The Artificial Heart
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《新英格兰医药杂志》
At 10:30 p.m. on December 1, 1982, a retired dentist named Barney Clark was wheeled into an operating room at the University of Utah Medical Center in Salt Lake City. Clark, who was 61 years old, had end-stage congestive heart failure. When his condition acutely worsened that night in the middle of a heavy snowstorm, his doctors decided to press ahead with the world's first implantation of a permanent artificial heart. By the time the seven-hour operation was over, it had unleashed a blizzard of a different kind.
By all accounts, when Clark was hospitalized in late November, he was at the end of his life. For months, he had had virtually intolerable shortness of breath, nausea, and fatigue. On Thanksgiving Day, family members had to carry him to the dinner table at his home in Seattle, but he was unable to eat. In the intensive care unit in Salt Lake City, he was placed in a dark room, and visitation was restricted because doctors feared that any sort of excitement could precipitate a life-threatening arrhythmia. In the words of William DeVries, the lead surgeon, and his colleagues, whose landmark report appeared 20 years ago this week in the Journal,1 "death appeared imminent within hours to days."
Because of his age and severe emphysema, Clark was not eligible for a heart transplant. When his doctors brought up the option of an artificial heart, Clark visited a laboratory at the University of Utah where calves had been kept alive for months with a Jarvik-7 device (see Figure). The aluminum-and-polyurethane organ had two separate ventricles grafted with Dacron sleeves to the native atria and great vessels and was powered by an air compressor that weighed almost 400 pounds. The sight must have disturbed Clark, because he told his doctors that he would take his chances with medical therapy. But worsening heart failure forced him to reconsider, and so in the early morning of December 2, Clark came out of the operating room with plastic tubes coming out of his chest, connected to a refrigerator-sized machine. Though he was very much alive, his electrocardiogram was a flat line.
Figure. The Jarvik-7 Artificial Heart (Left) and the AbioCor Artificial Heart (Right).
The Jarvik-7 was the product of several decades of research. The first artificial heart implanted in a living being was placed in a dog at the Cleveland Clinic in 1957; it survived about 90 minutes. In 1964, the National Institutes of Health started the Artificial Heart Program, with the goal of putting a man-made organ into a human by the end of the decade. This milestone was achieved in 1969, when Denton Cooley, a surgeon at the Texas Heart Institute in Houston, used an artificial heart as a bridge to transplantation in a 47-year-old man. The patient survived for about three days but died shortly after heart transplantation. Thirteen years elapsed before the first attempt was made to use an artificial heart for long-term or "destination" therapy.
DeVries and his colleagues could not have anticipated the intense worldwide interest in their experiment. Teams of reporters and television crews swarmed the medical center, hankering for information about Clark's condition, even sneaking into the intensive care unit to check on him. The hospital cafeteria was transformed into a virtual press club, with hospital spokespeople providing twice-daily briefings. Clark's private struggle quickly became a public spectacle.
Although he opened his eyes and moved his limbs three hours after the operation, his subsequent course was rocky. On day 3, he underwent thoracic exploratory surgery because of subcutaneous emphysema. On day 6, he had generalized seizures that left him in a postictal coma. On day 13, his prosthetic mitral valve malfunctioned, and he had to go back to the operating room to have the left ventricle replaced. Many complications followed, including respiratory failure requiring a tracheostomy, renal failure, rampant fevers, aspiration pneumonia, pseudomembranous colitis, and sepsis. On day 92, DeVries spoke with Clark in a videotaped interview. "It's been hard, hasn't it, Barney?" DeVries said. "Yes, it's been hard," Clark replied. "But the heart itself is pumping right along." It continued to pump until he finally succumbed to multiorgan failure on day 112.
Clark's Jarvik-7 became medicine's Sputnik; never before had a medical innovation sparked such furious debate, even a kind of national reckoning. Though some doctors viewed the experiment as successful, most people were deeply disturbed by what they had witnessed. For some, the human heart had special spiritual and emotional meanings that made it impossible to replace with a man-made device. Una Loy, Clark's wife, voiced this belief when she asked, "Will he still be able to love me?" Others were troubled by the fact that Clark had never left the hospital. He had survived for almost four months, they said. But had he really lived?
