| Abstract |
“The word God is the best abridgement”
Malcolm de Chazal
End stage heart failure: Historical aspects and treatments
Heart failure is a major cause of mortality and morbidity worldwide1. Its treatment consists of medication and surgery2,3. In patients with end stage heart failure the treatment options are limited to cardiac transplantation or implantation of a mechanical circulatory support device. Cardiac transplantation is considered the gold standard treatment4 even though it is accompanied with serious complications. The management of these complications will benefit, however, only the cardiac graft recipients while the improvement of the techniques5 allows the inclusion of more patients in the transplantation program. Nonetheless, for most patients in the heart transplant wait list the cardiac graft will not be found since the donors are scarce. Therefore, the improvement of the mechanical circulatory support devices is the only solution for addressing the needs of the heart patients in the future.
The replacement of the heart and the construction of artificial human parts appear in the ancient mythologies. According to the Chinese myth, the physician Pien Ch’iao put two men to sleep and exchanged their hearts6. In Greek mythology Talos was the legendary guardian of Crete. Built by Hephaestus, the giant, anthropomorphic and mortal Talos lost his life when the ichor that flowed through his bronze body was poured out7. In another myth, Daedalus built artificial wings from feathers and wax to escape with his son Icarus from the Minotaur’s labyrinth.
Apart from the myths, the tooth was the first artificial human part and it was constructed in ancient China. 4,000 years ago, the Chinese placed carved bamboo wood pieces in the jawbone to replace the fallen teeth8-11. The construction of the first artificial finger in ancient Egypt dates to around 800 BC. Tabeketenmut, who was a priest’s daughter, likely suffered from diabetes and lost her toe due to ischemic gangrene. The prosthetic toe fastened with knots of strand and it was made of wood and possibly leather12. In ancient Greece the diviner Hegesistratus, according to Herodotus, was chained by the Spartans and in order to escape he cut his own leg which replaced later
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with a wooden one12. In ancient Rome the general Marcus Sergius, according to Pliny the Elder, lost his arm in battle and then replaced it with an iron one12. Two artificial legs found in Europe date from the 5th and the 8th century AD. One was made of leather and its interior was lined probably with grass or moss while the other was made of wood and bronze12. During the Renaissance came the first artificial limbs with joints13.
The Renaissance was particularly important for the future development of the mechanical circulatory support devices. In 1513, one of the most important scientists of humanity, the genius of Leonardo da Vinci designed artificial valves14. After about a century, in 1628, Harvey first described the pumping action of the heart15. This discovery has corrected the earlier notions of the ancients Greeks on cardiac function. In ancient Greece, Hippocrates had not associated the heart rate with the pulse16. Aristotle believed that the blood was created in the heart and it was absorbed in the periphery17,18. In the Roman Empire, the Greek physician and philosopher Galen made several conclusions. He observed that the heart is muscular and it contracts. He described suction during the cardiac diastole and he understood the function of the valves. However, he considered that the pulse propagates from the arterial wall16. After Harvey overthrew the misconceptions about the heart, in 1812 Le Gallois introduced the idea of mechanical circulatory support19. Today devices that mechanically support the circulation are a reality.
Before the clinical application of the mechanical circulatory support devices, the experimental period was initiated in 1937 when Demikhov implanted an artificial heart into a dog20-22. In 1958 Akutsu and Kolff published the implantation of a pneumatic artificial heart23. In 1962 Liotta implanted in dogs a pneumatic left ventricular assist device that created blood flow from the left atrium into the descending aorta24. In 1965 Nose implanted an artificial heart that kept the animal alive for more than 2 days23. In 1976 an animal lived with the artificial heart Jarvik-5 for 184 days and in 1981 another animal survived for 268 days25-27. During the same period the artificial heart designed by Kwan-Gett was also implanted in laboratory animals23.
The clinical application of the mechanical circulatory support devices was launched in 1969 when Cooley implanted an artificial heart to a patient. This device was designed by Liotta and it was used as a bridge to transplantation, i.e. as a temporary solution until a donor heart was found. But as cardiac grafts were always scarce and some patients are ineligible for transplantation, the use of the artificial heart expanded as a definitive solution. In 1982, DeVries implanted for the first time an artificial heart, the model Jarvic-7, as a definitive solution23.
