American Society for Artificial Internal Organs (ASAIO) Abstracts for the 50th Anniversary Conference. Washington, DC, USA, June 17-19, 2004.
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Animals↗
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Surface abnormalities and conduit characteristics as a cause of blood trauma in artificial internal organs. The interaction of fluid-dynamic, physiochemical and cell biological reactions in thrombus formation.
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Artificial Organs↗
Progress and future perspectives in mechanical circulatory support.
Progress in several types of artificial organs in the cardiovascular field has significantly contributed to advancements in cardiac surgery. Due to the progress of high technology in fields other than medicine, both cardiac surgery and artificial organs have shown rapid and remarkable advances. In recent years, several types of blood pumps have been developed that are widely used not only as the main pump of cardiopulmonary bypass but also for circulatory support of postcardiotomy cardiogenic shock. In this article, the progress and current status of percutaneous cardiopulmonary support systems and ventricular assist devices (VADs) are described. In addition, new centrifugal and axial pumps, which are compact and implantable clinical use devices, are introduced. I believe that by making developments toward the clinical application of artificial hearts or VADs, not only in Japan but also in cooperation with colleagues at various institutions throughout the world, we will be able to make some contributions to the progress in the field of cardiac surgery. In the 20th century, medical research showed remarkable advances, mainly in medical electronics and pathophysiology. However, in the next century, we have to focus on other research fields, namely artificial organs and gene technology.
Cardiopulmonary Bypass↗
ASAIO presidential address.
ASAIO has a proud heritage and a list of many accomplishments. It has given birth to many highly specialized societies and meetings. These changes and new developments in other fields have diverted it from being mainly a kidney society to being more multidisciplinary than ever before. Although meeting attendance declined for a number of years, the productivity of the society did not. Now attendance is increasing, and the number of submitted abstracts has exceeded all past records. Increasing activity in ASAIO may reflect the awareness of the need for a multidisciplinary meeting in this explosive era of artificial organ development. ASAIO can and should play a major role in fostering artificial organ research and development in the years to come. I am confident that it has the strengths to accomplish many important goals. I am very proud to have served as President of this society with a marvelous past and a promising future.
Artificial Organs↗
Design and development of an artificial implantable lung using multiobjective genetic algorithm: evaluation of gas exchange performance.
In this study, we constructed an automatic optimization system applying the multiobjective genetic algorithm (MOGA) and developed an artificial implantable lung possessing antithrombogenicity and high gas exchange performance based upon fluid dynamics. This system consists of a three dimenstional CAD system, computational fluid dynamics software, and the multiobjective optimization tool modeFRONTIER (ESTECO CO., Trieste, Italy). The objectives were to minimize the volume of the region having a flow rate of less than 0.5 mm/s by assuming that thrombus formation occurs at this limit (ObjTF) and to minimize the standard deviation of the flow rate in the hollow fiber to obtain high gas exchange performance (ObjGEP). In optimization 1, the arc heights (six variables) and the distance between cross-sections (two variables) were used as design variables in the inflow and outflow portions. In optimization 2, the edges (two variables) of the inflow and outflow portions were optimized in the resulting designs from optimization 1. The optimum designs were manufactured using the rapid prototyping system and were examined by evaluating gas exchange performance (ObjGEP) in vitro. Gas exchange performance increased as the improvement ratio of ObjGEP became higher. For the optimum design (improvement ratio of 74.8% for ObjGEP), O2 transfer increased by an average of 18.4%, and CO2 transfer increased by an average of 40.5% when compared with the original design. The results suggest that this system was not only effective for reducing the time, cost, and labor of developing artificial organs but was also useful as a design and development support system for high performance artificial organs for transplantation.
Algorithms↗
Energy transmission across intact skin for powering artificial internal organs.
The prototype for a transcutaneous energy transmission system (TETS) meets the engineering goals of high efficiency, limited heating of surrounding tissues due to losses in implanted components, and excellent resistance to misalignment and uncoupling of the coils. Higher efficiencies, reduced thermal generation, and lighter implanted components are the goals of future designs. Improvements will be made based on the findings of a complete in vitro electrical characterization of the present system, varying operating frequency, the number of turns in the 2 coils, and the voltages and currents in the 2 coils. The results of short-term in vivo studies indicate that the temperature rise in tissues surrounding the implanted components is not excessive, that the layer of cutaneous tissue covering the secondary coil is viable and that the thickness of the tissue separating the 2 coils stabilizes after about 2 wks. Definitive statements await the results of in vivo studies lasting longer than 6 mos. Similarly, an evaluation of the effectiveness of butyl as a moisture barrier awaits the results of long-term in vivo, and in vitro immersion test.