After Clark died, there was a period of public disenchantment with artificial organs. The New York Times dubbed artificial-heart research a kind of "Dracula" that was sucking money away from more worthwhile programs. By the latter part of the decade, artificial hearts were being used almost exclusively as bridge therapy. In 1990, the Food and Drug Administration (FDA) issued a moratorium on the use of the Jarvik-7 device.
Although research began to focus on ventricular-assist devices, work continued on a permanent artificial heart. On July 2, 2001, the first fully contained artificial heart was implanted in a 58-year-old man at Jewish Hospital in Louisville, Kentucky. The hydraulically powered device, called AbioCor (see Figure) and designed by a company called Abiomed, was about the size of a grapefruit and had a battery that could be recharged through intact skin, obviating the need for external power lines. The patient lived for five months before dying from a stroke.
A phase 1 trial of the device is still under way at six medical centers in the United States. So far, nine patients have received the heart and have survived with it for an average of about five months. (One patient lived for 17 months and was able to leave the hospital.) A spokeswoman for Abiomed says it is hoping to start marketing the AbioCor with an investigational-device exemption from the FDA by the end of 2004.
Despite progress in the development of an artificial heart, the workhorse of mechanical support for patients with heart failure today is the left ventricular assist device, which piggybacks onto the native heart, pumping blood directly out of the left ventricle and into the aorta. Approved by the FDA for both destination and bridge therapy, these devices have become a lifesaving option for thousands of patients. Although approximately 100,000 patients in the United States could potentially benefit from heart transplantation, only 2000 donor hearts become available every year. So far, according to industry experts, about 7000 left ventricular assist devices have been implanted worldwide. Some patients have had full recovery of ventricular function with these devices, though the mechanisms remain unclear.
Unfortunately, left ventricular assist devices are still not a therapeutic option for patients with severe biventricular failure. For these patients, like Clark, a permanent artificial heart may be the best hope. For now, it remains a dream — infections and thromboembolism are still major obstacles — but not quite the pipe dream it was in 1982, when a soft-spoken dentist from Seattle decided to go first.
Source Information
From New York University Medical Center, New York.
References
DeVries WC, Anderson JL, Joyce LD, et al. Clinical use of the total artificial heart. N Engl J Med 1984;310:273-278.(Sandeep Jauhar, M.D., Ph.)
By all accounts, when Clark was hospitalized in late November, he was at the end of his life. For months, he had had virtually intolerable shortness of breath, nausea, and fatigue. On Thanksgiving Day, family members had to carry him to the dinner table at his home in Seattle, but he was unable to eat. In the intensive care unit in Salt Lake City, he was placed in a dark room, and visitation was restricted because doctors feared that any sort of excitement could precipitate a life-threatening arrhythmia. In the words of William DeVries, the lead surgeon, and his colleagues, whose landmark report appeared 20 years ago this week in the Journal,1 "death appeared imminent within hours to days."
Because of his age and severe emphysema, Clark was not eligible for a heart transplant. When his doctors brought up the option of an artificial heart, Clark visited a laboratory at the University of Utah where calves had been kept alive for months with a Jarvik-7 device (see Figure). The aluminum-and-polyurethane organ had two separate ventricles grafted with Dacron sleeves to the native atria and great vessels and was powered by an air compressor that weighed almost 400 pounds. The sight must have disturbed Clark, because he told his doctors that he would take his chances with medical therapy. But worsening heart failure forced him to reconsider, and so in the early morning of December 2, Clark came out of the operating room with plastic tubes coming out of his chest, connected to a refrigerator-sized machine. Though he was very much alive, his electrocardiogram was a flat line.
Figure. The Jarvik-7 Artificial Heart (Left) and the AbioCor Artificial Heart (Right).
The Jarvik-7 was the product of several decades of research. The first artificial heart implanted in a living being was placed in a dog at the Cleveland Clinic in 1957; it survived about 90 minutes. In 1964, the National Institutes of Health started the Artificial Heart Program, with the goal of putting a man-made organ into a human by the end of the decade. This milestone was achieved in 1969, when Denton Cooley, a surgeon at the Texas Heart Institute in Houston, used an artificial heart as a bridge to transplantation in a 47-year-old man. The patient survived for about three days but died shortly after heart transplantation. Thirteen years elapsed before the first attempt was made to use an artificial heart for long-term or "destination" therapy.
