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Artificial Organ History: A Selective Timeline

1885 --- M. von Frey and M. Gruber (Leipzig) build and use the first artificial heart-lung apparatus for organ perfusion studies. Their device relies on a thin film of blood and included heating and cooling chambers, manometers, and sampling outlets, which permits monitoring of temperature, pressure, and blood gases during perfusion.

1895 --- C. Jacobj (Germany) describes complex organ perfusion apparatus that relies on donor lungs for gas exchange.

1913 --- J.J. Abel, L.C. Rowntree and B.B. Turner at Johns Hopkins Hospital, Baltimore first describe in vivo hemodialysis of rabbits, dogs (and later a 400 ml blood exchange in a human) with an artificial kidney made of collodion and using hirudin anticoagulant.

1915 ---N. Richards and C. Drinker (Philadelphia) report use of a screen oxygenator for perfusion of isolated organs in which venous blood flows by gravity down a cloth in an oxygen-rich atmosphere.

1916 --- The anti-coagulant heparin is discovered by McLean and Howell.

1925 --- G. Haas (Germany) performs first clinical hemodialysis of 5 patients, using a modification of the Hopkins artificial kidney.

1927 --- H. Necheles in Beijing develops the first "sandwich" artificial kidney using a biological membrane consisting of calves' peritoneal membrane and dialyzes dogs.

1928 --- H.H. Dale and E.H.J. Schuster (Hampstead, UK) describe a double perfusion pump (for pulmonary and systemic circulations) relying on compressible diaphragms to circulate defibrinated blood during organ perfusion experiments. J. Gibbon, Jr. subsequently uses this type of pump for early laboratory development of heart-lung apparatus.

1929 --- S. Brukhonenko and S. Tchetchuline (Russia) maintain temporary function of guillotined dogs' heads using donor lungs for gas exchange and a bellows-type pump for blood circulation.

1934 --- M.E. DeBakey (New Orleans) describes dual-roller pump for transfusion of blood. This device subsequently becomes the most widely used type of blood pump for clinical applications of cardiopulmonary bypass and hemodialysis.

1937 --- V. Demikhov employed an extracorporeal assist device for 5.5 hours to substitute for the cardiac function of a dog.

1939 --- W. Thalheimer (New York) performs the first hemodialysis of a dog using cellophane membrane and heparin anticoagulation.

1939 --- Robert E. Gross of Boston performs the first successful ligation of a patent ductus arteriosis.

1940 --- Heparin is used for the first time in human patients by Gordon Murray of Toronto.

1943 --- W. Kolff (Kampen, The Netherlands) develops a rotating drum artificial kidney and later the Kolff-Brigham dialyzer (designed and constructed in Boston), which becomes the standard throughout the 1950s.

1945/6 --- N. Alwall (Lund, Sweden) develops first stationary drum artificial kidney and the first artificial ultrafiltration kidney capable of negative pressure and hydrostatic ultrafiltration.

1945/6 --- G. Murray (Toronto) develops a stationary drum artificial kidney.

1949 --- The Skeggs-Leonards kidney, designed by L. Skeggs and J. Leonards, is the first practical flat-plate dialyzer and is used clinically in Cleveland, Ohio.

1951 --- Dubost of Paris replaces the abdominally aorta an aortic homograph.

1952 --- Kolff-Brigham artificial kidney is used by the U.S. Army in 11th field hospital in Korea under unit chief P. Teschan.

1952 --- Arterial graphs made of cloth are first described by Voorhees and Blakemore.

1953 --- J. Gibbon, Jr. (Philadelphia) performs first successful clinical use of the heart-lung machine for cardiac surgery (closure of atrial septal defect).

1954 --- Intra-cardiac surgery is performed by C. Laughton Lillehei using cross circulation from a healthy donor.

1955 --- First meeting of the American Society for Artificial Internal Organs is held at the Hotel Chelsea in Atlantic City, New Jersey with 67 founding members.

1955 --- LANDMARK PUBLICATION : Kolff WJ. The artificial kidney - past, present and future. Tr Am Soc Artif Intern Org 1:1-7, 1955.

