bluuebunny/crossref_metadata_2025 huggingface dataset:
Xenotransplantation of Fetal Porcine Hepatocytes in Rats Using a Tissue Engineering Approach
Authors: Elçin Y. Murat , Dixit Vivek , Lewin Klaus , Gitnick Gary
Published: March 2003

Hepatocytes can be successfully transplanted into highly vascular sites such as the spleen, liver, and lungs. Subcutaneous sites lack adequate vascularization to nutritionally support transplanted hepatocytes. We recently reported that matrix‐immobilized angiogenic growth factors, e.g., endothelial cell growth factor (ECGF), can induce a high degree of neovascularization. Using this technique, we explored the possibility of transplanting isolated fetal porcine hepatocytes to create liver tissue organoids at a specific subcutaneous site. We evaluated chitosan as a scaffold biomaterial because of its structural similarity to glycosaminoglycans; glycosaminoglycans play a critical role in cell attachment, differentiation, and morphogenesis. Freshly isolated fetal porcine hepatocytes (FPH) (viability greater than 97%) were cultured on modified chitosan scaffolds and transplanted into rat groin fat pads with or without ECGF‐induced neovascularization. Cell density and attachment kinetics on chitosan were examined by scanning electron microscopy (SEM) and quantified using a flavianic acid binding assay. Hepatocyte viability and liver organoid formation were examined immunohistochemically. FPH transplanted without prior neovascularization died within 1 day posttransplantation. When transplanted after ECGF‐induced neovascularization, FPH thrived for at least 2 weeks and formed liver tissue like structures. Immunohistochemical analysis revealed the presence of hepatocyte‐specific cytokeratin staining as well as the presence of α‐fetoprotein. Light microscopy and SEM revealed that FPH did not change their morphology after attachment to the chitosan surfaces. Thus, chitosan‐based biomaterial surfaces have good hepatocyte attachment properties. However, extensive neovascularization is essential for hepatocyte survival and organoid formation. In the future, chitosan‐based biomaterials may be useful as scaffolds for creating liver tissue organoids.
Hepatitis C Virus Infection in Dialysis: A Continuing Problem
Authors: Pereira Brian J.G.
Published: March 2003

Patients on chronic dialysis are at increased risk of acquiring parenterally transmitted hepatitis viruses from blood product transfusions or nosocomial transmission in hemodialysis units, and biochemical abnormalities in liver function are seen in 10–44% of patients on chronic hemodialysis. In the past, hepatitis B virus (HBV) was the major cause of parenterally transmitted viral hepatitis in dialysis patients, and the remaining cases were attributed to non‐A, non‐B hepatitis (NANBH). The discovery of the hepatitis C virus (HCV) has shed light on the cause and clinical course of NANBH in patients on dialysis. The current debate is focused on strategies to reduce the transmission of HCV among dialysis patients and to lessen the consequences of liver disease among patients already infected.
Importance of Sodium Dodecyl Sulfate Pore‐Graduated Polyacrylamide Gel Electrophoresis in the Differential Diagnostic of Balkan Nephropathy
Authors: Ikonomov Valentin , Melzer Heinrich , Nenov Veselin , Stoicheva Adriana , Stiller Siegfried , Mann Helmut
Published: March 2003

Balkan nephropathy (BN) is an endemic disease, which leads to end‐stage renal failure and artificial renal replacement therapy. Pathologically it is characterized by progressive interstitial nephritis in a large population of villages situated in the proximity of a bend of the Danube up to a distance of 100 km from the river in several parts of Bulgaria, Romania, and the former Yugoslavia. The urinary proteins of 19 patients with BN from the region of Vratza, Bulgaria were examined using ultrathin layer sodium dodecyl sulfate (SDS) pore‐graduated polyacrylamide gel electrophoresis (PAGE) and silver staining. The documentation of urinary proteins pattern was performed using laser densitometry and consecutive electronic processing for the purpose of characterizing and quantifying protein excretion. Our results show that the proteinuria of BN is predominantly tubular, consisting of low molecular weight species (10–65 kilodaltons). The amount of tubular protein changes with the progression of the disease. SDS‐polyacrylamide gel electrophoresis (PAGE) is a diagnostic method for early diagnosis of tubular failure in BN. Using our method of SDS‐PAGE, tubular failure can be detected even at a total protein concentration below 0.1 g/L and when the serum creatinine concentration is normal. Additionally, our method of SDS‐PAGE supports the differentiation of BN from glomerular disease.
Survival of Patients on Chronic Hemodialysis: Single Center Experience
Authors: Polenakovik  , Sikole  , Stojcev  , Spasovski  , Amitov  , Nikolov  , Masin  , Klinkman
Published: March 2003

