About Us

ASAIO History Group

A collaborative historical project of ASAIO, the National Library of Medicine at the National Institutes of Health, and the Smithsonian Institution’s National Museum of American History, The ASAIO History Group was launched in 2000 to document and preserve the rich history of artificial organ development, from discovery to clinical use.

 

An important and timely undertaking, this medical history project aims to preserve and present the people, ideas and devices instrumental in the innovation and realization of artificial organs.

ASAIO History Group Mission:

To recognize individual and corporate contributions to artificial organ history;
To identify the pioneers and their contributions to improved quality and length of life;
To document the experiences of scientists, engineers, clinicians and patients developing and using artificial organs;
To link these past accomplishments to present and future developments;
To encourage education, scholarship, and research on artificial organ history.

History Group  Leaders

President Windmill CV Systems Inc.

Mark Kurusz, BS
President
Windmill CV Systems Inc.

Peter Wearden

Peter Wearden, MD, PhD Assistant Director & Chair Cardiac Center Nemours Children’s Hosp, Orlando

George Pantalos, PhD Professor of CV & Thoracic Surgery - University of Louisville

George Pantalos, PhD
Professor of CV & Thoracic Surgery – University of Louisville

 

William Weiss, PhD Professor Surgery & Bioengineering  Penn State College of Med

William Weiss, PhD Professor Surgery & Bioengineering  Penn State College of Med

Gershon Rosenburg, PhD

Gerson Rosenberg, PhD
Professor Surgery & Bioengineering
Penn State College of Medicine

Steven Phillips, MD Assistant Director National Library of Medicine

Steven Phillips, MD
Research Scientist
NLM/NIH

 

President LVAD Technology

Jean Kantrowitz, MPH
President LVAD Technology

Project Bionics Bibliography

The 25 Landmark Papers Published by ASAIO 1955-2003

These papers were selected by the membership of ASAIO. Commentaries by Project Bionics introduce the papers.

Artificial Kidney (Hemodialysis)

1. Kolff WJ: The artificial kidney—past, present and future. Tr Am Soc Artif Intern Organ 1955;1:1-7.

Commentary: This article is the first paper printed on pages 1 to 7 of volume 1 in Transactions ASAIO by Willem J. Kolff. This transaction was typed by June Salisbury, wife of Dr. Peter Salisbury, the founder of ASAIO and the third president of ASAIO (1957-1958). The congress was held in Hotel Chelsea in Atlantic City on June 4, 1955 by 47 founding members. Most of them were interested in developing the artificial kidney and the heart-lung bypass machine.

Dr. Kolff was the founding president of ASAIO during 1955-1956. Thus, this article should be considered as the first presidential address of ASAIO. As everybody is well aware, Dr. Kolff is credited with the first clinical use of the artificial kidney in 1943 as well as currently promoting the development of the wearable artificial kidney.  His achievements also include development of an artificial heart and cardiac assist devices. He also has interest and experience in organ preservation for transplantation, blood oxygenators, biomaterials, and artificial eyes and limbs. Dr. Kolff, while truly the original pioneer of artificial organs, remains in the forefront of modern artificial organ development during the last 60 years.

Willem Kolff was born in The Netherlands and received his M.D. in Leiden in 1938 and a Ph.D. degree based upon “Die Kunstliche Niere” from the University of Groningen in Holland in 1946. From 1950 to 1967 he was affiliated with the Cleveland Clinic Foundation, ultimately as scientific director of the Artificial Organs Programs. Since 1967 he has been the distinguished professor of surgery and medicine and at the School of Medicine of the University of Utah until he became 90 years old. In 1986, he received the Japan International award. In 2002, he received the Lasker for Clinical Medical Research Award because he made the first kidney dialysis machine in 1943.

This paper was voted as a top ASAIO publication because after 50 years, approximately one million patients are being kept alive with the technologies developed by Dr. Kolff.—Yukihiko Nosé, M.D., Ph.D.

 

Three articles that forever changed dialysis– one million patients later. 

C.M. Kjellstrand, M.D., Ph.D., F.A.C.P., F.R.C.P.(C); C.R. Blagg, M.D., F.R.C.P.; T.S. Ing, M.D., F.A.C.P., F.R.C.P.(C, UK)

Commentary:  It is rare, for a single individual and group, to make as many contributions to medicine and mankind, as came out of Dr. Scribner and his team in Seattle in the 1960s and 1970s. Yet, all three articles, deemed the most important in dialysis by the ASAIO membership, came from that team in the early 1960s. Solutions to the problems of providing long-term dialysis poured out of the University of Washington, and Seattle became the Mecca for all of us who wanted to learn the technique and study the early experience and problems of long-term dialysis.

The development of dialysis for short-term treatment of life-threatening acute uremia took over 30 years. It started in 1912 at the Johns Hopkins University with dialysis first of rabbits, then of dogs, and in 1915 an exchange of 400-ml blood in a human. The term “artificial kidney” was coined in an article describing the Johns Hopkins vividiffusion apparatus that was published in the London Times in 1913. Haas did continuous dialysis of five patients in the mid-1920s. The first practical technical solutions came in the mid-1940s almost simultaneous by Kolff in the Netherlands, Alwall in Sweden, and Murray in Canada.

Artificial internal organs are the practical end products of curiosity, hypothesis and laboratory experiments to verify or reject the hypothesis. Some 230 years ago, Hilaire-Marin Rouelle’s curiosity of what is in urine led to boiling it dry and finding the white residue, which he named urea. Fifty years later in Germany, Friederich Wöhler, who had been a pupil of the Swedish chemist Berzelius who described the periodic system, synthesized and determined the size of the urea molecule. Half a decade later, Thomas Graham the father of colloid chemistry, separated molecules by dialysis in his laboratory. This was at about the same time that Claude Bernard hypothesized that maintaining the internal milieu was the true function of the kidneys. Curiosity, hypothesis, and laboratory experimentation laid the foundation. Knowledge knew no geographical boundaries in those days before “intellectual and—grotesquely—biological property.”

The practicalities of blood-thinning—leeches and heparin—and durable and blood-friendly membranes followed and set the stage for the apparatus developed by Abel, Rowntree and Turner at Johns Hopkins University. They prophesized that a solution to uremia would soon come but two world wars delayed this for more than three decades. Dialysis treatment for acute renal failure took off after World War II.

One dread we all had in those days was to start a patient on dialysis and then find that renal function did not return. There are only so many blood vessels and sites that can be cut down for connection to an artificial kidney and sooner or later these ran out. Several physicians sought for the Holy Grail of endless connections of man to machine. Alwall tried using glass-cannulas in an artery and a vein and shunted with a piece of rubber tubing between dialyses but this did not work. The material was wrong and the shunt stayed open for only a couple of days even with the help of dangerous amounts of heparin. Parsons tried using available plastic tubing in the late-1950s but the result was the same.