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

1955 --- LANDMARK PUBLICATION: Gibbon JH Jr. Artificial heart-lung machines: Chairman's address. Tr Am Soc Artif Intern Org 1:58-62, 1955.

1955 --- W. Kolff and his research team (Cleveland) develop a disposable twin-coil dialyzer.

1950s --- After the brief involvement of Allis-Chalmers and Westinghouse, the Baxter Corporation manufactures the first widely used commercial dialyzing machine - the Baxter/Travenol recirculating U-200 twin-coil dialyzer.

1956 --- G. Clowes (Cleveland) develops the first successful membrane oxygenator-by 1960s further laboratory research studying function and improvement of membrane lungs is undertaken by Kolobow, Peirce, Galletti, Bramson and Hill, Landé and Lillehei, Drinker and Bartlett.

1956 --- LANDMARK PUBLICATION: Clark LC Jr. Monitor and control of blood and tissue oxygenation. Tr Am Soc Artif Intern Org 2:41-45, 1956.

1957 --- W.J. Kolff, T. Akutsu and their research team (Cleveland) successfully implants a hydraulic, polyvinyl chloride total artificial heart in a dog, keeping the animal alive for 90 minutes.

1957 --- DeWall-Lillehei helix reservoir disposable bubble oxygenator is developed at the University of Minnesota and used in a series of 250 patients, which makes cardiopulmonary bypass safe and reliable for other teams worldwide.

1957 --- LANDMARK PUBLICATION: Edwards WS, Tapp JS. Two and a half years experience with crimped nylon grafts. Tr Am Soc Artif Intern Org 3:70-72, 1957.

1958 --- LANDMARK PUBLICATION: Hufnagel C, Villegas A. Aortic valvular replacement. Tr Am Soc Artif Intern Org 4:235-239, 1958.

1960 --- The Quinton-Scribner shunt, developed by W. Quinton and B. Scribner in Seattle, Washington, makes chronic renal dialysis possible.

1960 --- LANDMARK PUBLICATION: Quinton W, Dillard D, Scribner BH. Cannulation of blood vessels for prolonged hemodialysis. Tr Am Soc Artif Intern Org 6:104-113, 1960.

1960 --- LANDMARK PUBLICATION: Scribner BH, Buri R, Caner JEZ, Hegstrom R, Burnell JM. The treatment of chronic uremia by means of intermittent hemodialysis: A preliminary report. Tr Am Soc Artif Intern Org 6:114-122, 1960.

1960 --- R. Stewart develops first hollow fiber dialyzer.

1960 --- First successful intracardiac prosthetic valve operations are conducted by Albert Starr of Portland, Oregon.

1962 --- Cimino and Brescia develop the subcutaneous arterio-venous shunt for chronic hemodialysis.

1962 --- The first successful kidney transplant in unrelated humans is performed by Joseph Murray of Boston.

1963 --- LANDMARK PUBLICATION: Kolobow T and Bowman RL. Construction and evaluation of an alveolar membrane heart lung. Tr Am Soc Artif Intern Org 9:238-245, 1963.

1963 --- LANDMARK PUBLICATION: 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 Org 9:358-362, 1963.

1963 --- D. Liotta and C.W. Hall (Houston) fabricate a tubular left ventricular assist device (LVAD), which is implanted by S. Crawford and M.E. DeBakey, but the patient does not survive. The Smithsonian's National Museum of American History, Artificial Organ Collection has this LVAD, donated by Dr. Hall.

1964 --- Established by the National Heart and Lung Institute, the U.S. Artificial Heart Program, led initially by F. Hasting and later C. Dennis and J. Watson, aims to encourage and support further research and development of cardiac replacement devices (L. Harmison, P. Frommer and F. Altieri all serve important periods of time as Acting Chief for the Total Artificial Heart program).

1964 --- LANDMARK PUBLICATION: 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 Org 10:213-217, 1964.

1964 --- Proportioning pump dialysis machine with safety monitors developed in Seattle. First longterm unattended overnight dialysis with this machine begun in Seattle.

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

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

1966 --- A. Kantrowitz (New York) successfully implants into a patient an aortic U-shaped auxiliary ventricle intended as destination therapy for congestive heart failure.

