Denton Cooley

DR. DENTON COOLEY, WHO WAS one of the physicians working toward successful heart transplantation in the late 1960s, vividly remembers the excitement at the dawn of heart transplantation:

"Many of us in the United States, maybe four or Jive surgeons that I know of, were challenged by the idea of a heart transplant. I'm not sure what stopped the others. But what delayed me was trying to identify a donor. I could not quite understand how we were going to get a good donor heart"

In 1968 and 1969, with those hurdles overcome, Cooley performed twenty-two heart transplants.

"Nothing for me could compare with the excitement of that first cardiac transplantation I did in 1968," he said in a recent interview. "It was very thrilling, but I felt a lot of pressure. I've never been more exhilarated than I was to see that heart begin to work and see the patient recover."

Although Cooley was at the very cutting edge of early transplantation, the first human-to-human heart transplantation was performed by another doctor, who shouldered the immense responsibility of showing that the concept was practical. "It is to Dr. Christiaan Barnard's enduring credit that he showed a beating human heart could be removed from one individual and implanted into another," Cooley said. "Prior to that, we weren't quite certain of the ethics of taking out a beating heart because in those days, we always thought that life continued until the heart stopped beating. We didn't quite understand the fact that sometimes with brain injuries, the heart would keep working long after the patient was clinically dead."

Since that first transplant, technology and medicine have made great leaps in the treatment of failing hearts, including ventricular assist devices, pacemakers, and defibrillators. Said Cooley:

"If we had the donors, I think we would be able to forget about the mechanical replacement of the heart. But we're never going to have enough donors to meet the need. So we have to have some mechanical support devices, although many of these devices will be used as a bridge to transplantation."

Dr. Denton Cooley performed twenty-two heart transplantations in 1968 and 1969, making him the most prolific transplantation surgeon in the world at that time.

Dr. Willem Kolff was a true pioneer in artificial organ technology. His models for artificial hearts inspired the original Jarvik hearts that were implanted into human patients in the mid-1980s.

The Mechanical Heart

AFTER THE HEART-LUNG MAchine had proved that people could live while being supported by a machine, it was a short and logical jump to a completely artificial heart. Working first at the Cleveland Clinic and later at the University of Utah, Dr. Willem Kolff became one of the leading doctors in the development of artificial hearts and other organs. Kolff, in fact, had invented the artificial kidney in the 1940s in Nazi-occupied Holland.

"I went to Berk EnamelWorks and spoke to Mr. Berk and explained the principal of the rotating drum artificial kidney to him," Kolff recently remembered about that first artificial kidney.

"Berk EnamelWorks began making artificial kidneys for me. When it came time to pay, it turned out they were only allowed to work for the German Wermacht, that is, the German army, so I never got a bill. We would, of course, have gone to concentration camps if we had."

Kolff used fifteen artificial kidneys during the war, and this invention went on to provide long-term benefits for thousands of patients. Like a real kidney, the artificial kidney is connected to the patient's circulation, except that it is done through small tubes. When blood flows through the machine, it cleanses the blood of the waste products that by a group including Kolff, Dr. William DeVries, and Dr. Robert Jarvik at the University of Utah in 1982. By 1985, they had implanted the Jarvik heart in four patients, and one survived for 620 days after implantation. The Jarvik-7 heart was based on long-standing research by Kolff and his team at the University of Utah and earlier at the Cleveland Clinic.

All of these mechanical artificial heart devices required tubes running through the skin to an external power source and drive unit. Although the machines that powered the hearts were external and relatively large, they also had smaller portable drive units so patients could get up and walk around.

Over time, all of their patients suffered complications related to their artificial hearts, including blood clots and infections, which are particularly prone to occur with these types of devices. Any device that breaks the skin's natural barrier poses a danger of infection because the skin is such an effective barrier against bacteria. When tubes and wires go through the skin, bacteria can eventually get into the body and infect these devices.

One of the patients who had such a device — Barney Clark — became somewhat of a celebrity. His device functioned for more than a year. One might consider these short-lived clinical research trials as failures. Nevertheless, much important information was learned and shared from having these devices in humans (as opposed to animals). At the University of Utah and other centers, laboratory research continues on various types of artificial hearts and ventricular assist devices.

Currently, however, there are no permanent, implantable artificial hearts being placed in humans worldwide.

Ventricular Assist Devices

Short of a totally artificial heart, the FDA has approved devices that are designed to help the heart's ventricles pump blood, called ventricular assist devices (Fig. 11.3). In most cases, these devices are used only as a bridge to heart

The Jarvik 2000, a left ventricular assist device, is used to aid a failing left ventricle. It is thumb-sized. The controller and battery are the size of a portable telephone and worn externally.

transplantation and usually remain implanted for a few days up to several weeks. However, some patients have had these ventricular assist devices for more than a year.

