Originally published in Volume 36 Issue 1 of Artificial Organs, 18 January 2012
The University of Minnesota played a chief role in the development of modern heart surgery. It was there that Dr. Walton Lillehei carried out the first procedure with cross circulation. In 1955, he started using extracorporeal circulation (ECC) with the help of an oxygenator developed in association with Dr. Richard de Wall and a roller pump introduced by Michael DeBakey. By 1956, they had performed 80 surgical procedures using the bubble oxygenator.
Minnesota became a Mecca for thoracic surgeons from all over the world and opened its doors and expertise to hundreds of them. Dr. Lillehei is known to have trained around 1000 surgeons, among them Dr. Christian Barnard and Dr. Norman Shumway, pioneers in the heart transplant technique. Several Brazilian surgeons have been to Minnesota. One of them, Dr. Hugo Felipozzi, was there in 1954. Back to Brazil, in 1956, he carried out Brazil’s first surgery with ECC using the techniques and equipment developed in the USA, later adapted and manufactured in Brazil. Bizarrely, he built his equipment in an institute for heart studies funded by a large cigarette factory owned by his in-laws.
Another Brazilian surgeon, Dr. E.J. Zerbini (Fig. 1), went to Minnesota in 1957 with support of the Rockefeller Foundation. He had already been in the USA for specialization with a grant from the US State Department. Back in Brazil, he carried out in 1958 his first surgery with ECC repairing an atrial septal communication at the University of São Paulo Hospital using equipment built by himself and his assistants within the hospital building.
Figure 1
Zerbini was a very active man, and as Lillehei, he was devoted to the task of teaching. He organized an itinerant surgical team, and visited several capital cities within Brazil and South America to teach heart surgery with ECC. His equipment was carried in 60 heavy crates aboard a twin engine C-47 that crossed the Andes many times. By 1964, he had performed 1000 surgical procedures using ECC. A very enterprising man, he improvised a machine shop within the hospital grounds building the equipment that was used. He employed modern-minded and versatile engineers in the newly established Instituto Tecnológico da Aeronáutica, a high-level aeronautical engineering school, planned by Dr. Richard H. Smith, from the Massachusetts Institute of Technology. Very soon, all equipment required for ECC was being manufactured in São Paulo in a regular fashion.
The well-trained doctors and engineers working under Zerbini’s dynamic leadership explain how during the 1960s ECC pumps, oxygenators, prosthetic heart valves, electrocardiogram machines, defibrillators, and even implantable pacemakers were manufactured in Brazil which barely had an automobile industry, a gross national product about 15 times smaller than today and 40% of today’s population.
Several of Zerbini’s disciples have founded other heart surgery groups. Two of them, Dr. Adib Jatene and Dr. Domingos Braile, have become remarkable surgeons and professors and have also dedicated themselves to develop artificial organ technology and helped establish the first Brazilian industries in this area.
In May 1968, Zerbini performed the first heart transplant in South America and 17th in the world. This fact rendered him great local popularity (Fig. 2), fueled local pride, and was promptly seized by political leaders.
Figure 2
The patient survived for 28 days succumbing to rejection. In September of this same year, a second transplant was performed and an improved pharmacological approach warranted this patient a 14-month survival.
Zerbini used his prestige to obtain government funds to build the Heart Institute at the University of São Paulo Hospital, with 400 beds exclusively dedicated to cardiology, 18 surgery rooms, laboratories, and classrooms. Within the institute, important teaching activities and artificial organ research and development were carried out.
As a result of his widespread influence, 140 heart surgery centers function in Brazil, currently performing about 40 000 procedures a year. Hundreds of surgeons mainly from Latin America turned to São Paulo as a source of training (Fig. 3).
Figure 3
Figure 4
Those were times when low socioeconomic conditions prevailed in Brazil, and rheumatic valve disease was frequent in youngsters, making prosthetic valves a great need. In 1960, Albert Starr had performed the first successful ball valve prosthesis replacement in the mitral position. In 1964, fabrication of these valves began in Brazil through the initiative of talented Dr. Adib Jatene. By mid-1965, 300 Brazilians were already living with implanted Brazilian-made heart valves. They were sold in Brazil for 30 dollars vs. 300 dollars in the USA. But mechanical valves were associated with persistent thromboembolic complications, and the problem of utilizing and controlling anticoagulation was unworkable for the financially deprived Brazilian patients. “We were facing around 30% of thromboembolic complications with these mechanical valves,” recalls Puig.