1966 --- M.E. DeBakey (Houston) performs the first successful clinical implantation of a ventricular assist device (a pneumatically-driven paracorporeal diaphragm pump) in a 37-year-old woman who cannot be weaned from cardiopulmonary bypass following aortic and mitral valve replacement. She is supported for 10 days and discharged in less than a month. The original pump implanted in this patient was made by D. Liotta with the help of engineers from Rice University. Later, this pump is refined, and it is called the BCM-Rice pump. A prototype pump is available at the International Center for Medical Technologies in Houston, Texas.

1967 --- The first human cardiac transplant is carried out by Christian Barnard of South Africa.

1967 --- The first clinical use of the capillary fiber kidney occurs, developed by R. Stewart, and thereafter becomes universally used for long-term hemodialysis.

1967 --- The double-leaflet prosthetic cardiac valve described by Lillehei and Kaster at ASAIO.

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

1967 --- LANDMARK PUBLICATION: 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 Org 13:62-76, 1967.

1967 --- A. Kantrowitz demonstrates clinical effectiveness of the intra-aortic balloon pump in cardiogenic shock patients, with its potential for treatment in acute heart failure.

1968 --- The first successful human liver transplant is reported by Thomas Starzl of Denver.

1968 --- A nuclear powered energy cell for implantable cardiac devices in animals is described by J. Norman at ASAIO.

1968 --- LANDMARK PUBLICATION: Kantrowitz A, Tjonneland S, Krakauer J, Butner AN, Phillips SJ, Yahr WZ, Sharpiro 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 Intern Org 14:344-348, 1968.

1968 --- LANDMARK PUBLICATION: 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 Org 7:286-295, 1961.

1969 --- D.A. Cooley, in the first clinical application of the total artificial heart, implants a pneumatically-powered heart designed by D Liotta (from the laboratory of M.E. DeBakey) as a bridge-to-transplantation into a 47-year-old male who survives 64 hours on the TAH and 32 hours following transplantation.

1969 --- LANDMARK PUBLICATION: Cooley D, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milam RC. First human implantation of cardiac prosthesis for staged total replacement of the heart. Tr Am Soc Artif Intern Org 15:252-263, 1969. (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 Org 15:245-251) 1969.

1970 --- LANDMARK PUBLICATION: 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 Org 16:207-212, 1970.

1971 --- A. Kantrowitz implants the dynamic aortic patch (now called the Kantrowitz CardioVad ) in a patient with terminal heart failure. This 63-year-old man is the first patient to be discharged to home with a cardiac assist device intended as destination therapy for congestive heart failure.

1972 --- End-Stage Renal Disease (ESRD) Act passes in the USA ensuring federal support for chronic kidney disease management.

1972 --- J.D. Hill, T.G. O'Brien and others (San Francisco) report first successful clinical case using extracorporeal membrane oxygenation (ECMO) for respiratory failure.

1974 --- LANDMARK PUBLICATION: Dobell WH, Mladejovsky MG. The directions for future research on sensory prostheses. Tr Am Soc Artif Intern Org 20:425-429, 1974.

1974 --- Lung Division of the National Heart and Lung Institute proposes a multicenter prospective randomized study of ECMO in adult respiratory failure; study begins in 1975.

1975 --- Five different membrane oxygenators for ECMO are manufactured and used, including the Kolobow Sci-Med, the Landé-Edwards, the Peirce-GE, the Bramson, and the Kolobow "Teflo".

1975 --- R.H. Bartlett, A.B. Gazzaniga and their colleagues (University of California, Irvine) report first successful clinical case of neonatal ECMO ("Esperanza").

1975 --- LANDMARK PUBLICATION: Bartlett RH, Gazzaniga AB, Jeffries MR, Huxtable RF, Haiduc NJ and Fong SW. Extracorporeal membrane oxygenations (ECMO) cardiopulmonary support in infancy. Tr Am Soc Artif Intern Org 22:80-93, 1976.

1975 --- The first NIH-sponsored multi-center clinical trial for temporary support in acute ventricular dysfunction (primarily post-cardiotomy), utilizing the model 7 and model 10 Axio-symmetric LVADs (Thermo Electron Corp) and Pierce-Donachy LVAD (Thoratec).

1976 --- The United States Food and Drug Administration (FDA), established in 1931, begins regulating medical devices with passage of the 1976 Medical Device Amendments to the Food, Drug & Cosmetic Act, which seeks to provide "reasonable assurance of safety and effectiveness" for all medical devices.

1977 --- LANDMARK PUBLICATION: 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 Org 23: 13-16, 1977.

1977 --- The Heart and Vascular Division of the National Heart and Lung Institute issues a Request for Proposals (RFP) for components of a totally implantable LVAD, and subsequently awards multiple contracts, establishing the current generation of pulsatile systems.

1978 --- LANDMARK PUBLICATION: 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 Org 24: 98-103, 1978.

1978 --- Continuous ambulatory parenteral dialysis is reported by Oreopoulous at ASAIO.

1978 --- BioMedicus Biopump disposable centrifugal pump (which was originally designed as an artificial heart by H. Kletschka) becomes commercially available as an alternative to the roller pump for cardiopulmonary bypass.

1979 --- Continuous arterial venous hemofiltration is described by Kramer of Goettingen, Germany.

1980 --- Continous AV hemofiltration is used for acute renal failure by Paganini of Cleveland.

1981 --- LANDMARK PUBLICATION: Malchesky PS, Asanuma Y, Smith JW, Kayashima K, Zawicki I, Werynski A, Blumenstein M, Nosé Y. Macromolecule removal from blood. Tr Am Soc Artif Intern Org 27:439-44, 1981.

1982 --- W. DeVries (Salt Lake City) implants the pneumatic Jarvik-7 version of the TAH developed by W. Kolff and coworkers at the University of Utah as a permanent cardiac replacement into patient Barney Clark who survives 112 days with the device.

1982 --- Extracorporeal CO2 removal is described by Kolobow.

1983 --- LANDMARK PUBLICATION: 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 Org 29:81-87, 1983.

1984 --- In the first successful clinical application of an electrically-powered, implantable system, the Novacor LVAS developed by P. Portner is implanted in patient Robert St. Laurent, representing the first successful bridge-to-transplantation.

1984 --- The role of starvation and nutrition in mortality from acute renal failure is described by Mault at ASAIO.

1985 --- Crossover year during which one-half of all cardiopulmonary bypass procedures in the USA are performed with disposable membrane oxygenators, one-half with bubble oxygenators.

1986 --- An artificial liver using porcine hepatitides is described by DeMetriou.

1987 --- Bard cardiopulmonary support system (CPS ) introduced for rapid deployment, portable, percutaneous access for cardiac emergencies.

1988 --- The axial-flow blood pump is described by Wampler at ASAIO.

1994 --- FDA approval of the pneumatically-driven HeartMate LVAD (Thermo Cardiosystems, Inc.) for bridge to transplantation (the first pump with textured blood-contacting surfaces).

1996 --- REMATCH Trial (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart failure, E Rose principal investigator) initiated with HeartMate VE (Thoratec Corp.). Results published in 2002 showed mortality reduction of 50% at one year as compared to patients receiving optimal medical therapy.

1998 --- Simultaneous FDA approval of HeartMate VE (ThermoCardiosystems) and Novacor LVAS (Baxter Healthcare Corp), electrically-powered, wearable assist systems for Bridge to Transplantation, utilized in more than 4,000 procedures to date.

1998 --- First clinical application of next-generation continuous-flow assist devices. DeBakey (Micromed Inc.) axial-flow pump implanted by R. Hetzer, G. Noon and M. DeBakey.

1999 --- First clinical application of a fully-implantable circulatory support system. LionHeart LVAS implanted in 67 year-old male recipient by R. Koerfer and W. Pae.

2001 --- The AbioCor totally implantable, electrically-powered TAH is implanted into patient Robert Tools by L. Gray and R. Dowling (clinical trial is ongoing.).

2002 --- FDA approval of the HeartMate VE LVAD for permanent use (Thoratec Corp.).