Animals↗
New technologies for respiratory assist.
"The artificial lung especially has lingered behind progress with artificial hearts and ventricular assist devices, not because the need for lungs has not been recognized, but because we have not had a full understanding of the engineering problems and the unique material requirements until recent years." Brack Hattler, MD PhD. The development from the first clinical use of haemodialysis over five decades ago to widespread chronic treatment took more than two decades. The histories of other artificial organ technologies, such as artificial hearts, follow similar long development paths. For five decades, due to a lack of technology, artificial lungs have been limited to use with a heart-lung machine for cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO). The advent of pumpless biocompatible artificial lungs will open new treatment options for patients with acute or chronic lung failure.
Artificial Organs↗
Effect of wall hardness on hemolysis.
One of the major problems for artificial organs to develop and to improve is the reduction of hemolysis. The optimum designing of less hemolysis artificial organs is achieved through computational analysis and flow visualization techniques. However, it is impossible to know the quantitative relation between hemolysis and these analytic data. Thus, in vitro studies were performed to estimate these devices on hemolysis because there is no standard for designing these devices with less hemolysis. Therefore, it is essential to reveal the relation between blood flow behaviors and hemolysis. Previous studies reported that hemolysis was caused by a combination of physical factors. In particular, shear stress, pressure, and other fluid dynamical effects were shown to induce hemolysis. In another fluid dynamical experiment reported, the collision flow against the sanded wall was considered the most important factor that directly effected blood damage, which led to hemolysis. The blood flow impact of the collision against the wall effected serious damage to red blood cells. The objective of this study was to point out the relationship between physical force (pressure) in collision flow and hemolysis. In vitro tests using bovine blood and a circulation model that included a jet flow that collides against a wall were conducted. In these tests, we changed the material of the wall by replacing silicone rubber of various thicknesses. The thickness of the silicone rubber is inversely proportional to its hardness. The results show that the increasing rate of hemolysis was lower when the surface was coated by silicone rubber. In conclusion, we considered that it is possible to reduce hemolysis by adjusting the hardness of the material and contacted blood flow.
Animals↗
Implantable artificial lung. Preliminary report.
The ultimate treatment of chronic respiratory insufficiency is pulmonary replacement by an artificial organ, homologous lung transplantation, or chronic paracorporeal respiratory supplementation. The woven capillary membrane oxygenator appears to be a major development toward implantable artificial organs. The four units tested are made up of screens 3.5 by 4.0 cm. of capillary tubing 0.3 mm. I.D. by 0.64 mm. O.D. assembled into rectangular blocks. Units made up by five, ten, twenty, and forty screens have been assembled and tested according to the protocol suggested by Galletti. The maximum oxygen transfer rate with blood was 48 ml. per minute per square meter. Water carbon dioxide transfer rate was 23.1 ml. per minute per square meter. The pressure drops in the liquid phase were 8.5, 15.3, 13.8, 17.6 mm. Hg at 1 L. per minute flow. These results indicate that the woven capillary membrane lung is an acceptably efficient oxygenator. The characteristics of design and performance suggest that this oxygenator can be made to be implanted into the chest or used as a paracorporeal respiratory assistance device.
Artificial Organs↗
Polydisperse dextran as a diffusing test solute to study the membrane permeability of alginate polylysine microcapsules.
Applications of alginate polylysine (APL) microcapsules in cell culture engineering and hybrid artificial organs require strict control of membrane permeability. For example, hybrid artificial organs must permit the diffusion of smaller molecules including peptides and proteins and the exclusion of leucocytes and immunoglobulins (MW > 150,000). Single molecular weight solutes such as proteins have been used to study the molecular weight cut-off of the membrane. A new approach that uses a heterogenous mixture of dextrans of different molecular weights: -MW 10,000-500,000 as a test solute in diffusion experiments is described. Intra/extra capsular changes in concentration and molecular weight distribution of the heterogenous dextran mixture are monitored and determined by high performance gel chromatography. MW can then be related to diffusional Stokes radius, a more useful parameter when comparing permeability of cell membrane to different test solutes.
Alginates↗
Surviving and proliferating faculty of fibroblasts cultured under no-serum and poor nutritional conditions. The basic study on hybridation of cultured cells with an artificial matrix.