Puig knew that in the search for an ideal substitute to replace diseased human valves, fascia lata had been employed. Reports using this tissue in the aortic position appeared in the literature 1. They were also implanted in the mitral and tricuspid positions. Puig wondered whether treated dura mater tissue like the one used previously for hernia repair would make a suitable material for a heart valve.
Zerbini gave him the “green light” for the idea. Recruiting his colleague Dr. Geraldo Verginelli as a coworker, they proceeded by sewing a handmade dura mater bioprosthesis supported by a metallic stent (Fig. 5). The resulting hydrodynamic characteristics were obtained using the equipment already present in the hospital for testing mechanical valves. Satisfied with the bench results, finally, in January 1971, Puig and Verginelli made their first clinical implant.
Figure 5
The results obtained in the first cases were satisfactory and thromboembolic problems practically vanished.
Stimulated by good results, dura mater harvest was refined, and antibiotics plus fungicides were added to the preserving glycerol solutions.
In 1977, Puig and his teammates published the results of the first 4 years experience involving 849 homologous dura mater valves implanted in 751 patients. The results thus obtained were satisfactory from the clinical and hemodynamic points of view 2.
Puig’s innovation did not go unnoticed in the international setting. In London’s National Heart Hospital, it was used in clinical setting 3. In Cleveland, it was found that dura mater valves were more durable than the glutaraldehyde-treated bovine valves for employment in ventricular assist devices (VADs) 4. At the Medical College of Ohio, St. Vincent Hospital, wide-ranging anatomic and pathological studies were undertaken 5.
In the early 1980s, the use of the dura mater bioprosthesis was discontinued in Brazil, regardless of its low calcification and good actuarial results. The heterologous porcine valve and pericardial bioprosthesis, prepared with glutaraldehyde, became the first choice for use in heart valve replacement due to the higher availability of these biological tissues, which allowed superior choice and quality control. Also, as the years elapsed, ethical guidelines for the harvest of human tissue became progressively stricter and difficult to observe. Although the rates of dura mater valve infection were within satisfactory limits, theoretical doubts regarding the sterility of glycerol treatment were frequently reminded.
When use of dura mater valves was discontinued, 3000 patients had gotten this implant, and results were very good when compared to other available valves 6.
Puig’s pioneering effort provided the practical means to sustain patients’ needs for many years. Brazil recognized Puig and his colleagues’ significance by issuing a postage stamp depicting a dura mater valve as one of Brazil’s more beneficial inventions (Fig. 6).
Figure 6
Currently, Puig still practices surgery in the academic setting and in the meantime has created other important innovations in cardiac surgery 7.
Biosketches
Adolfo A. Leirner was born in São Paulo, Brazil in 1936. He received his E.E. degree in 1958 from the Instituto Tecnológico da Aeronáutica in S. José dos Campos, Brazil. He received his MD, PhD, and Professorship degrees from the University of São Paulo’s Medical School. From 1986 to 2010, he was chairman of its Heart Institute Center for Biomedical Technology. Professor Leirner, who pioneered the design, testing, and manufacturing of Brazilian-made EKG machines, defibrillators, pacemakers and VADs, is coeditor of Artificial Organs and served for many years as board member for the International Society for Artificial Organs (now, the International Federation for Artificial Organs).
Luiz Boro Puig was born in Barretos, state of São Paulo, Brazil. He graduated from the University of São Paulo’s Medical School. He began working as assistant in cardiac surgery to Professor E.J. Zerbini in 1967. He earned his PhD in 1972 and his Professorship in 1976. In 1971, he conceived the dura mater heart valve prosthesis at the Heart Institute, University of São Paulo. Dr. Puig also contributed with many works related to cardiac revascularization techniques.