Patient survival from our hemodialysis (HD) center over the past 11 years was analyzed. Four hundred four patients, 212 female and 192 male, were treated by chronic intermittent HD. Patients were offered standard acetate‐cellulosic membranes of 1.0–1.3 m2. During this period 181 patients died. One hundred three patients were transferred to other HD centers, and some were transplanted. One hundred twenty patients are still on HD treatment. The 5 year survival rate of patients treated in our center was 58%. Women lived longer than men, and age correlated significantly with survival rate. Patients with chronic glomerulonephritis and adult polycystic kidney disease had the best survival rates while diabetic patients and those with post hypertensive nephropathy had the poorest survival rates. Forty‐four percent of patients had a cardiac related cause of death, cerebrovascular accident was the cause in 15%, and 11 % died due to septic condition (infection) while 8% died due to liver disease.
Hypotransferrinemia of Chronically Hemodialyzed Patients
Authors: Kirschbaum Barry
Published: March 2003

Abstract: Increasingly, the iron needs of hemodialysis patients receiving erythropoietin are being met by infusions of intravenous iron guided by laboratory tests to measure body iron availability. The interpretation of assays based on ferritin and transferrin must take into account the effect of inflammation on both proteins and malnutrition on the latter. In our chronic hemodialysis population, hypotransferrinemia was present in greater than 90% of the patients. Using statistical methods and laboratory studies, we sought to identify the principal reasons for the high prevalence of hypotransferrinemia. We observed that transferrin levels were disproportionately low relative to albumin and prealbumin and correlated inversely with ferritin levels. There was no correlation between transferrin and the soluble transferrin receptor. After the infusion of 900 mg of iron, transferrin saturation increased and total transferrin decreased so that unsaturated iron bonding capacity decreased as well. Ferritin concentrations increased significantly after iron loading. Attempts to demonstrate activation of the patients' antioxidant mechanisms associated with iron infusion were negative. We concluded that the low transferrin may be principally the result of diminished synthesis related to the chronic inflammatory status of hemodialysis patients, which favors production of ferritin, but iron and nutritional status may also influence the blood transferrin concentration. These factors make interpretation of transferrin‐dependent assessment of body iron stores unreliable and can result in inadequate or overly aggressive iron‐replacement therapy.
Three Parameters Optimizing Closed‐Loop Control in Sequential Segmental Neuromuscular Stimulation
Authors: Zonnevijlle Erik D.H. , Somia Naveen N. , Abadia Gustavo Perez , Stremel Richard W. , Maldonado Claudio J. , Werker Paul M.N. , Kon Moshe , Barker John H.
Published: March 2003

In conventional dynamic myoplasties, the force generation is poorly controlled. This causes unnecessary fatigue of the transposed/transplanted electrically stimulated muscles and causes damage to the involved tissues. We introduced sequential segmental neuromuscular stimulation (SSNS) to reduce muscle fatigue by allowing part of the muscle to rest periodically while the other parts work. Despite this improvement, we hypothesize that fatigue could be further reduced in some applications of dynamic myoplasty if the muscles were made to contract according to need. The first necessary step is to gain appropriate control over the contractile activity of the dynamic myoplasty. Therefore, closed‐loop control was tested on a sequentially stimulated neosphincter to strive for the best possible control over the amount of generated pressure. A selection of parameters was validated for optimizing control. We concluded that the frequency of corrections, the threshold for corrections, and the transition time are meaningful parameters in the controlling algorithm of the closed‐loop control in a sequentially stimulated myoplasty.
Use of Functional Electrical Stimulation in the Lower Extremities of Incomplete Spinal Cord Injured Patients
Authors: Bajd Tadej , Kralj Alojz , Štefančič Martin , Lavrač Nada
Published: March 2003

After a program of therapeutic electrical stimulation, 3 groups of incomplete spinal cord injured (SCI) patients were identified, those in whom an improvement of both voluntary and stimulated muscle force was observed, those with an increase in stimulation response only, and patients in whom no effect of electrical stimulation training could be recorded. As it is difficult to predict the outcome of the electrical stimulation rehabilitation process, a diagnostic procedure was developed to predict soon after accidents which incomplete SCI patients are candidates for permanent use of a functional electrical stimulation (FES) orthotic aid. The candidates for chronic use of FES are patients with weak ankle dorsiflexors and sufficiently strong knee extensors. These patients are equipped with a single channel peroneal stimulator augmenting dorsiflexion and knee and hip flexion in a total lower limb flexion response. By applying FES to the ankle plantar flexors, the swing phase of walking can be significantly shortened and faster walking obtained.
Functional Electrical Stimulation and Arm Supported Sit‐To‐Stand Transfer After Paraplegia: A Study of Kinetic Parameters
Authors: Kamnik Roman , Bajd Tadej , Kralj Alojz
Published: March 2003

The sit‐to‐stand transfer of paraplegic patients using functional electrical stimulation (FES) of the knee extensors and arm support was analyzed in the study. In a group of 8 completely paralyzed subjects who were trained FES users, kinematic and dynamic parameters were recorded during standing up trials. A contactless optical system was used to assess the human body motion. The forces acting on the human body were measured by multi‐axis force transducers. On the basis of recursive Newton‐Euler inverse dynamic analysis, the forces and torques acting on the body joints were calculated. The joint moments in the lower and upper extremities during the sit‐to stand task are presented in this paper. The influences of the patient's strength, FES training duration, and rising strategy on the joint loading are discussed.
Paraplegia: Prolonged Standing Using Closed‐Loop Functional Electrical Stimulation and Andrews Ankle‐Foot Orthosis
Authors: Davis Ross , Houdayer Thierry , Andrews Brian , Barriskill Andrew
Published: March 2003

One T10 paraplegic male (CS) implanted in 1991 with a Nucleus FES‐22 stimulator has been able to achieve closed‐loop standing for 1 h. The knee angles are monitored by electrogoniometers, resulting in the quadriceps stimulation time being less than 10%. Stance stability is achieved by the Andrews anterior ankle‐foot orthosis (AFO). The use of accelerometers for trunk inclination and vertical acceleration during controlled stand‐to‐sit, diminishes slamming onto the seat. CS does one‐handed tasks with objects of 2.2 kg. In another T10 paraplegic male (FR), surface stimulation was applied over 1.5 years to both femoral nerves at the groin for conditioning and prolonged standing. With quadricep conditioning, 55 Nm at 45 degrees of knee flexion is produced. With the AFO and knee monitoring, FR can stand uninterrupted for up to 70 min and perform one‐handed tasks. In August 1998, he was implanted with the multifunctional Praxis FES 24‐A stimulator for restoration of limb movements, bladder and bowel function, and pressure sore prevention.
MYOSTIM‐FES to Prevent Muscle Atrophy in Microgravity and Bed Rest: Preliminary Report
Authors: Mayr Winfried , Bijak Manfred , Girsch Werner , Hofer Christian , Lanmüller Hermann , Rafolt Dietmar , Rakos Monika , Sauermann Stefan , Schmutterer Christoph , Schnetz Guntram , Unger Ewald , Freilinger Gerhard
Published: March 2003

Long‐term flights in microgravity cause atrophy and morphological changes of skeletal muscles. Training with mechanical devices is insufficient regarding the required time to exercise and space for devices. The objective of this project is to develop a passive training method based on functional electrostimulation (FES) to preserve muscle mass and fiber composition with minimal impairment to the cosmonaut. For a pilot experiment on the MIR space station, a suitable 8 channel FES device was developed. It consists of electrode trousers that carry surface electrodes and cables, 2 interconnected 4 channel stimulators, and a laptop personal computer (PC) for stimulator programming and processing compliance data. An automatic extensive training of 4 muscle groups of the lower extremities is performed for 6 h/day, with 1 s on and 2 s off tetanic contractions at 20–30% of maximum tetanic muscle force. The synchronous activation of antagonists of the thigh and lower leg prevents uncoordinated movements.
Adaptive Restriction Rules Provide Functional and Safe Stimulation Pattern for Foot Drop Correction
Authors: Kostov Aleksandar , Hansen Morten , Haugland Morten , Sinkjær Thomas
Published: March 2003

We report on our advances in sensory feedback data processing and control system design for functional electrical stimulation (FES) assisted correction of foot drop. We have applied 2 methods of signal purification on the bin integrated electroneurogram (i.e., optimized low pass filtering and wavelet denoising) before training adaptive logic networks (ALN). ALN generated stimulation control pulses, which correspond to the swing phase of the impaired leg when dorsal flexion of the foot is necessary to provide safe ground clearance. However, the obtained control signal contained sporadic stimulation spikes in the stance phase, which can collapse the subject, and infrequent broken stimulation pulses in the swing phase, which can result in unpredictable consequences. In this study, we have introduced adaptive restriction rules (ARR), which are initially used as previously reported and then dynamically adapted during the use of the system. Our results suggest that ARR provide a safer and more reliable stimulation pattern than fixed restriction rules.
Vagal Nerve Activity Recording in the Awake Condition for the Control of an Artificial Heart System
Authors: Yambe Tomoyuki , Nanka Shun‐suke , Kobayashi Shin‐ichi , Tanaka Akira , Yoshizawa Makoto , Abe Ken‐ichi , Tabayashi Kouichi , Takeda Hiroshi , Nitta Shin‐ichi
Published: March 2003

To detect useful information for an artificial heart control system, we paid attention to the autonomic nervous system. For stable recording, we used vagal nerve activity in chronic animal experiments using healthy adult goats in an awake condition because this nerve was sufficiently bold and large enough. Vagal nerve discharges were successfully recorded from awake goats. They were synchronized with respiration and responded to the hemodynamic changes induced by drug administration, suggesting that they may provide useful information for an artificial heart control algorithm. For automatic control, some time delay plays a vitally important role. Thus, predictive control for an artificial heart system may be desirable. It may be embodied by the use of autonomic nerve information.
Detection of Suction and Regurgitation of the Implantable Centrifugal Pump Based on the Motor Current Waveform Analysis and Its Application to Optimization of Pump Flow
Authors: Yuhki  , Hatoh  , Nogawa  , Miura  , Shimazaki  , Takatani
Published: March 2003

In this study, a detection algorithm for suction and regurgitation of the centrifugal pump during left heart bypass without relying on external flow or pressure sensors was developed and evaluated in acute studies using adult goats. The detection scheme relies on power spectral density (PSD) analysis of the motor current waveform through which the waveform deformation index (WDI) is obtained. This index is defined as the ratio of the fundamental component of the PSD to the higher PSD components, and its value increases with the deformation of the basic waveform. By assuming that the undistorted motor current waveform can be represented by a pure sine waveform, we theoretically synthesized various waveforms which have different second harmonic components. We were able to synthesize the waveform whose shape was close to the distorted motor current waveform under varying suction levels obtained in a mock loop study. From this study, we came to the conclusion that the WDI value of 0.2 can serve as a threshold level in deciding the suction and regurgitation speeds (rpm) during left heart bypass. In the study using adult goats, we were successful in minimizing both regurgitation and suction when the centrifugal pump speed was adjusted based on the WDI algorithm. The resultant bypass flow ranged from 1.5 to 2.0 L/min which was around 60% of the total flow. Further study is underway to evaluate the applicability of the WDI method in optimizing bypass pump flow.
Flow Balance Between the Left and Right Cardiac Output of an Eccentric Roller Type Total Artificial Heart
Authors: Wada Hideichi , Fukunaga Shintaro , Watari Masanobu , Sakai Hiroshi , Sugawara Yuji , Ochikubo Hiroyuki , Imai Katsuhiko , Shibamura Hidenori , Orihashi Kazumasa , Sueda Taijiro , Matsuura Yuichiro
Published: March 2003