When Scribner was faced with the problem in 1960, Teflon tubing had just become available. It worked. Literally overnight the solution was there and soon the number of patients began to grow beyond everybody’s predictions. Today more than a million people are alive and on chronic dialysis, thanks to the observation, perseverance, intelligence, clinical research, and generosity of Dr. Scribner and his team. The 1960s were the glory days of nephrology before the era of destructive patent fights and dialysis for profit. Not a penny for personal use came from what was the most important discovery in modern nephrology!

The three papers selected below are among the most important contributions to dialysis in the Transactions ASAIO and illustrate the quick transition from discovery through experiment to practical application.

 

2. Quinton W, Dillard D, Scribner BH: Cannulation of blood vessels for prolonged hemodialysis. Tr Am Soc Artif Intern Organ 1960;6:104-113. and Scribner BH, Buri R, Caner JEZ, Hergstrom R,  Burnell JM: The treatment of chronic uremia by means of intermittent  hemodialysis: A prelimninary report. Tr Am Soc Artif Intern Organ 1960;6:114-122.

Commentary: All is there—the dimensions; the detailed instructions for using the heating contraption for bending Teflon tubing and extruding the vessel tip that caused burns on so many nephrologists’ pinkies; the care needed to cut the tip just right to fit it to the size of the blood vessel while avoiding any frayed edges and the little pliers that allowed one to do so; the arm plate; the complicated “Swagelok” connectors that were plumbing supplies; a careful description of the surgical technique; and the histological proof that the cannula did not set up any destructive tissue reactions. It is all there in crystal clear terse prose. The paper is only six pages long, double-spaced and in large print, with three pages of illustrations. This was the solution to the problem of repeated dialyzer connections that previously had frustrated everyone.

What is less well known is that this paper was never presented at the ASAIO annual meeting. The shunt was first used on March 9th of 1960, but the program for the ASAIO meeting that April was already complete. Scribner took the patient, Clyde Shields, Clyde’s wife, and Wayne Quinton, the engineer, to the meeting in Atlantic City. Clyde was shown to a small group that included Pim Kolff, John Merrill, and George Schreiner at a breakfast meeting, and that evening in his hotel room Quinton demonstrated how to fabricate the shunt. Schreiner, who was editor of the Transactions ASAIO, realized the importance of this development and allowed Scribner to write it up for publication in the 1960 Transactions.

Preceding the cannulation paper in the 1960 Transactions is a detailed description of the technique of prolonged continuous hemodialysis that was presented at the meeting. In 1959, Paul Teschan had reported the benefits of prophylactic intermittent hemodialysis in the treatment of acute renal failure. Scribner thought that an alternative approach would be continuous hemodialysis for 24 hours at a time and developed a system to provide this. With development of the Teflon shunt this was used to treat the first patients with chronic renal failure.—C.M. Kjellstrand, M.D., Ph.D., F.A.C.P., F.R.C.P.(C); C.R. Blagg, M.D., F.R.C.P.; T.S. Ing, M.D.. F.A.C.P., F.R.C.P.(C, UK).

 

3. Scribner BH, Caner JEZ, Buri R, Quinton WE: The technique of continuous hemodialysis. Tr Am Soc Artif Intern Organ 1960;6:88-93.

Commentary: The team describes the technique in great detail, including the mathematical considerations of urea removal underlying the use of the huge 15 cubic foot home freezer tank, and the reasoning behind choosing a low resistance parallel-plate dialyzer so as to allow enough blood flow without the use of a blood pump. Dialyses were done with dialysate at 40 C as this cold temperature inhibited bacterial growth and also reduced clotting in the extracorporeal circuit. The report details how to connect the Teflon cannulas to the very long 20 feet of blood tubing that allowed the arterial line to pass through the dialysate tank to cool blood entering the dialyzer and let the venous line pass through a warming bath before returning to the patient.  It also allowed the patient to move around during the very long dialysis runs. Some acute patients were hooked up to the system for up to 14 days! The paper includes a brief description of the 10 patients with acute renal failure and eight with chronic renal failure that provided the clinical basis for the metabolic calculations. Twenty grams of nitrogen, corresponding to a combined catabolic/dietary intake load of 120 grams of protein, was removed daily.

These two papers were the shots heard around the world of physicians dealing with uremia that was the start of the revolution against the early death of end-stage renal disease. The Seattle team continued their research at a breath-taking speed. Articles related to the medical problems of anemia, bone disease, hypertension, and other associated serious medical problems also first originated from Seattle. In addition, other equally vexing problems not previously considered were dealt with head on. These included reports on the world’s first out-of-hospital community dialysis unit, experiences of taking care of a large number of patients, and the ethics of patient selection. Scribner’s presidential address to the ASAIO in 1964 on the latter subject is still worth rereading.

Thirteen years later, hearings in the U.S. Congress resulted in the incorporation of dialysis and kidney transplantation into Medicare. At that time there was no comprehension of the magnitude of the program that would result. The latest forecast from the U.S. Renal Data System suggests the need to provide care to 600,000 patients in the U.S.A., 0.2% of the entire U.S. population, by the end of the present decade! —C.M. Kjellstrand, M.D., Ph.D., F.A.C.P., F.R.C.P.(C); C.R. Blagg, M.D., F.R.C.P.; T.S. Ing, M.D., F.A.C.P., F.R.C.P.(C, UK).

 

4.  Eschbach JW, Jr., Wilson WE, Jr., Peoples RW, Wakefield AW, Babb AL, Scribner BH: Unattended overnight home hemodialysis. Tr Am Soc Artif Intern Organ 1966;12:346-362.

Commentary:  Dialysis was very expensive—and when this paper was published seven years before the Congress acted it was out of reach of almost anyone but the richest patient. The obvious solution was to send the patients home for dialysis. The Seattle team set out to solve all the problems that came with this. It soon became obvious that the long treatment times greatly interfered with the lives of patients and their families and the solution suggested by Stanley Shaldon was overnight dialysis.

The equipment used was the first single patient system using proportioning pumps to make dialysate. Three monitors were developed to solve the problem of patient safety in the home: a blood leak detector, a negative pressure monitor in the dialysate compartment, and an arterial blood pressure monitor in the extracorporeal circuit. The equipment, training, maintenance, and medical supervision are described. It is hard today not to laugh out loud or to develop acute depression on reading the cost analysis that showed the initial cost of equipment, home remodeling, and two months of training came to all of $12,800 and from then on the yearly cost was $4,150—physician payment and laboratory costs were each $200! The paper details the various medical, technical, and psychological problems of the first eight patients and the ways to deal with them. The patient who had been on the system the longest had 24 months of experience and total experience for the whole program was 94 patient months. The difficulties of performing remote monitoring—two of the patients were in California and one in Madras, India—and how this problem was solved by cooperation with local physicians are explained.

