ASAIO GOLD

The 25 Landmark ‘Milestone’ Papers Published by ASAIO

1955-2003

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Artificial Lungs

1. Clowes GHA Jr, Hopkins AL, Kolobow T: Oxygen diffusion through plastic films. TASAIO 1:23-24, 1955.

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 (landmark paper #18).

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 which became known as tumor necrosis factor. --- Robert Bartlett, MD

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2. Kolobow T and Bowman RL, "Construction and evaluation of an alveolar membrane heart lung," Trans Am Soc Artif Intern Organs 9:238-245, 1963.

Commentary: Ted Kolobow presented this paper at the 9th 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. ( ASAIO Landmark paper #17)  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 coli"). Secondary flows in the blood path were generated by intermittent suction on the exhaust gas, which also solved the problem of pin holes 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, 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 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 Bartlett, M.D.

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3. Bartlett RH, Gazzaniga AB, Jeffries MR, Huxtable RF, Haiduc NJ and Fong SW, "Extracorporeal membrane oxygenations (ECMO) cardiopulmonary support in Trans Am Soc Artif Intern Organs 22:80-93, 1976.

Commentary: In the 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, MD

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