BACKGROUND: In this study, we measured survival periods of fibroblasts cultured under conditions providing minimal nutrition. This investigation aims to develop the high affinity hybrid artificial organs on tissues or organs finally. METHODS: Dermal fibroblasts were inoculated on 96-well multiplate according to routine technique. The medium of these cells maintained for 24 hours replaced the new DME medium containing 10% FBS (group 1) or without FBS (group 2) and then cultured for 10 days without medium change. The surviving cell numbers were measured using MTS assay. RESULTS: Surviving cell numbers of both groups decreased progressively during the 10-day assay period. Overall 25-40% of the fibroblasts survived for at least 10 days. It decreased significantly, however, in group 2 from day 2 through day 4 as compared to group 1. In contrast, the cell number decreased in group 1 to a greater extent than in group 2 after day 6. When the cells that survived until day 10 were then cultured with fresh DME medium containing 10% FBS for 3 more days, the cell numbers returned to 50-100% of the initial level CONCLUSIONS: These results suggest that fibroblasts cell function is maintained under poor nutritional conditions, i.e., without serum, possibly via an autocrine or paracrine mechanism. These data could contribute much to the research of hybrid artificial organs, including an artificial trachea, in which hybridization of cultured cells with artificial matrices remains to be a basic process, and has to serve in bloodless postimplantation period.
Cell Count↗
Chlorine dioxide gas sterilization of oxygenators in an industrial scale sterilizer: a successful model.
Artificial organ oxygenators, with large surface areas and complicated structures, were sterilized using chlorine dioxide gas in an industrial scale sterilizer. Bacillus subtilis var. niger ATCC 9372 biological indicators (BI) (10(6) spores/BI) planted in the artificial organs were reproducibly sterilized in a designed cycle schedule with a 30-min dwell time with a chlorine dioxide gas concentration of approximately 30 mg/L in 80 to 85% relative humidity at 30 degrees C. The D value (time required for 90% spore inactivation under specific conditions) was estimated to be 4.4 min. Chlorine dioxide was not detected after post-sterilization aeration. The intravenous median lethal dose (LD50) of chlorine dioxide derivatives, chlorite and chlorate, in rats was found to be 112.8 and 2,228.6 mg/kg, respectively. In an immediate hypersensitivity test, chlorine dioxide gas-treated ovalbumin and bovine serum albumin, unlike ethylene oxide gas-treated proteins, did not cause sterilant-specific IgE-mediated hypersensitivity reactions in rats. Results of an Ames mutagenicity test on chlorine dioxide and on the extracts of the chlorine dioxide gas-exposed oxygenators were negative.
Animals↗
Changing attitude to organ donation and transplantation in university students during the years of medical school in Italy.
UNLABELLED: The shortage of organ donations is a major limiting factor in transplant programs. Since a favorable attitude of health professionals to organ donation can positively influence the decision of families of potential donors, educating physicians early in their careers may become crucial in this setting. The aim of this study was to compare medical student opinions on organ donation and transplantation at different stages in their undergraduate career. METHODS: Medical students were prospectively surveyed in their first and fourth years by an anonymous 10-item questionnaire. RESULTS: The 100 of 195 (51.3%) students completed both questionnaires including 29 men, of an overall cohort mean age 23.7 (range, 22-32 years). 91% of the students had attended classical or scientific high school and 83% were Catholic. Their attitude to transplantation remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth year students would accept an human donor organ or an artificial organ (vs 95% of first year) and 91% would accept an animal organ (vs 84%). The students showed a positive attitude to organ donation (96% vs 91%, fourth vs first year). Most of them were prepared to donate their organs after death (88% vs 87%). 63% of the fourth year students signed a donor card. In conclusion, medical student attitudes to organ donation and transplantation are highly positive, but do not improve during the first 3 years of Medical School. An educational program is therefore needed.
Adult↗
Selected aspects of the microencapsulation of mammalian cells in HEMA-MMA.
Microencapsulation of live mammalian cells is one means of creating hybrid artificial organs, like an artificial pancreas or an artificial liver. In addition to creating and developing the methodologies for enclosing cells within the appropriate semipermeable and biocompatible membranes, novel techniques are needed to assess the various features of the resulting capsules. The small size of a capsule or its heterogeneity can lead to additional complexities that go beyond the problem of examining cell behavior in the presence of biomaterials. These problems are illustrated here by comparison of protein release by microencapsulated HepG2 cells within large and small HEMA-MMA (hydroxyethyl methacrylate-methyl methacrylate) capsules, by assessment of the effect of processing conditions on HEMA-MMA microcapsule permeability to horseradish peroxidase at the individual capsule level, and by a confocal microscopy technique for assessing intracapsule cell viability.