We have made an eccentric roller type total artificial heart (ERTAH). The ERTAH is a positive‐displacement device comparable to a DeBakey roller pump. Its left and right outputs are determined by the size of its blood chambers, and the ratio of its left and right output is almost constant. We focused on an interatrial shunt to achieve left‐right balance. We have conducted numerical simulation, a mock test, and an acute animal experiment to analyze left‐right heart balance during ERTAH operation. Numerical simulation was performed under conditions in which the flow of the left artificial heart was fixed at 6 L/min, the flow of the right artificial heart was varied from 4.8 to 6 L/min, and the interatrial resistance was also varied. The relationship between the interatrial shunt flow rate and the output of the left and right artificial hearts was balanced when the flow of the right artificial heart was at 5.45 L/min. In a mock test, 2 DeBakey roller pumps were connected to the left and right sides of a Donovan mock circulatory system, and an interatrial shunt was created between the inlet ports of the left and right roller pumps. The interatrial resistance of the mock system was varied from 7.7, to 4.3, and to 2.9 mm Hg·min/L when the inner diameter of the interatrial shunt was 6, 8, and 10 mm, respectively. As in the mock test, 2 roller pumps were used to bypass the right and left hearts of a goat weighing 60 kg. The flow rate of the left heart was almost constant (4.7 L/min). The flow of the right heart was approximately 4.1 L/min when the interatrial shunt flow rate was zero. A leading consideration was that the left to left shunt through the bronchial arteries in this goat was approximately 0.6 L/min. In developing the ERTAH, we considered that creating an interatrial shunt between the inlet ports of the ERTAH as well as making a difference between the chamber volumes might be effective in balancing the left‐right sides of the artificial heart.
Issues of Pharmacology in Pediatric Cardiac Extracorporeal Membrane Oxygenation with Special Reference to Analgesia and Sedation
Authors: Burda Gudrun , Trittenwein Gerhard
Published: March 2003

Abstract: Sufficient analgesia, sedation, and paralysis, if necessary, are cornerstones of extracorporeal membrane oxygenation (ECMO) treatment protocols. However, increased distribution volumes, drug absorption by circuit materials, and impaired drug elimination, as well as alternations of cerebral perfusion and blood brain barrier function, result in the markedly altered pharmacodynamics of applied drugs. Today, narcotics combined with benzodiazepines, sometimes enforced by barbiturates, are commonly used in clinical practice. Paralysis is usually achieved by pancuronium or vecuronium. Although these drugs are used widely, actual efficicacy remains uncertain because of the lack of reliable tools to measure pain relief and degree of sedation during ECMO, especially during paralysis. Taking into acount the detrimental effects of insufficient pain relief and inadequate sedation in such unstable patients as children during pediatric cardiac ECMO, further studies on this topic seem urgently necessary.
Augmented Destruction Test with an Electromechanical Pulsatile Total Artificial Heart
Authors: Ohashi Yukio , Andrade Aron , Müller Jürgen , Nosé Yukihiko
Published: March 2003

Abstract: The total artificial heart (TAH) being developed by these authors successfully completed hydrodynamic and hemolysis studies followed by two acute implantations. Before commencing preclinical studies on any device, documentation of the reliability and durability of each component has to be done. This TAH was submitted to a 4 month destruction test under the most severe driving conditions to detect any weak mechanical components of the system. The maximum dP/dt in the left pumping chamber was chosen of more than 15,000 mm Hg/s, which is almost 6 times higher than that of the normal driving condition. The pump was submersed into a water bath that was maintained at 37°C. The TAH was driven in a left master alternative (LMA) variable rate mode at 8 L/min output flow, 15 mm Hg preload, 100 mm Hg left afterload, and 25 mm Hg right afterload. The outflow, pressures, and temperature inside the TAH were monitored. Several stress concentration areas were detected. The connection between the roller nut and support plate proved to be one of the most stressed regions, and a more reliable fixing procedure was required. This portion was redesigned to offer a durable connection. No malfunctions of the actuator or controller were detected throughout the testing duration. No temperature elevation more than 1°C on the center piece of the TAH was demonstrated.
Immobilization of Ligand‐Modified Polyamidoamine Dendrimer for Cultivation of Hepatoma Cells
Authors: Kawase Masaya , Kurikawa Nobuya , Miura Nagamitsu , Shiomi Teruaki , Ozawa Chitose , Higashiyama Shinji , Mizoguchi Tadashi , Yagi Kiyohito
Published: March 2003