It would take another 30 years before this experience was reproduced in Toronto and further improved by dialyzing every night rather than three times weekly.

Many of the lessons taught by the Seattle team, especially the importance of long dialysis times to combat hypertension, fluid overload and cardiovascular disease, were forgotten as commercial priorities, supported by a wrong-headed emphasis solely on small molecule removal, led to cranking up of dialyzer urea clearance while shortening dialysis time. Much is now being relearned. Time on dialysis is in itself of great importance in the survival of dialysis patients. “There is nothing new under the sun, everything has been done before!”

One cannot help but marvel at the unprecedented and tantalizing accomplishments and feel one’s spirits buoyed, while reviewing the heydays and trailblazing of dialysis so exquisitely illustrated by these three landmark publications that began the effort to banish death from chronic renal failure from the list of hopelessly incurable diseases!—C.M. Kjellstrand, M.D., Ph.D., F.A.C.P., F.R.C.P.(C); C.R. Blagg, M.D., F.R.C.P.; T.S. Ing, M.D. F.A.C.P., F.R.C.P.(C, UK).

 

5. Henderson LW, Besarb A, Michaels A, Bluemle LW Jr: Blood purification by ultrafiltration and fluid replacement (diafiltration). Tr Am Soc Artif Intern Organ 1967;13:216-225.

Commentary: Medical therapy is an interdisciplinary field, and advances evolve at the interface of basic science, engineering, and medicine. Physicians and bioengineers make progress in disease therapy by borrowing technologies and applying them to solve certain problems. In this paper Henderson and others clearly describe the problem with use of diffusion for removal of uremic substances in hemodialysis devices. Especially for larger solutes, diffusion is a significant limitation to their removal. Up to the time of this publication, ultrafiltration was “a familiar process” for removal of fluid and water during dialysis. These authors for the first time explained the potential for hemofiltration membranes to remove large toxins at rates equal to that of small toxins, up to the molecular weight cutoff of the membranes. Beyond merely providing a hypothesis, the authors outlined details on everything needed to make hemofiltration workable: the membranes (newly developed flat sheet Diaflo membranes of net neutral charge), the proposed chemical components of sterile replacement fluid (reconstitution fluid), and how to obtain any desired ultrafiltration rate from blood. In addition there is elegant testing to demonstrate a near zero reflection coefficient for uremic toxins and a high reflection coefficient for plasma proteins. A theoretical model is provided to predict required membrane surface area of a clinical hemofiltration device to give 300 ml/min ultrafiltrate. In spite of all of the elements described in this paper, hemofiltration wouldn’t be practical until the membranes were produced in hollow fiber rather than sheet form. Prophetically, Lipps and others first described “The Hollow Fiber Artificial Kidney” at this same ASAIO meeting and in this volume of ASAIO Transactions, page 200. —Stephen R. Ash, M.D., F.A.C.P.

 

6.  Menno, AD, Zizzi J, Hodson J, McMahon J: An evaluation of the radial arterio-venous fistula as a substitute for the Quinton shunt in chronic hemodialysis. Tr Am Soc Artif Intern Organ 1967;13:62-76.

Commentary:  When we look at medical practice in retrospect, commonplace things and practices that seem obvious now to us were almost never obvious at the time of invention. The arterio-venous fistula for chronic dialysis access is one example. In 1960, Quinton, Scribner and others first published on the “Silastic-Teflon bypass cannula” arteriovenous (AV) shunt, in ASAIO Transactions (see papers #3 above). This access was clearly an “engineer’s solution,” hydraulic and mechanical in design, a permanent transcutaneous device with separable parts. The AV shunt was somewhat cumbersome and occasionally risky though when placed properly quite successful, and the device established the first practical blood access for chronic hemodialysis. Nothing could have been more contrary to this device, or a more purely  “biological” approach, than the arteriovenous fistula. Instead of creating a permanent transcutaneous tract, the AV fistula changed native anatomy, allowing enlarged veins to be intermittently and easily cannulated with needles that were placed for dialysis then removed. Brescia, Cimino and Appel (all nephrologists, by the way) first published on this type of access in TheNew England Journal of Medicine late in 1966. However, the earliest informal presentation in the U.S. was probably that of Cimino, in a short discussion requested by Dr. Galletti at the 1966 ASAIO meeting (Transactions ASAIO, vol 12, pg 227). Here he describes 14 months of experience in 10 dialysis patients with AV fistulae, which he refers to as “non prosthetic fistulae.” He briefly describes the method of creation of the radial artery/cephalic fistula, and then describes the proper position and direction of the needles to diminish admixture of outflow and treated blood (also providing a clear photograph). But, he raises several questions regarding this new idea: can it cause high output heart failure, do patients mind the needlesticks, do the veins hold up to repeated puncture, and are there complications?

By the next year’s ASAIO meeting, Menno, Zizzi, Hodson and McMahon from Deaconess in New York were ready to present a paper answering many of the basic questions regarding AV fistulas for use in dialysis, based on experience in 10 patients. Using well-done angiograms they showed that there were few changes in the vein wall after 9 months of use of a fistula for dialysis (152 punctures). Only one patient of 10 developed “arborized” veins. Cardiac output determinations by cardio-green dye dilution method showed an increase of resting cardiac output of only10-28%. Heart size increased in only three patients, and in these patients depended upon control of hypertension and salt balance. The patients’ acceptance of the fistula was very high, especially compared to the Quinton shunt, with patients stating “freedom from the encumbrance of the Teflon-Silastic cannulae, freedom to swim and bathe at will, and a release from a constant anxiety about thrombosis, infection, and disruption of the plastic shunts…” From this publication onward, the AV fistula was here to stay as the best possible dialysis access. Over the years however there has been a tendency in the U.S. to develop and use more mechanistic and artificial access approaches, including the arteriovenous PTFE graft and cuffed, tunneled central venous catheters. Recent educational programs by the renal Networks and CMS such as the “National Vascular Access Initiative” have been developed to re-educate nephrologists and surgeons about the intrinsic safety and longevity advantages of the AV fistula versus any other access. These programs should start by distributing this landmark and compelling paper from ASAIOTransactions, 1967. —Stephen R. Ash, M.D., F.A.C.P.

Commentary: Throughout the 1960s and 1970s surgical residents learned the tedious details of construction, management, declotting, and replacement of Quinton Scribner shunts. Although the external silicone rubber shunt made chronic intermittent hemodialysis possible, the hardware needed constant tending. This paper by Menno and others was one of the first to describe creation of a forearm arterial-venous fistula to provide access for intermittent chronic hemodialysis. As the AV fistula matured, the ready accessibility of the large, tough, pulsating veins on the surface of the forearm gradually made the external prosthetic shunt obsolete. When this paper was presented in 1967 the idea of such an invasive procedure simply to dialyze the few patients dependent on chronic hemodialysis seemed rather outrageous. Not even the most optimistic nephrologist anticipated the fact that hundreds of thousands of patients with chronic renal failure would be managed in this fashion decades later.—Robert H. Bartlett, M.D.

 

Cardiopulmonary Bypass for Cardiac Surgery

7. Gibbon JH Jr: Artificial heart-lung machines: chairman’s address,” Tr Am Soc Artif Intern Organ 1955;1:58-62.

Commentary: It was fitting that Dr. John Gibbon, Jr. was not only persuaded to become a member of the newly formed ASAIO but that he chair a session on heart-lung machines at the first meeting. Twelve papers, out of 28 total on the program that year, dealt with blood pumps and gas exchange. Dr. Gibbon took the moderator’s prerogative to add some perspective to the proceedings by reviewing his considerable personal experience leading up to the first successful clinical use of a heart-lung machine for closure of an atrial septal defect. The case had been performed just two years earlier, and he expressed justifiable pride in having accomplished this momentous feat by saying, “It is nice to have this successful operation on record.”

He also offered his assessment of the current state of the art with artificial hearts and lungs as compared to other methods used when performing open-heart surgery in the 1950s. He predicted that heart-lung machines would enable the new field of cardiac surgery to develop with less risk than using either hypothermia or cross-circulation. He talked about problems in obtaining accurate diagnoses and of poorly understood results of surgical correction of some congenital lesions. He alluded to patients of his who did not survive open-heart surgery after the one successful case, and even suggested that a heart-lung machine might not be necessary for closure of a simple atrial septal defect. Expanding on his review of the current status of the apparatus, he qualified it as being “…a perfectly adequate method of gas exchange without any danger of air embolism,” and went on to say that the problem of handling coronary venous return had been solved and that blood pH was automatically controlled.

He mentioned younger workers several times in his paper and said he felt like an old man (he was just 51-years-old). He believed the new investigators within ASAIO’s ranks would carry on with refinements in the technology and “make significant contributions to this field in the future.” In hindsight, his prediction was spectacularly prescient. —Mark Kurusz, C.C.P.

 

8. Clark LC Jr: Monitor and control of blood and tissue oxygenation. Tr Am Soc Artif Intern Organ 1956;2:41-45.

Commentary: Dr. Leland C. Clark, Jr. is the developer of the Clark oxygen electrode and is considered as the father of the biosensor concept. This development has served as the standard in the field. In this paper he describes improvements in the use of his electrode for the continuous monitoring of oxygen tension in blood in a bubble-defoaming device for blood oxygenation. The basic principle of his electrode employs the polarographic measurement of oxygen using a barrier (oxygen permeable membrane) that does not require tissue or blood contact with the electrode’s cathode or anode.

He pioneered work in the development of oxygenating systems in the early 1950s with Frank Gollan and Vishwa Gupta as well as chronic monitoring of oxygen in perfusion. In an 1962 address to the New York Academy of Sciences he described how to make electrochemical sensors (pH, polarographic, potentiometric, or conductometric) more intelligent by adding enzyme transducers as membrane enclosed sandwiches. He coined the term enzyme electrode. Clark’s ideas became a commercial reality with a successful re-launch of the Yellow Springs Instrument Company (Ohio) glucose analyzer based on amperometric detection of hydrogen peroxide. This was the first of many biosensor-based laboratory analyzers to be built by companies around the world. —Paul S. Malchesky, D.Eng.

Commentary:  Two issues were paramount for those performing extracorporeal circulation in the 1950s: first, the need for reliable monitors of adequacy of perfusion and, second, simplicity of device design. In this regard, the Clark electrode for measurement of oxygen tension in either flowing blood or organs fulfilled these two goals. Dr. Clark’s rationale for developing the small glass and polyethylene membrane probe was based on his belief that, “…the more information we can obtain concerning the physiological status of the patient or animal, the more intelligently the [heart-lung machine] can be designed and controlled.”

He discussed the optimum size of bubbles for oxygenation and carbon dioxide removal for a bubble or “dispersion”-type oxygenator, which he and colleagues, Frank Gollan and Vishwa Gupta, described in 1950. Helmsworth, Clark and others subsequently used it clinically in 1952 on a 45-year-old man with fibrotic lungs and cor pulmonale. The patient’s symptoms improved during the 75-minute period of partial respiratory support. One year later, the same group used the apparatus for cardiac surgery on a 4-year-old boy with a preoperative diagnosis of atrial septal defect. Despite large volumes of coronary venous blood that led to hemodynamic problems, the patient was weaned after 33 minutes of extracorporeal support. He awoke, was extubated and responded, but died 16 hours after surgery from renal failure and brain damage, which was attributed to prolonged hypotension during perfusion. The congenital lesion was also found at surgery to be a partial arteriovenous canal.

Despite these early disappointments, the heart-lung machine functioned “perfectly”, due in part to use of the Clark electrode. Today, inline sensors, several versions improved over that first described by Dr. Clark, are indispensable tools to monitor blood gases and safely manage perfusion. In the discussion following this paper, Dr. Clark noted that the response time for the probe and recorder to equilibrate was a matter of 3-4 seconds and that oxygen tension values were continuously displayed. Another discussant called the Clark electrode a “fundamental contribution” in studying organ physiology during acute or chronic experiments.—Mark Kurusz, C.C.P.

 

Cardiac Valves

9. Hufnagel C, Villegas A: Aortic valvular replacement. Tr Am Soc Artif Intern Organ 1958;4:235-239.

Commentary: The Hufnagel ball valve originated from an idea that was patented in 1858 by John Williams for a bottle stopper. Dr. Charles Hufnagel, professor of surgical research at the Georgetown University Medical Center, began experimenting with an aortic valve prosthesis in 1946.The Hufnagel valve was intended to be placed in the descending aorta and not in the subcoronary position. This valve was implanted clinically for the first time in the descending aorta in 1952. Among the first 10 patients there were four deaths, but considering that these patients were in the terminal stages of severe aortic incompetence, the results were favorable. Anticoagulants after surgery were not used, and it is interesting to note that there were no cases of valve malfunctioning or clotting. Though not very efficient in relieving aortic insufficiency, the Hufnagel ball valve demonstrated, for the very first time, that a prosthetic valve device could be successfully placed in the human circulatory system. The Hufnagel valve ushered half a century of design improvements in mechanical cardiac valves beginning with the ball-and-cage design first commercialized as the Starr-Edwards valve in 1961. —Steven J. Phillips, M.D.

 

Vascular Grafts

10. Edwards WS, Tapp JS: Two-and-a-half-years experience with nylon grafts. Tr Am Soc Artif Intern Organ 1957;3:760-772.  [confirm page nos.]

Commentary: This article details the authors’ clinical experience with vascular prosthesis made of nylon. The authors, from Birmingham, Alabama, working with the Chemstrand Corporation of Northern Alabama (a subsidiary of Monsanto) developed a tubular prosthesis for replacement or bypass of diseased arteries. In the process of manufacture, the prosthesis accidentally became crimped, and the authors, serendipitously, realized that this may prevent graft occlusion by kinking. This graft, along with others, was discussed at length at the 10th Annual Meeting of the Society for Vascular Surgery. In spite of early expectations, other properties of nylon proved to be undesirable for use in humans, and other materials gained rapid acceptance. Incidentally, the Chemstrand company is now known for the manufacture of artificial turf for athletic fields. Dr. Edwards moved to New Mexico where he enjoyed a full and productive career and has had heavy influence on the structure of the scientific program of the Rocky Mountain Vascular Surgical Society. —W. Gerald Rainer, M.D.

 

Cardiac Devices

11.  Cooley D, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milan RC: First human implantation of cardiac prosthesis for staged total replacement of the heart. Tr Am Soc Artif Intern Organ 1969;15:252-263. (Discussion following Kwan-Gett CS, Wu Y, Collan R, Jacobsen S, Kolff WJ: Total replacement artificial heart and driving system with inherent regulation of cardiac output. Tr Am Soc Artif Intern Organ 1969;15:245-251.)

Commentary: At the invitation of Dr. Willem Kolff, and a late addition to the original program, this paper by Dr. Denton A. Cooley reports on the historic first clinical application in 1969 of a total artificial heart (TAH). It describes the concept of two-staged cardiac transplantation (practiced widely as bridge-to-transplantation today) for the emergency setting of acute irreversible cardiac failure, precluding orderly donor organ procurement and elective transplantation.

The patient was a 47-year-old male with severe diffuse coronary disease, complete heart block, extensive left ventricular fibrosis and a 10-year history of myocardial infarctions, arrhythmias, and congestive failure. The patient was opposed to cardiac transplantation, the procedure of choice, and opted for myocardial excision with ventriculoplasty—a procedure he had seen reported on the news. A wide resection of nonfunctional myocardium was carried out, but inadequate cardiac function prevented weaning from cardiopulmonary bypass, thus necessitating mechanical circulatory support. The pneumatic TAH employed, developed by Dr Domingo Liotta with the Baylor-Rice team and tested in a series of seven short-term bovine experiments, was “covertly taken from the Baylor surgical laboratory to St. Luke’s Hospital” (as reported by Dr. Michael DeBakey). Implanted orthotopically, the Liotta TAH provided satisfactory circulatory support for 64 hours, although renal and respiratory function were marginal. Thirty-two hours following cardiac transplantation, the patient died of Pseudomonas pneumonia, likely related to the administration of azathioprine immunosuppression soon after TAH implant.

A second staged cardiac transplantation was carried out by Cooley some 12 years later, using the Akutsu III pneumatic TAH, but with a similar outcome. The first successful bridge-to-transplantation was not achieved until 1984 (Dr. Philip Oyer, Novacor LVAS), and the first successful TAH bridge was accomplished a year later (Dr. Jack Copeland, Jarvik 7 TAH).—Peer M. Portner Ph.D.

 

12. Joyce LD, DeVries WC, Hastings WL, Olsen DB, Jarvik RK, Kolff WJ: Response of the human body to the first permanent implant of the Jarvik-7 total artificial heart. Tr Am Soc Artif Intern Organ 1983;29:81-87.

Commentary: At the ASAIO meeting in 1982 Don Olsen chaired a panel conference describing the indications and plans for implantation of a total artificial heart (Tr Am Soc Artif Intern Organ, vol 28, pg 652). Later in 1982 the Utah team lead by surgeon William DeVries implanted a total artificial heart in patient Barney Clark. The case was reported in the lay press and at every scientific meeting. Barney Clark lived in the hospital with this total artificial heart for many months, finally succumbing to an embolic stroke. The first successful implantation of a total artificial heart was the subject of great excitement at the 1983 ASAIO meeting. This was the culmination of decades of research in dozens of laboratories, and the culmination of the NIH total artificial heart program. This landmark paper presented at the 1983 meeting, describes function of the artificial heart and physiologic responses to prolonged mechanical pumping. This paper is the most complete description of the course of Dr. Clark, and defines that normal organ function can be sustained indefinitely with a mechanical heart, and that thrombotic complications will be the subject of intense research while progress with implantable cardiac devices continues.—Robert H. Bartlett, M.D.

13.  Portner PM, Oyer PE, Jassawalla JS, Miller PJ, Chen H, LaForge DH, Skytte KW: An implantable permanent left ventricular assist system for man. Tr Am Soc Artif Intern Organ 1978;24:98-103.

Commentary:  Dr. Peer M. Portner had been a principal investigator in the NHLBI permanently implantable LVAD development program since 1970 through Andros Inc., Berkeley, California and subsequently Novacor Medical Corporation and the Novacor Division of Baxter Healthcare, Oakland, California, while holding a faculty position in the Department of Cardiovascular Surgery at Stanford University School of Medicine. The first fully integrated system, his electromechanical LVAD is based upon a dual pusher plate sac-type pump with controlled deformation, activated by a unique spring-decoupled solenoid. Thus, this electromechanical LVAD has proven to be effective, safe, and durable.

This paper by Dr. Portner, chosen as one of the 25 key ASAIO publications, represents the first description of a permanently implantable electromechanical LVAD system in detail. This LVAD was first implanted in a 51-year-old patient in 1984, in the world’s first successful bridge-to-transplantation. To date, more than 1,500 such devices have been implanted in patients for durations up to more than six years.  This paper supports the idea that the permanently implantable LVAD is not a dream; it is a therapeutically effective substitute for the natural heart. Currently this LVAD, recognized as the Novacor LVAS, is manufactured by WorldHeart Corporation, Ottawa, Canada and Oakland, California. It is one of the most effective, safe, reliable, and dependable LVADs in the world. After this Novacor LVAS system was introduced clinically, many other permanently implantable LVADs were introduced, including the Thoratec-TCI LVAS, the DeBakey MicroMed LVAS, and many others. —Yukihiko Nosé, M.D., Ph.D.

 

14. Kantrowitz A, Tjonneland S, Krakauer J, Butner AN, Phillips SJ, Yahr WZ, Shapiro M, Freed PS, Jaron D, Sherman JS Jr: Clinical experience with cardiac assistance by means of intra-aortic phase-shift balloon pumping. Tr Am Soc Artif Int Organ 1968;14:344-348.

Commentary: I was very fortunate to train with Dr. Adrian Kantrowitz. Dr Kantrowitz pioneered the development and implantation of temporary and permanent heart pumps—devices that, to date, have saved many thousands of lives. Dr. Adrian Kantrowitz also co-invented a plastic heart valve (1954), a heart-lung machine (1958), an internal pacemaker (1961), and an auxiliary left ventricle (1964). In 1966, Dr. Kantrowitz performed the first implantation of a partial mechanical heart on a human. On December 6, 1967, he performed the first heart transplant on an infant and the first in the United States. The initial clinical use of the intra-aortic balloon pump (IABP) for the treatment of cardiogenic shock was the culmination of years of research by Dr. Kantrowitz and his team. As I remember, one afternoon in 1967, Dr. Kantrowitz called me and said, “Steve, we’re ready to implant the balloon pump in a patient.” As a first year surgery resident, I was responsible for covering the emergency room at night. The break room next to the ER hosted a 24/7-poker game. That evening I stopped to check the ER and sat in for a few hands of poker. The room was filled with cigarette smoke, empty pizza boxes, and people playing poker. Sitting next to me was Dr. Menachem Shapiro, the Chief Medical Resident. I explained the function of the IABP to him and said, “Menachem, if you have a patient with cardiogenic shock, give me a call, and we will implant the IABP”. At 4 a.m. my phone rang and it was Menachem. He said. “Steve, we have a 48-year-old woman who is dying in cardiogenic shock. We have run out of medical treatment options. Come on over with your pump”. I mobilized the team and we met at the patient’s bedside. As it was 5 a.m., I did not want to awaken Dr. Kantrowitz, nor did Dr. Shapiro want to awaken his Chief. Drs. Tjonneland, Butner, and I inserted the first IABP. It functioned quite well, especially after Dr. Jordan Haller inserted a transvenous pacemaker to relieve the patient’s heart block. This first patient survived. At 7 a.m. we called our respective chiefs who hurried to the patient’s bedside. From its initial clinical use, over 37 years ago, to its current extensive use of over 100,000 times annually in the US alone, the intra-aortic balloon pump, developed and pioneered by Dr. Adrian Kantrowitz, remains the first choice intervention for mechanical circulatory assistance. A permanent balloon pump (the experimental patch booster) was commercialized as the CardioVad System and successfully implanted in a number of patients. The initial clinical implantations of the IABP, and its more permanent CardioVad spin-off demonstrated that LVADs can be successfully used for cardiac support. —Steven J. Phillips, M.D.

 

Pacemakers and Defibrillators

15.  Chardack WM, Gage AA, Greatbatch W: Experimental observations and clinical experiences with the correction of complete heart block by an implantable self-contained pacemaker. Tr Am Soc Artif Intern Organ 1961;7:286-295.

Commentary: This is a wonderful article classically describing early experience with an implantable pacemaker. With the state of the art in electrophysiology as it is today, it is difficult to conceive of the structure and function of the first pacemakers—huge in size because of the large mercury batteries; heavy (one-half pound); fixed rate (some rate and amplitude adjustability could be applied via a transcutaneous Keith, 3-sided needle); implanted via thoracotomy (induction of anesthesia not infrequently accompanied by cardiac arrest). Nonetheless, these same scientists went on to develop more efficient sources of energy, such as lithium in various combinations. Much credit goes to the space programs for the miniaturization of electronic components, which have been of value to the medical device industry. The accompanying illustrations with this article are magnificent in the portrayal of the early attempts at technology of this sort. —W. Gerald Rainer, M.D.

 

16.  Schuder JC, Stoeckle H, Gold JH, West JA, Keskar PY: Experimental ventricular defibrillation with an automatic and completely implanted system. Tr Am Soc Artif Intern Organ 1970;16:207-212.

Commentary:  A result of studies from the University of Missouri, this paper deals with the development of an implantable ventricular defibrillator, just as crude when compared with the transvenous systems of today as were the early pacemakers. The application of inefficient sensing and countershock delivery resulted in multiple instances of inadvertent and alarming shocks to the patients. Implantation was a major surgical adventure with abdominal wall placement of the power unit being required to accommodate the weight and bulk of the unit. Fortunately, technology has advanced rapidly in this field and many of the problems associated with earlier units have been overcome. —W. Gerald Rainer, M.D.

 

Artificial Lungs

17.  Clowes GHA Jr, Hopkins AL, Kolobow T: Oxygen diffusion through plastic films. Tr Am Soc Artif Intern Organ 1955;1:23-24.

Commentary:  This paper, presented at the first meeting of ASAIO, laid the groundwork for the entire field of artificial lungs using gas permeable membranes (membrane oxygenators). George Clowes was a forward-thinking, sometimes flamboyant, young surgeon who was on the faculty of Case-Western Reserve Medical School in Cleveland. Realizing the problems of blood damage associated with direct oxygen exposure in the early experimental oxygenators, Clowes investigated the diffusion of oxygen and carbon dioxide through thin films of plastic.  Kolff had observed that venous blood circulating through a cellulose membrane device became oxygenated indicating that gas transfer through solid membranes was possible. Clowes and his collaborators, A. Hopkins (an engineer) and Ted Kolobow (a medical student) investigated gas transfer through films of the relatively new polymeric materials known as plastic: polyethylene, polyvinyl chloride, cellophane, and Mylar. They did not evaluate polysiloxane (silicone rubber) because the gas-permeable properties of that material had not been described. This paper describes the actual data regarding gas transfer, demonstrates that membrane lungs would be feasible (although with very high surface areas), and predicted the development of membrane gas exchange devices. Nearly a decade later Kolobow described a silicone rubber membrane lung which became the basis for all subsequent membrane oxygenators (See landmark paper #18 below).

George Clowes moved to Boston where he continued to work on artificial organs but also on the pathophysiology of shock and metabolism. He described a circulating factor in shock and trauma, which caused protein catabolism. He called this compound “cachexin” and characterized its chemical and physiologic properties.  This was the first demonstration of the cytokine that became known as tumor necrosis factor. —Robert H. Bartlett, M.D.

 

18.  Kolobow T and Bowman RL: Construction and evaluation of an alveolar membrane heart lung. Tr Am Soc Artif Intern Organ 1963;9:238-245.

Commentary: Ted Kolobow presented this paper at the 9th ASAIO meeting in 1963. As a medical student in Cleveland in 1955, he had participated in George Clowes’ classic work on gas transfer through plastic membranes. (See landmark paper #17 above) By the time of this presentation he was working with legendary Robert Bowman at the Laboratory of Technical Devices in the National Heart Institute at NIH. After Dr Bowman retired, Dr. Kolobw became director of the lab. This paper described the design construction and testing of a membrane oxygenator using reinforced flat sheets of silicone polymer fabricated into a long envelope with a fiberglass screen spacer, all wrapped around a central core (a “spiral coil”). Secondary flows in the blood path were generated by intermittent suction on the exhaust gas, which also solved the problem of pinholes and gas leaks (a common problem at the time). The device also included an integral pump, which was not used in the final commercial design. This membrane oxygenator was manufactured by Sci Med of Minneapolis and later by Avecor, and then Medtronic. It has been the only solid silicone membrane oxygenator consistently available to investigators and clinicians for over 30 years. The Kolobow oxygenator has been used for almost all of the 30,000 patients treated with extracorporeal membrane oxygenation (ECMO) for heart or lung failure. The basic design is unchanged from the original description in this paper. The reliable safe blood interface effects were dramatically better than the gas interface oxygenators of the early heart-lung machines, leading to universal use of membrane oxygenators today. Dr. Kolobow has made many major contributions in artificial organs and in the pathophysiology of acute lung injury. This paper is among them. —Robert H. Bartlett, M.D.

 

19. Bartlett RH, Gazzaniga AB, Jeffries MR, Huxtable RF, Haiduc NJ, Fong SW: Extracorporeal membrane oxygenation (ECMO) cardiopulmonary support. Tr Am Soc Artif Intern Organ 1976;22:80-93.

Commentary: Inthe mid-1970s, many had attempted (with very limited success) to apply the infancy heart-lung machine to treat critical illnesses, such as acute pulmonary embolism, severe pneumonia, near-drowning, and traumatic pulmonary contusion. This landmark article by the creative mind of Robert H. Bartlett and coworkers details the first successful patient experience with extracorporeal membrane oxygenation (ECMO) in neonates. Following years of development in the large animal laboratory, this experience reports the vascular access techniques, circuit design, blood flow rates, continuous heparin infusion and anticoagulation monitoring, and team training necessary for successful ECMO. The entire initial patient cohort is reported in sufficient detail to allow critical assessment of those management techniques and choices, which appeared to be successful. The major innovation was to miniaturize a conventional cardiopulmonary bypass circuit, previously limited to open-heart surgery, mating major vascular cannulation, a closed circuit servo-regulated roller pump, and a spiral wound silicone membrane lung to the neonatal population for short-term (days) total cardiopulmonary support to allow reversal of acute cardiac or respiratory failure.

From this report, the fields of neonatology, pediatric surgery, and pediatric cardiac surgery were revolutionized to allow direct treatment of severe respiratory failure addressing such high-risk illnesses in neonates as meconium aspiration, neonatal sepsis, primary pulmonary hypertension, and congenital diaphragmatic hernia. Thirty years later, there are now over 120 recognized ECMO centers worldwide with over 25,000 patient experiences. ECMO is now considered standard of care for acute, severe, reversible cardiac or respiratory failure in neonates with approximately a 90% survival in patients thought to have only a 10% survival with continued maximum medical management. ECMO has more recently been successfully applied to selected patients in the pediatric and adult populations. ECMO also has inspired a new mindset in the management of mechanical ventilation such that low pressure, low volume “gentle” ventilation is the hallmark of lung rest and recovery.

The development of ECMO is an outstanding example of bench-to-bedside development of biomedical technology. Bartlett’s group spent several years addressing each of the management and technical problems in the large animal laboratory before applying the technique in humans. Over a productive 40-year career, Dr. Bartlett not only developed many innovations in artificial organ technology but also schooled a generation of critical care physicians and artificial organ enthusiasts who continue to explore the use of extracorporeal technology for respiratory, cardiac, hepatic, and renal failure.—J.B. Zwischenberger, M.D.

 

Artificial Liver and Apheresis

20.  Nosé Y, Mikami J, Kasai Y, Sasaki E, Agishi T, Danjo Y: An experimental artificial liver utilizing extracorporeal metabolism with sliced or granulated canine liver. Tr Am Soc Artif Intern Organ 1963;9:358-362.

Commentary: There are some clinical problems that are so daunting that simple approaches are unlikely to work, but nonetheless these are tried anyway. Acute liver failure was treated by hemodialysis as early as 1956 but results indicated no positive effects and the need for a more chemically selective approach was apparent (See Tr Am Soc Artif Intern Organ, vol 1, 1955). In this paper, Nosé and coworkers describe an elegantly simple approach to providing liver function through an extracorporeal blood treatment device. The basic idea was to use cellophane membranes to separate blood from a 10 liter tank of “metabolic fluid” containing enzymes, vitamins, amino acids, and importantly, metabolically active pieces of liver from a dog. In vitro tests demonstrated anaerobic and aerobic metabolism of liver was maintained in slices, homogenate, freeze-dried slices, and freeze-dried granules (freeze dried tissues allowed practical assembly of a device in the clinical area). The beauty of this approach is that while the metabolic products from the blood and liver pieces can transfer back and forth across the membranes, while proteins, enzymes, and immunologically active components stay only on the dialysate side. Typical of the determination of Dr. Nosé and coworkers, this first publication also included animal testing of the device. The survival extension after Eck-Fistula by their device rivals that obtained today with much more sophisticated bioartificial liver devices using cultured hepatocytes. Dr. Nosé also presented testing of the device in four patients with liver failure, and outcome of these patients was generally positive. After a huge effort in artificial liver support devices of the last 10 years, we are at a point of having proven benefit by treatment with bioartificial and artificial (sorbent) devices. However, papers like this make me wonder, did we make it all too complicated?—Stephen R. Ash, M.D., F.A.C.P.

 

Artificial Endocrine Organs

21.  Rohde TD, Blackshear PJ, Varco RL, Buchwald H: Protracted parenteral drug infusion in ambulatory subjects using an implantable infusion pump. Tr Am Soc Artif Intern Organ 1977;23:13-16.

Commentary:  This group, from the University of Minnesota and Massachusetts General Hospital, made the first clinical report of the use of an implanted drug delivery system at the 1977 ASAIO meeting in Montreal. It detailed the use of the device to deliver continuous heparin at a predetermined dose to 11 patients with recurrent thromboembolic problems for periods up to one year, and the technique allowed the patients to be managed in an outpatient setting. Their success occurred seven years after the initial experimental paper. This group went on to expand the use of the device to insulin infusion for diabetics and chemotherapy infusion for malignancies. —Leonard Golding, M.D.

Commentary:  This landmark paper presented in 1977 describes a remarkable pump designed by Henry Buchwald and Perry Blackshear, which became the prototype pump mechanism for continuous infusion of hormones, medications, and chemotherapeutic drugs for the next several decades.  Although the continuous infusion of insulin is and was a perfect way to control the swings in blood sugar associated with diabetes, the patient had to maintain quite a stable carbohydrate intake in order to avoid hypoglycemia, so this method of management of severe diabetes did not develop into a standard treatment because of the problems of sensing blood glucose and servo-regulating the pump infusion rate based on measured glucose. However, the concept of a continuous infusion pump powered by compression of a gas to a liquid below a flexible diaphragm is a superb example of bioengineering. —Robert H. Bartlett, M.D.

 

Biomaterials and Thrombosis

22. Gott VL, Whiffen JD, Koepke DE, Daggett RL, Boake WC, Young WP. Techniques of applying a graphite-benzalkonium-heparin coating to various plastics and metals. Tr Am Soc Artif Intern Organ 1964;10:213-217.

Commentary:  Pyrolytic carbon, the premier material for artificial heart valves was discovered in 1966 at General Atomics by Dr. Jack Bokros and by Dr. Vincent Gott, then at the University of Wisconsin. Dr. Bokros was using pyrolytic carbon to coat nuclear fuel particles for gas-cooled nuclear power reactors. In 1966, Bokros read an article by Dr. Vincent Gott, who had been testing carbon-based paint as a blood compatible coating for artificial heart components. Bokros contacted Gott who initiated the collaboration that resulted in creating medical grade pyrolytic carbon. Gott was searching for a material to use in artificial heart valves that demonstrated low thrombogenicity and mechanical durability. The initial material used to coat nuclear fuel particles had the needed blood compatibility, but not the durability. General Atomics initiated a development project headed by Dr. Bokros to add the needed durability to the material. This endeavor was successful and the biomedical grade of pyrolytic carbon, known as Pyrolite, was rapidly incorporated into heart valve designs. Nearly 40 years later, pyrolytic carbon remains the most widely used material for mechanical heart valves. It has been used in more than 4 million implants in more than 25 different valve designs for a clinical experience on the order of 18 million patient-years. No other material used for long-term blood contacting implants can boast of such a successful clinical experience.—Steven J. Phillips, M.D.

Artificial Cells

 

23.  Chang TM: Semi-permeable aqueous micro capsules (artificial cells) with emphasis on experience in extracorporeal systems. Tr Am Soc Artif Intern Organ 1966;12:13-19.

Commentary:  Dr. Thomas Ming Swi Chang is the originator of “artificial cells.” In this paper he discusses studies on the use of an extracorporeal shunt containing microcapsules with the enzyme urease to breakdown urea to form ammonia for the application in the treatment of renal failure. He also discusses approaches for microencapsulation of detoxifying agents as resins and charcoals to improve biocompatibility in blood contacting applications and for microcapsules containing red cell hemolysates such as artificial red cells. This paper builds on his pioneering work from just years earlier.

Dr. Chang built his career and laboratory focused on the area of microencapsulation and “cells” for medical applications such as related to the artificial kidney, artificial liver, detoxification, enzyme therapy, etc. since his Ph.D. work on “Semipermeable Aqueous Microcapsules.” In addition to this focus he is also recognized for his work in the artificial blood field on hemoglobin type products.—Paul S. Malchesky, D.Eng.

 

Plasmapheresis

24. Malchesky PS, Asanuma Y, Smith JW, Kayashima K, Zawicki I, Werynski A, Blumenstein M, and Nosé Y: Macromolecule removal from blood. Tr Am Soc Artif Intern Organ1981;27:439-444.

Commentary:  One of Woody Allen’s best lines in a movie was, “Ninety percent of success is just showing up.” In the field of medical therapy, ninety percent of progress is in the recognition of the problem with current therapies and in posing a logical and hypothetical solution. This paper by Malchesky, Nosé starts on a philosophical note, recognizing the ancient logic that most diseases are related to “humoral imbalance.” Then it clearly and succinctly lists the immunological and metabolic diseases for which this macromolecular or protein-bound toxins appear to be the cause, toxins that can be removed only by pheresis and plasma exchange. It then recognizes the various “disincentives” of plasma exchange, problems that are still faced today: loss of plasma solutes, requirement for replacement plasma products, risk of contamination, and potential loss of essential plasma constituents.

Malchesky and coworkers then describe two elegant solutions to this problem, both allowing selective removal of the maligned toxin or globulin and return of the plasma to the patient, mostly cleared of the toxin. First is sorbent column regeneration of the plasma. The authors review efficacy of removal of bilirubin and bile acids from plasma by sorbent columns such as anion exchange (see also three excellent papers in this same ASAIO Transactions on this topic by: Asanuma, Nosé and coworkers; Idezuki, Tanzawa and coworkers; Sideman, Brandeis and coworkers). This concept of plasmafiltration and sorbent regeneration of plasma is now time-proven, being pursued, optimized and proven today. Note the Prometheus machine (Falkenhagen), FPSA (Ronco), the general use of staph protein A and antiglobulin antibody columns in immunopheresis, the protein-toxin removing MARS device (Stange and Mitzer) and our own PF device. Good ideas stay; bad ideas just reappear now and then.

The second and even more novel approach for regenerating plasma is “cold filtration” of plasma and removal of cryoprecipitated (or gelled) globulins. There were only two prior publications on this concept, both from Malchesky and Nosé’s research group. In this paper the exact design of the cold filtration plasma regenerating apparatus is described, including the cooling circuit and the optimal membranes for removing the precipitated globulins. Clinching the argument for safety and efficacy, the authors describe clinical application of cryopheresis in patients with rheumatoid arthritis for up to one year with good success. This publication established the basic concept and value of pheresis with plasma regeneration. —Stephen R. Ash, M.D., F.A.C.P.

Neuroprosthesis

25.  Dobelle WH, Mladejovsky MG: The directions for future research on sensory prostheses. Tr Am Soc Artif Intern Organ 1974;20:425-429.

Commentary:  During ASAIO’s 50-year history, many neuroprostheses were introduced. Among them were cardiac pacemakers, phrenic nerve stimulators, intestinal stimulators, and bladder stimulators. However, attempts to develop sensory prostheses for the blind and deaf awaited the efforts of the University of Utah group headed by Dr. Willem J. Kolff. Even though Dr. Kolff could be credited with this field of technology, it was possible only after Dr. William H. Dobelle became involved in this field of artificial organs.

This particular paper was selected as one of the 25 most important papers during the last 50 years of ASAIO history because Dr. Dobelle’s objectives, approaches, and possible outcomes of artificial eye and ear were described 30 years ago and predicted today’s prostheses. This special address at the 20th anniversary of ASAIO introduced Dr. Dobelle’s idea of possible brain stimulation to help blind patients see and deaf patients hear. Since that time, this once thought impossible dream became reality. They are now clinically beneficial artificial organs.

All of us can learn from Dr. Dobelle insistence that only this type of artificial organ could be developed through human experiments and by implanting chronic electrodes in the brain to provide electrical stimulation. All of us including all government regulatory agents can learn from this fact. If these chronic human experiments had not been attempted before 1979, the current artificial eye and artificial ear prostheses would not exist today. One of the two patients implanted with an artificial eye in December 1978 is still alive and has improved during these 25 years. —Yukihiko Nosé, M.D., Ph.D.