Animals↗
Dialysis membranes for blood purification.
All of the artificial membranes in industrial use, such as a reverse-osmosis membrane, dialysis membrane, ultrafiltration membrane, microfiltration membrane and gas separation membrane, also have therapeutic applications. The most commonly used artificial organ is the artificial kidney, a machine that performs treatment known as hemodialysis. This process cleanses the body of a patient with renal failure by dialysis and filtration, simple physicochemical processes. Hemodialysis membranes are used to remove accumulated uremic toxins, excess ions and water from the patient via the dialysate, and to supply (deficit) insufficient ions from the dialysate. Dialysis membranes used clinically in the treatment of patients with renal failure account for by far the largest volume of membranes used worldwide; more than 70 million square meters are used a year. Almost all dialyzers now in use are of the hollow-fiber type. A hollow-fiber dialyzer contains a bundle of approximately 10000 hollow fibers, each with an inner diameter of about 200 microm when wet. The membrane thickness is about 20-45 microm, and the length is 160-250 mm. The walls of the hollow fibers function as the dialysis membrane. Various materials, including cellulose-based materials and synthetic polymers, are used for dialysis membranes. This paper reviews blood purification, hemodialysis and dialysis membranes.
Biocompatible Materials↗
[Future of surgery].
Most current surgical techniques were developed in the 20th century, especially during the past 50 years. Open heart surgery, vascular surgery, neonatal surgery, organ transplantation and artificial organs, microsurgery, intravenous hyperalimentation, and, more recently, endoscopic surgery emerged during the past five decades. Many of the dreams of surgeons in the past have now been realized. These advances in surgery were made possible by the development of new technologies and instrumentation, but most importantly were initiated by the pioneering spirit of surgeons. This will continue on in the next century, since history shows that classical or conventional treatment modalities are constantly changing and being replaced by new ones based on new ideas and technologies. In this age of molecular biology, gene therapy, computer science, and the Internet, the pace of change in medicine and surgery will accelerate. Systems for training and communications, and even medical ethics, will inevitably change. We may not be able to predict precisely the future changes in surgery and surgeons, but we must be prepared for them and steer the future of surgery for the benefit of patients.
Forecasting↗
[Perspectives on regenerative therapy].
Organ transplantation and artificial organs are the only effective treatments for loss of organ and tissue function. These treatments, however, are associated with serious problems such as a critical shortage of donor organs, rejection, the need for life-long immunosuppression, and unstable biocompatibility. These shortcomings have stimulated the development of tissue engineering. Tissue engineering is defined as an interdisciplinary field that applies the principles of engineering and the life sciences to the development of biological substitutes that restore, retain, or improve tissue function. Tissue engineering is composed of three factors: cells; growth factors; and scaffolds. Regenerative medicine includes two important fields: tissue engineering; and regenerative biology. Regenerative therapy is a newly developed medical therapy based on the research results of regenerative medicine. The fields of regenerative therapy includes broad areas of basic and clinical sciences, bioethics, and medical economics in addition to the area of regenerative medicine. Cell sources and cell expansion are important issues in regenerative medicine. Great efforts are being made to isolate and identify the characteristics of stem cell populations of various tissues. The use of stem cells may provide an almost limitless supply of cells for transplantation. Although there are still many important issues to be resolved, regenerative medicine has been making rapid progress using a multidisciplinary approach. The success of this approach will lead to the widespread application of regenerative therapy and may ultimately be able to replace lost tissue function in the 21st century. We should, however, keep in mind the importance of bioethics in using any new therapy.
Cell Transplantation↗
Solute washout experiments for characterizing mass transport in hollow fiber immunoisolation membranes.
The transport characteristics of immunoisolation membranes can have a critical effect on the design of hybrid artificial organs and cell therapies. However, it has been difficult to quantitatively evaluate the desired transport properties of different hollow fiber membranes due to bulk mass transfer limitations in the fiber lumen and annular space. An attractive alternative to existing methodologies is to use the rate of solute removal or "washout" from the annular space during constant flow perfusion through the fiber lumen. Experimental washout curves were obtained for glucose and a 10 kD dextran in two different hollow fiber devices. Data were analyzed using a theoretical model which accounts for convective and diffusive transport in the lumen, membrane, and annular space. The model was in good agreement with the experimental results and provided an accurate measure of the effective membrane diffusion coefficient for both small and large solutes. This approach should prove useful in theoretical analyses of solute transport and performance of hollow fiber artificial organs.
Artificial Organs↗