeat to cease after Denise was taken off the ventilator, the donor was given an injection of potassium, which stopped the heart (an at-best ethically ambiguous action), and then harvesting began.

Marius told
Life
magazine:

Now we’ve got the heart in a donor, oxygenated and being cooled. We’ve got the recipient, on the bypass machine, also being cooled and ready. Now things are going. Now the whole thing is on. Now we remove the heart of the recipient and cut out the heart of the donor.

Using the techniques pioneered by Richard Lower and Norman Shumway, Barnard sutured Denise Darvall’s twenty-five-year-old heart into Louis Washkansky’s chest. After all the suture lines were complete,
the heart was defibrillated with an electrical shock. Marius’s description in
Life
captured the moment history was made: