This article is reproduced from WeChat WeChat official account: Medical circles., by Yan Xiaoliu.
"Since the heart can grow, it will certainly be made."
On the second day after the "artificial heart" was implanted, Mr. A, 42, got out of bed and moved. Previously, he was bedridden for many years due to illness, and he had to rely on people to help him eat and bathe.
"His recovery is ideal. The ventilator was withdrawn on the first day after surgery. " Recently, Huang Keli, one of the chief surgeons and director of the Heart Surgery Center of Sichuan Provincial People’s Hospital, told the medical community that Mr. A had dilated cardiomyopathy and was in end-stage heart failure.(hereinafter referred to as heart failure). The attending doctor put it on the waiting list for heart transplantation. However, according to its existing heart function, the life expectancy is less than one year. "I’m afraid I can’t wait for the day of transplantation."
Mr. a’s angiography after artificial heart implantation. /Photo courtesy of Sichuan Provincial People’s Hospital
The heart is the "engine" of the human body, the atrium is responsible for the whole body blood return, and the ventricle is responsible for pumping blood. End-stage heart failure means that this "engine" is so worn out that it can’t be repaired and may turn off at any time. Almost all heart diseases continue to deteriorate and eventually progress to heart failure.
On December 3, 1967, in Cape Town, South Africa, 45-year-old surgeon Christian Bernard.（Christiaan Barnard）Complete the world’s first human heart transplant. A heart of a 25-year-old woman who died in a car accident was implanted in the chest of a 55-year-old man with severe heart failure. Although the male patient died of pneumonia 18 days after the operation, it opened a new era, and the medical community began to try to "exchange hearts for hearts".
However, this treatment mode is doomed to be a drop in the bucket. The high cost of surgery and post-maintenance is one aspect. The number of donors and the matching degree are another hurdle for the transplant recipients. In addition, the heart has the shortest preservation time among all transplanted organs. The taken heart is allowed to warm ischemia for only 3-4 minutes, and can only be preserved for 6-8 hours at a suitable temperature. This significantly increases the difficulty of transplantation.
According to China Cardiovascular Health and Disease Report 2019, according to the prevalence of cardiovascular diseases in China, the number of patients with heart failure in China is about 8.9 million, and the number of patients with advanced heart failure is nearly 1 million. The number of heart donors in China can’t meet the requirements of heart transplantation in China. The data shows that in 2015-2018, there were 35 nationwide.(excluding Hong Kong, Macao and Taiwan)Since the full implementation of brain-dead heart donation in the heart transplantation center, 1583 cases of heart transplantation have been completed.
Huang Keli said with regret: "We have already met two or three patients who are in urgent need of heart transplantation, and they regret to die because they can’t wait for a donor."
Only the "very few" who have saved the Milky Way in their previous lives can get this extremely scarce resource and be reborn. And a universal artificial heart that can temporarily or permanently play a substitution role has become the best choice for patients with end-stage heart failure.
Professor Christian Bernard became famous for successfully completing the world’s first heart transplant. /Getty Images
Artificial heart is not like "heart"
Artificial heart is not a new word. In ancient Greek mythology, "Death" Thanatos had an iron core and a copper heart. The absolute protagonist "Iron Man" who saved the modern world is also an immortal superhero created by artificial heart.
Modern medicine defines an artificial heart as a ventricular assist device/system that partially or completely replaces the pumping function of the heart to maintain the whole body blood circulation by biomechanical means. In 2013, the American Heart Association（AHA）In the management guide of heart failure, ventricular assist device is listed as one of the optional treatment schemes.
Based on human body structure, ventricular assist devices can be divided into left ventricular assist and right ventricular assist. The device that acts on both ventricles at the same time is described as "total artificial heart" by the medical community.
"From the global situation, from June 2006 to July 2018, nearly 25,000 patients received ventricular assist device implantation." Professor Zhou Jianye, deputy director of the Key Laboratory of Regenerative Medicine of Fuwai Hospital of China Academy of Medical Sciences, once told The Paper that there are three main clinical applications of artificial heart, as a transition to waiting for heart transplantation, to win more time for patients to wait for suitable donors; Provide short-term replacement support for patients with acute heart failure, and remove it after cardiac function is restored; To provide long-term replacement for patients with end-stage heart failure and support patients to carry artificial hearts for long-term survival.
In Sichuan Provincial People’s Hospital, after multidisciplinary evaluation by the Heart Center, Huang Keli and his team installed the third generation artificial heart for Mr. A. Its core components include an external controller shaped like a backpack, and a metal blood pump like a water pipe tee, which is half the size of a fist.
Image source: Photo courtesy of Sichuan Provincial People’s Hospital
"The heart is like a pump, which contracts and relaxes day and night to provide power for blood circulation. The purpose of artificial heart is to build an auxiliary flow channel of the heart and help realize blood circulation. The blood pump is connected with the patient’s own heart by two artificial blood vessels. Blood flows from the ventricle through blood vessels and into the blood pump. The impeller in the blood pump rotates to generate centrifugal force, which pumps the blood out and flows into the ascending aorta through the outflow vessel, partially or completely replacing the heart function. " Huang Keli explained.
The blood pump is connected to the controller outside the body through a pump cable, and the patient needs to carry it with him. Huang Keli introduced that the controller weighs about 3kg and has a battery pack and a speed control system to provide power.
The "medical field" found that the first and second generation artificial hearts were pulsatile pumps and axial pumps respectively. The first generation of pulsatile artificial heart, also known as positive displacement pump, is bulky and difficult to implant. The volume of the second generation artificial heart becomes smaller, but the impeller speed is high, which may damage red blood cells and coagulation system and easily cause thrombosis.
Huang Keli said that the equipment of the third-generation artificial heart is small in size, easy to implant, and generates almost no heat during operation. Because of the non-contact bearing, the core parts can rotate without any mechanical contact with the surrounding components, which reduces the loss caused by mechanical friction. Because the core parts are not in direct contact with blood, the thrombus problem is also obviously improved.
It also has some problems, such as high cost, inconvenient carrying, high energy consumption, limited battery life and easy to be affected by external magnetic fields.
"The implanted artificial heart can continue to work until a heart transplant is performed. In addition to not being able to swim, patients can live like normal people, walking, showering, working normally and traveling. " Huang Keli told the "medical community" that the first patient in the clinical trial of artificial heart in China has been living with the machine for 3 years. And Mr. A also set a record, which is the first artificial heart officially listed in China.(Left ventricular assist system)Implant surgery patients.
R&D road: full of hardships, not smooth road.
"Since the heart can grow, it will certainly be made." This is William John kolff, the "father of artificial organs" and the pioneer of artificial heart.（Willem Johan Kolff）What I said.
In 1957, kolff and the 35-year-old Japanese scholar Akitsu Tetsuo.（Tetsuzo Akutsu）Cooperate to develop the world’s first artificial heart. In his manuscript, Akujin said that the idea of research and development began with the imitation of the human heart. "In any case, it is necessary to make the artificial look exactly like the real heart." He filled the office with machine tools, kneaded clay, watered gypsum and cut metal. He works day and night, making all the parts by hand. Finally, the finished product comes out, which looks like a real heart and has four chambers, including left atrium, left ventricle, right atrium and right ventricle. Pulsating flow is generated by using circulating hydraulic pressure.
William John kolff (left) and Tetsuo Akujin. /Cleveland Clinic
December 12, 1957(It is also said that it was January 1958)With the support of cardiopulmonary bypass, kolff and Ajujin implanted their artificial heart into experimental dogs. After the termination of cardiopulmonary bypass, the artificial heart continued to maintain blood circulation for 90 minutes. In 1958, the relevant experimental results were reported at the fourth meeting of the American Artificial Organ Association.
Since then, more and more research teams around the world have tried artificial hearts.
In 1969, the United States completed the world’s first biventricular assist device implantation. Denton Arthur Cooley, American doctor（Denton Arthur Cooley）For a 47-year-old man, the "Liotta-Cooley Total Artificial Heart" named after him was implanted.(Liotta-Cooley artificial heart)As a transitional treatment before heart transplantation. This is a pneumatic "artificial heart". With the help of external power, the patient lived on it for 64 hours and then received a heart transplant. 32 hours after heart transplantation, the patient died of Pseudomonas pneumonia.
The second case of artificial heart implantation occurred more than 10 years later. In 1981, the surgeon was still Cooley, and the device was an upgraded version with two pneumatic biventricular pumps.(Akutsu-Ⅲ artificial heart). 55 hours after implantation, the patient received a heart transplant. Ten days after operation, the patient died of infection, renal failure and pulmonary complications.
These two artificial hearts used by Cooley have not been used in clinic.
The picture comes from the Internet.
In 1970, the University of Utah introduced Jarvik-7 artificial heart, which is still a pneumatic biventricular pump. On December 2, 1982, the device was first placed in a 61-year-old patient with heart failure. The patient died 112 days after operation. From 1985 to 1991, about 170 patients used Jarvik-7 as a transitional treatment before heart transplantation. During this period, the incidence of sepsis and multiple organ failure was high. In 1991, the US Food and Drug Administration（FDA）Stop the clinical application of the device on the grounds that it does not meet the FDA management terms.
After 1990s, Jarvik-7 was innovated and renamed, and was successfully applied in clinic in the United States, Canada and France in 2001. In 2004, FDA approved it as an adjuvant treatment before transplantation. In March 2012, the FDA of the United States used "humanitarian use equipment"（HUD）",approved as the endpoint treatment. HUD is set up for special medical devices, especially those designed to serve a few special patients, which affect less than 8,000 people every year in the United States, and bring benefits that outweigh the possible injury or disease risks caused by use.
In 2000, the world’s first fully-built artificial heart came out, including electric pump system.(including 2 artificial ventricles and 4 valves)Control system, battery and transcutaneous energy transmission system（TET）Coil. The electric pump placed in the body passes through TETAnd radio frequency AC system for charging and signal transmission. Because there is no pipeline penetrating the chest wall, the risk of infection of patients is greatly reduced. However, this device is bulky and weighs 900g, which is only suitable for patients with large chest volume. It has not been approved by FDA for more than 20 years.
"The road to research and development of total artificial heart is full of hardships and needs to overcome many difficulties. Due to serious complications such as infection, bleeding, thromboembolism and biocompatibility after early implantation, the patient died, and many clinical trials of total artificial heart projects were forced to stop. " In 2014, Hu Shengshou, academician of China Academy of Engineering and dean of Fuwai Hospital of China Academy of Medical Sciences, wrote in How Far Is Total Artificial Heart from Us? "wrote.
As a result, some researchers who are committed to the research and development of total artificial heart, such as Akujin, turned to single ventricular assist devices.
Huang Keli said that the left ventricle is the main power source for pumping blood to the whole body. In many severe cases of heart failure, if the left ventricular problem can be solved, enough cardiac function can be provided.
Clinical trials have also found that some patients who use left ventricular assist devices eventually recover to the point where they can live on the original heart without an assist device. The reason is that their overwhelmed myocardium, with the help of cardiac AIDS, gets precious breathing time and finally regains strength. This also saves it from heart transplantation. "After transplantation, patients need long-term and high-dose anti-rejection drugs. This may cause damage to liver and kidney function and increase the risk of malignant tumors. " Huang Keli said that when the ventricular assist device is implanted, the drugs used by patients are much simpler, mainly anticoagulation.
The data show that the left ventricular assist device implanted by Mr. A has been worn by patients abroad for 10.5 years.
In June 2016, 25-year-old American guy Stan Larkin was widely concerned by the media. He lived for 555 days by using a biventricular assist device, and finally waited for a heart transplant. /Daily Mail
Judging from the current situation of technical development, in order to permanently replace the human heart, cardiac auxiliary devices have to overcome many technical difficulties. Including: low anticoagulation or non-anticoagulation, less power requirements, quieter, easy to implant and monitor, longer battery life, no parts outside the body. Eventually, they should become "implanted and forgotten" devices.
At present, the combination of artificial heart and regenerative medicine has become one of the mainstream research directions. For example, cells are extracted from patients’ leg muscles, cultured and made into sheets, and then implanted into patients’ hearts together with artificial hearts. Cells will work with the heart muscle. Once the heart function is strong enough, the artificial heart can be taken out and the patient will live on his own heart.
The dreams of the pioneers are gradually being realized by later generations.