DeVries and his colleagues could not have anticipated the intense worldwide interest in their experiment. Teams of reporters and television crews swarmed the medical center, hankering for information about Clark's condition, even sneaking into the intensive care unit to check on him. The hospital cafeteria was transformed into a virtual press club, with hospital spokespeople providing twice-daily briefings. Clark's private struggle quickly became a public spectacle.
Although he opened his eyes and moved his limbs three hours after the operation, his subsequent course was rocky. On day 3, he underwent thoracic exploratory surgery because of subcutaneous emphysema. On day 6, he had generalized seizures that left him in a postictal coma. On day 13, his prosthetic mitral valve malfunctioned, and he had to go back to the operating room to have the left ventricle replaced. Many complications followed, including respiratory failure requiring a tracheostomy, renal failure, rampant fevers, aspiration pneumonia, pseudomembranous colitis, and sepsis. On day 92, DeVries spoke with Clark in a videotaped interview. "It's been hard, hasn't it, Barney?" DeVries said. "Yes, it's been hard," Clark replied. "But the heart itself is pumping right along." It continued to pump until he finally succumbed to multiorgan failure on day 112.
Clark's Jarvik-7 became medicine's Sputnik; never before had a medical innovation sparked such furious debate, even a kind of national reckoning. Though some doctors viewed the experiment as successful, most people were deeply disturbed by what they had witnessed. For some, the human heart had special spiritual and emotional meanings that made it impossible to replace with a man-made device. Una Loy, Clark's wife, voiced this belief when she asked, "Will he still be able to love me?" Others were troubled by the fact that Clark had never left the hospital. He had survived for almost four months, they said. But had he really lived?
After Clark died, there was a period of public disenchantment with artificial organs. The New York Times dubbed artificial-heart research a kind of "Dracula" that was sucking money away from more worthwhile programs. By the latter part of the decade, artificial hearts were being used almost exclusively as bridge therapy. In 1990, the Food and Drug Administration (FDA) issued a moratorium on the use of the Jarvik-7 device.
Although research began to focus on ventricular-assist devices, work continued on a permanent artificial heart. On July 2, 2001, the first fully contained artificial heart was implanted in a 58-year-old man at Jewish Hospital in Louisville, Kentucky. The hydraulically powered device, called AbioCor (see Figure) and designed by a company called Abiomed, was about the size of a grapefruit and had a battery that could be recharged through intact skin, obviating the need for external power lines. The patient lived for five months before dying from a stroke.
A phase 1 trial of the device is still under way at six medical centers in the United States. So far, nine patients have received the heart and have survived with it for an average of about five months. (One patient lived for 17 months and was able to leave the hospital.) A spokeswoman for Abiomed says it is hoping to start marketing the AbioCor with an investigational-device exemption from the FDA by the end of 2004.
Despite progress in the development of an artificial heart, the workhorse of mechanical support for patients with heart failure today is the left ventricular assist device, which piggybacks onto the native heart, pumping blood directly out of the left ventricle and into the aorta. Approved by the FDA for both destination and bridge therapy, these devices have become a lifesaving option for thousands of patients. Although approximately 100,000 patients in the United States could potentially benefit from heart transplantation, only 2000 donor hearts become available every year. So far, according to industry experts, about 7000 left ventricular assist devices have been implanted worldwide. Some patients have had full recovery of ventricular function with these devices, though the mechanisms remain unclear.
Unfortunately, left ventricular assist devices are still not a therapeutic option for patients with severe biventricular failure. For these patients, like Clark, a permanent artificial heart may be the best hope. For now, it remains a dream — infections and thromboembolism are still major obstacles — but not quite the pipe dream it was in 1982, when a soft-spoken dentist from Seattle decided to go first.
Source Information
From New York University Medical Center, New York.
References
DeVries WC, Anderson JL, Joyce LD, et al. Clinical use of the total artificial heart. N Engl J Med 1984;310:273-278.(Sandeep Jauhar, M.D., Ph.)