Beating a new path

With detours through war zones, animal surgeries and ethical questions, the road to safe heart transplants has been anything but smooth.

 Illustration by  Tegan Iversen

Illustration by Tegan Iversen

Historically, the heart was regarded as the seat of human emotion and the soul. For a long time the heart was considered to be too sacred and delicate to interfere with. Today, with an improved understanding of human anatomy the heart, like many other organs, can be replaced by transplant.

The first human heart transplant took place nearly 50 years ago. In South Africa, Dr Christiaan Barnard and his surgical team removed the heart of Denise Darvall, a young woman who had been fatally injured in a car crash. They then transplanted it into Louis Washkansky, a 55-year-old who was slowly dying of heart disease. After about four hours of surgery, a single jolt of electricity started the transplanted heart beating in its new owner’s chest.

Many steps on the road to a milestone

It is tempting to talk about revolutionary milestones such as the first heart transplant as isolated and dramatic leaps forward. Yet, this popular narrative rarely reflects the true nature of scientific and medical advances, and the first heart transplant was no exception. Centuries of research, medical improvements and discoveries had to accumulate to make the first heart transplant possible. Advances in surgical techniques, immunology, and anaesthesia all contributed to that first miraculous surgery. Some of the researchers and clinicians may not have even realised their work was leading to this incredible outcome at the time. Some of the work was done with transplantation as the end goal; some was conducted without heart transplants even being imagined.

In the early 20th century, animal veins and arteries were used by surgeons to practise suturing and re-joining blood vessels together. In 1912, Alexis Carrel received the Nobel Prize in Medicine or Physiology for his work developing new techniques in suturing blood vessels. These studies laid the foundations for the development of future transplant surgeries.

 
  Alexis Carrel, the future Nobel laureate who pioneered blood vessel sutures, poses for a photo circa 1912.   Popular Science Monthly/Wikimedia Commons . (public domain)

Alexis Carrel, the future Nobel laureate who pioneered blood vessel sutures, poses for a photo circa 1912. Popular Science Monthly/Wikimedia Commons. (public domain)

 

The carnage of World War II advanced modern surgery dramatically. Prior to the war, the complex nature of heart surgery meant it was rarely performed. The sheer mass of casualties during the war forced military doctors to experiment with anaesthesia and suturing techniques. An army surgeon, Dr Dwight Harken, famously managed to remove shrapnel and bullets from the chests and hearts of more than hundreds soldiers without fatality. This unexpected success spurred rapid advances in heart surgery in the post-war era .  

A major barrier to heart surgery was the difficulty of performing long operations. Interrupting cardio-circulatory function for more than a few minutes would result in brain damage. In the 1930s, Carrel collaborated with the famous aviator Charles Lindbergh to invent a machine to circulate vital fluids through excised organs. Using this technique, they kept animal organs and tissues alive for extended periods.

These experiments led to the invention of heart-lung respiratory machines in the 1950s to solve the problem of perfusing the body during heart operations. Early machines were cumbersome and dangerous, leading to damaged blood cells and air embolisms. But eventually these issues were overcome with design improvements, and the first successful open heart operation using cardiopulmonary bypass was performed by Dr John Gibbon Jr in 1953 to repair a heart defect. The patient, Cecelia Bavolek, lived a long life and survived to celebrate the 50th anniversary of that operation in 2003.

Before bypass, open heart surgeries were conducted with cooling treatment and “topical hypothermia”, the chilling of the whole body and the localised hyper-cooling of the heart. This slowed metabolism and therefore slowed damage in the blood-free environment, allowing for adequate time to perform repairs. Hyperthermia approaches became successful in treating minor heart defects.

Doctors and surgeons experimented on animals to hone their skills. Dr Shumway and Dr Lower perfected their transplant technique in dogs for many years before trying a human-to-human heart transplants. In 1958, Dr Shumway successfully transplanted a heart between two dogs. Barnard employed the same technique in the first human-human transplant.

In 1964, a team of US surgeons performed the first animal to human heart transplant. The transplanted a chimpanzee’s heart into the chest of a dying man. It kept beating for 1.5 hours after the surgery, but it was too small to maintain the man’s life. Although it was a failure, it was an important step to realising that human hearts would be required for transplant to be a longer term success. It also raised questions about the ethics of xenographic transplants and outraged animal rights activists.

In 1966, Dr Michael DeBakey implanted a booster pump as an artificial ventricle into a patient, which helped the ailing heart to pump blood whilst waiting for a suitable donor. In 1969, the first temporary artificial heart was implanted a patient who could not be weaned from cardiopulmonary bypass after an extensive procedure. Three days later a donor was found, and a heart transplant operation was performed. 20 years later the first permanent heart, designed by Dr Robert Jarvik, was implanted in 1982. Many patients have received artificial heart transplants, but recipients often suffered from strokes. 

 
  A life-like recreation of Dr Christiaan Barnard's first heart transplant operation, at the Heart of Cape Town Museum.   mallix/Flickr  (CC BY-NC-ND 2.0)

A life-like recreation of Dr Christiaan Barnard's first heart transplant operation, at the Heart of Cape Town Museum. mallix/Flickr (CC BY-NC-ND 2.0)

 

It wasn’t just the surgery that needed to be honed to facilitate the transplant of human hearts. Transplanting organs relies on the understanding of the associated immunology. These advances included the discovery of antibodies and antigens, the development of blood typing, and the understanding of host resistance.