When the devices are used as a bridge to heart transplantation, the results are good. The devices do not appear to affect long-term survival after heart transplantation, which is about the same in patients who needed the devices as in those who did not.

At some centers in Europe, ventricular assist devices are being implanted in patients who are not being considered for heart transplantation. Doctors are hoping that the sick heart will recover during several months, at which point the device can be removed. So far, however, it's been found that most of these patients do not recover enough to allow the devices to be removed.

One major drawback of the assist device is that it requires tubes that run through the skin to external power sources. Portable machines allow the the patient's own kidneys would normally remove. Renal dialysis, or mechanical blood cleansing, is now used all over the world to treat patients with kidney failure and is based on concepts initially developed by Kolff. In fact, Kolff estimates that approximately half a million people in the United States alone are treated each year with renal dialysis.

After the war was over, Kolff moved to the Cleveland Clinic, where he began researching the heart-lung machine and artificial hearts. In 1957, he and a colleague, Dr. Tetsuzo Akutsu, removed the heart from a dog and implanted the first artificial heart, which kept the dog alive for ninety minutes with its circulation totally supported by the device. Although the device was implanted, tubes ran through the skin to the power source.

Soon after this, Kolff moved to the University of Utah, where he began to build an artificial organ program. It was in this program and under Kolffs leadership that Dr. Robert Jarvik began his research into the artificial heart that would later bear his name and be implanted into Barney Clark in 1982.

"Although it was not a clinical success, the procedure was an important milestone," remembered Kolff. "We knew from animals that we could sustain the circulation, but from Barney Clark, we learned that he still loved his family, that his mind was okay, that his sense of humor was okay, that he still wanted to serve his fellow man. All of the important things were retained."

The Jarvik 2000, a left ventricular assist device, is used to aid a failing left ventricle. It is thumb-sized. The controller and battery are the size of a portable telephone and worn externally.

patients to be fairly active or mobile so they can improve their physical condition over time. Unfortunately, infection often occurs over time with this type of device because of

During the Batista procedure, a portion of the enlarged left ventricle (A) is removed (B), and the remaining muscle is sewn back together (C).

Enlarged Left Ventricle

the tubes and wires that have to cross the skin barrier.

Patients who are having mechanical assist devices implanted on a permanent basis should consider this as clinical research. It's likely that with time and research, there will eventually be assist devices and artificial hearts commonly available at all hospitals where heart surgery is performed. Some will most likely be totally implantable so no tubes or wires will cross the skin. The surgery done to implant these devices will become routine.

Batista Procedure

Dr. Randas Batista, a heart surgeon in Brazil, has recently developed a heart surgery procedure for certain patients with substantially enlarged, failing hearts. In the Batista procedure, the doctor removes a piece of the enlarged left ventricle and sews the remaining edges of the cavity back together (Fig. 11.4). After the size of the chamber is reduced, the left ventricle seems to function better and more efficiently. Batista has often found, however, that he has to either repair or replace the mitral valve because part of the muscle that controls it frequently has to be removed as part of the procedure.

The early mortality for this procedure, both in Brazil and in centers in this country, has been about 20 percent. By about

two years after the procedure, about 40 percent to 50 percent of the patients die; however, some of the patients who survive the procedure seem to do quite well and are relieved of their symptoms of heart failure for at least two years after the procedure. At this point, it is unclear how these patients will do long term or if the heart will expand again.

More information needs to be obtained, particularly from long-term follow-up, before this operation can be recommended as a routine form of surgery for treating patients with considerable heart failure.

Skeletal Muscle Cardiac Assist

The final form of heart assist involves neither mechanical devices nor donated organs but uses part of the patient's own anatomy to bolster the heart's function. This approach was pioneered in animals by Kantrowitz in 1959 when he wrapped the diaphragm muscle around the heart and stimulated the muscle to contract in synchrony with the animal's heart. This worked, but only for several seconds until the muscle fatigued.

The problem of muscle fatigue was solved in 1969 when Drs. Stanley Salmons and Greta Vrbova from London, England, discovered that certain types of skeletal muscles, which are attached to the bones in our arms, legs, and elsewhere, could be electrically conditioned and made more fatigue resistant.

This observation led me and colleagues at the University of Pennsylvania to develop an electrical conditioning protocol for fiber transformation of animal muscles. Meanwhile, Dr. Ray Chiu and associates at McGill University developed the concept of burst stimulation to increase the force of muscle contraction.

These advances in muscle conditioning prompted several surgeons to wrap the back muscle, or latissimus dorsi, around the failing ventricles and stimulate the muscle to contract during contraction of the heart muscle. This procedure, which is known as cardiomyoplasty, was first performed in a human by Dr. Alain Carpentier in 1985.

Cardiomyoplasty:

A surgical procedure using a muscle, usually the latissimus dorsi muscle in the back, to wrap around a failing heart. The muscle is then electrically stimulated so it will contract in synchrony with the failing heart and hopefully improve the signs and symptoms of heart failure.

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