The circulatory support devices were developed parallel to the development of heart transplantation. After the initial heart transplantation experiments of Carrel and Guthrie in the early 20th
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century, Mann’s experiments followed in the 1930s28 and Demikhov’s in the 1940s29 in Russia. In America during the 1950s Marcus, Wong, Luisada, Webb, Howard, Berman, Akman, Later, Cass and Brock conducted further experiments on the field of heart transplantation4,30. During the same decade, Neptune, Sen and Blanco used hypothermia to transplant the heart and lungs in animals. In 1958, Goldberg made his first orthotopic heart transplantation in a laboratory animal. The experimental heterotopic heart transplantation in the chest was described by Demikhov, Sen, Reemtsma, McGough and Brewer4.
In South Africa in December 1967, Barnard performed the first heart transplantation. The next year 101 heart transplants were performed worldwide but the results were relatively poor. In 1969 47 transplants were performed and during the following years about 25 transplantations were performed annually4. In order to overcome the disadvantages of orthotopic heart transplantation, Barnard developed the heterotopic heart transplantation method experimentally and he applied it clinically for the first time in 19745. This method, whose main feature was the support of the failing heart, proved its advantages.
During the last decades the partial or total mechanical circulatory support is applied in the clinical setting. Total artificial hearts replace the failing heart and take over the circulation. The circulation support devices coexist with the failing heart and provide pulsatile (1st generation) or continuous flow (2nd and 3rd generation), assisting partly to the circulation of blood. Other devices assist the failing heart with aortic counterpulsation, either with an inflatable balloon inside the aortic lumen or by externally compressing the aorta.
Our thoughts and the experiments at the Foundation for Research and Technology
A device that could partially assist the failing heart is the artificial myocardium. Such a device could be placed epicardially and provide external compression to the patient's heart. The method of direct cardiac compression supports the circulation without a blood contacting artificial surface. It does not compromise the myocardial perfusion, although the course of the coronary vessels is epicardial31,32. A direct cardiac compression device is the artificial myocardium made of alloy fibers with shape memory (shape memory alloy – SMA). These fibers contract because of a change in their particular crystalline structure that occurs when an electric current flows through them and heats them. When the cause of the contraction ceases, the fibers are cooled and expand passively.
At the Foundation for Research and Technology a series of experiments were conducted in order to develop artificial myocardium
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made of SMA fibers. Initially a system was built33 that controlled the fibers and their environment, allowing the accurate measurement of the shortening, the electrical resistance, the force and the contraction or expansion velocity at various temperatures. An effective method of controlling the fibers with current shaping was developed and their energetics were studied. A circulatory mockup was built and the pumping action of the artificial myocardium was studied. The artificial myocardium device made of 6 fibers of total weight of about 0.1g produced a maximum stroke volume of 12.67ml and a maximum pressure of about 25mmHg. During the experiments it was found that the fibers expanded slowly and that their effectiveness is limited by the fixed percentage of their shortening. The energy needs of the fibers were studied in each experimental stage and it was deduced that the energy efficiency is about 0.3%. The power of the artificial myocardium was estimated approximately 9.7watt.
The major disadvantage of the SMA fibers is the low diastolic velocity. To accelerate their diastole, cooling agents were used with good results and an increase of their energy requirements. The braids that were made of SMA fibers achieved faster relaxation than the equivalent single fibers. To increase the displacement a system was built with sliding boards that multiplied the displacement by 6 times without reducing the force. The contractible cycle that was also constructed could transform the shortening of the fibers at its periphery to centripetal compression, according to a constantly changing conversion rate.
Conclusions
The advantages of supporting a failing heart with direct cardiac compression outweigh the low efficiency of the artificial myocardium made of SMA fibers. The fibers can be controlled optimally and their pumping action is good. The methods for increasing the diastolic velocity and the displacement were effective but additional research needs to be performed to develop a clinically useful device. The ultimate goal is to design circulatory support devices that could be considered equivalent or superior to heart transplantation.
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Ενεργειακή διερεύνηση και προσομοίωση της μηχανικής υποστήριξης της ανεπαρκούσης καρδιάς με αποδοτικό σύστημα