By the mid-20th century, doctors recognised that the immune system was responsible for host rejection of grafts and that treatment with immunosuppressant drugs could delay the rejection of experimental grafts in animals. Early immunosuppressant strategies included steroid injections, azathioprine and radiation treatments. 

In 1954, the first successful human-to-human organ transplant occurred. In Boston, USA, Ronald Herrick donated one of his kidneys to his identical twin brother Richard. Having two kidneys per person and the fact that identical twins are genetically identical made this feat, while impressive, considerably easier than transplanting a heart from a stranger.    

After the first heart transplant

While the first heart transplant was regarded as a surgical success, it was not successful long-term. Washkansky survived the operation, but the potent immunosuppressant drugs used to keep his body from rejecting the transplanted heart weakened his immune system and left him susceptible to infection. Eighteen days after the operation, he died of pneumonia.

Despite this setback, surgeons around the world were inspired and rushed to emulate Dr Barnard's “success.” The next heart transplant, and the first heart transplant in an infant, occurred in the USA just days later, but the patient only lived for six hours.

Some speculate that the rush for progress led to some ethically questionable practices, such as patients being selected as donors with little regard given to their suitability and health or speeding along a donor’s death if they were passing away too slowly. For example, in the first Australian heart transplant in 1968, the removal of the heart from the donor, who had been fatally wounded by a self-inflicted gunshot wound to the head, commenced about three hours after his arrival at hospital. Although blood typing and antigen matching was possible at the time, it took 3 days to have this work done by the Red Cross Blood Service. The doctors decided there was no time to wait. The patient in that case died 40 days later from an opportunistic infection due to the immunosuppressant therapy.

The media in its frenzy also often failed to respect donor confidentiality, with news outlets blithely revealing patient details. The novelty of the procedure also meant that legislation to protect donors and recipients, including definitions of proper death and privacy, often lagged behind the science

In the two years Dr Barnard’s first heart transplant, more than 60 teams had completed the surgery in more than 150 patients, with about 100 of these occurring in 1968. However, stopping the patient’s immune system from rejecting the new heart required large doses of immunosuppressants, leaving them susceptible to deadly infections. About 80% of transplant recipients would die within the first year. It was recognised that this was a major problem, and by 1970 the number of transplants in the year dropped to less than 20.

Continued developments from the 1970s to today

The development of better anti-rejection drugs, advances in tissue typing, tailored immunosuppressant therapy and improved post-operative care in the 1970s improved the viability of heart transplants. By the late 1970s, heart transplant patients were living up to five years after surgery.

 
  Doctors from Australia and Papua New Guinea perform open-heart surgery .   Rocky Roe for AusAID via DFAT/Flickr   (CC BY 2.0)

Doctors from Australia and Papua New Guinea perform open-heart surgery. Rocky Roe for AusAID via DFAT/Flickr (CC BY 2.0)

 

Further improvements to anti-rejection drugs continued into the 1980s and heart transplants became more common. At the end of 2006, more than 74,000 heart and 2,800 heart-lung transplants had occurred around the world. On average, heart transplant can now be expected to last between 10 and 20 years. Some people have more than one heart transplant if the first fails or is rejected. About 85% of patients live for one year, and 60% survive for 10 years or more post-transplant.

In 1984, history was made when Dr Leonard Bailey transplanted a baboon heart into the 12 day old Fae Beauclair, the first infant to receive a cross-species heart transplant. The world watched as “Baby Fae” survived for 20 days before she went into kidney failure and passed away.

Future directions

Recent advances in immunosuppression include the development and more extensive use of antibodies to counteract steroid-resistant rejection. Research is ongoing into the management, treatment and avoidance of accelerated atherosclerosis in the transplanted heart, which is thought to be a side effect of immunosuppressive treatments. Advances in immunology are likely to be the key to expanding the success of heart transplantation. Researchers are also optimistic about alternative therapies such as stem cell treatments, which avoid the need for transplant.

Today, the rising demand and lack of donors mean there is a huge gap between the number of patients requiring hearts and the number available. Research is focused on new approaches to heart transplant. Today, so called bridge-to-transplant operations are routine procedures, with a variety of devices available for use as a circulatory support bridge while waiting for a transplantable organ to become available.

Artificial hearts have become imperative due to the rising number of patients who require a transplant as the supply of donated hearts has not increased accordingly. Research is continuing into the development of effective artificial hearts and ventricular assist devices for transplant candidates either as a long-term solution or as a short-term bridge until they can find a donor. These devices have to potential to improve life-span and quality of life for patients.

Cross species transplants remain contentious for animal ethics reasons, and are difficult due to immunological rejection. However, in 2016, scientists announced that they had kept pig hearts alive and beating in baboons for up to 945 days (more than two and a half years) with the aid of genetic engineering to avoid rejection. With ever expanding genetic engineering techniques, animal transplants may be possible in humans.

The path to our current relative success in heart transplants is paved with success and failure. Many researchers and clinicians laid the foundations that made that first seemingly miraculous transplant possible, and more still have continued to refine the procedures and pre-and post-operative treatment and support in the years since. We can be optimistic that with more research, the situation for those requiring a new heart can only continue to improve.

Edited by Diana Crow