Abstract: Cationic polyamidoamine dendrimers are known to be highly branched cascade polymers. The core part of these polymers, tris(2‐aminoethyl)amine, was immobilized onto polystyrene plates to which animal cells do not adhere, using photoreactive 4‐(3‐trifluoromethylazirino) benzoyl‐N‐succinimide (TDBA‐OSu). Cells of a rat hepatoma cell line, H4‐II‐E‐C3, adhered to a surface immobilized with a first‐generation dendrimer probably through interactions between the terminal amino groups of the dendrimer and the cell membranes. The adhered cells were viable, could proliferate, and exhibited urea synthetic activity. The modification of the terminal amino groups with fructose increased the final number of cells obtained after 5 days of cultivation. Multigeneration dendrimers were prepared by repeated linkage of tris(2‐aminoethyl)amine with the amino groups. Theoretically, the number of terminal amino groups available for ligand modification is twice as much for each generation of dendrimer growth. Cells cultivated on multigeneration fructose‐modified dendrimers exhibited enhanced urea synthetic activity. The use of ligand‐modified dendrimers is, therefore, considered to be very promising for the construction of bioartificial organs based on cultivation of the animal cells.
Carotid Intima‐Media Thickness and Plaques in Hemodialysis Patients
Authors: Hojs Radovan
Published: March 2003

Abstract: Atherosclerosis is accelerated in hemodialysis patients. Using B‐mode ultrasonography, we compared intima‐media thickness (IMT) and the prevalence of plaques in the common carotid and internal carotid arteries in 28 randomly selected hemodialysis patients with that in 28 age‐ and sex‐matched normal controls. The IMT values of the common carotid and internal carotid arteries were higher in hemodialysis patients than in controls with more hemodialysis patients having plaques. In hemodialysis patients, there was a relationship between age and IMT in the common carotid arteries, in the area of bifurcation, and in the internal carotid arteries. We found no relationship between IMT and atherosclerotic risk factors or duration of hemodialysis treatment. IMT at all sites correlated with the number of plaques. Age was the only significant determinant for number of plaques. The results indicate that hemodialysis patients showed advanced atherosclerosis in the carotid arteries compared with age‐ and sex‐matched normal subjects.
Use of N‐Butyl‐2‐Cyanoacrylate in Oral Surgery: Biological and Clinical Evaluation
Authors: Pérez Mayra , Fernández Iraida , Márquez Daysi , Bretaña Rosa Mayelín Guerra
Published: March 2003

Abstract: N‐butyl‐2‐cyanoacrylate based tissue adhesive, Tisuacryl, was employed as a nonsuture method for closing wounds in oral surgery. One hundred thirty patients were treated with the adhesive and 30 with suture. The surgical procedures were apicectomy, extraction of molars, and mucogingival grafting. The studied product was well tolerated by the tissue and permitted immediate hemostasis and normal healing of incisions. When Tisuacryl was used as dressing material for donor sites and mucosal ulcerations, pain relief was observed.
Sensorless Controlling Method for a Continuous Flow Left Ventricular Assist Device
Authors: Oshikawa M. , Araki K. , Endo G. , Anai H. , Sato M.
Published: March 2003

Abstract: We originated a novel control strategy for a continuous flow left ventricular assist device (LVAD). We examined our method by acute animal experiments to change the left ventricular (LV) contractility or LV end‐diastolic pressure (LVEDP). To estimate the pump pulsatility without any specific sensor, we calculated the index of current amplitude (ICA) from motor current waveform. The ICA had a peak point (t‐i point) that corresponded closely with the turning point from partial to total assistance, and a trough (s‐i point) that corresponded with the beginning point of ventricular collapse. The pump flow at the t‐i point (Qt‐i) had no component of flow regurgitation. In the evaluation of the effects of preload LVEDP, afterload (mAoP), and contractility (max LV dp/dt), we found that preload was the only parameter that significantly influenced Qt‐i. We concluded that our method could well control continuous flow LVAD by preventing reversed flow and ventricular collapse.
Closed Circuit Cardiopulmonary Bypass with Centrifugal Pump for Open‐Heart Surgery: New Trial for Air Removal
Authors: Morita Masanori , Yozu Ryohei , Matayoshi Toru , Mitsumaru Atsuhiro , Shin Hankei , Kawada Shiaki
Published: March 2003

Abstract: The purpose of this study is to examine the efficiency of venous air removal with a new cardiopulmonary bypass (CPB) circuit design for conventional open‐heart surgeries. A main concern with a closed circuit for open‐heart surgeries is air entrainment into the venous line. A venous filter was placed proximal to the centrifugal pump. The circuit proximal to the centrifugal pump was divided into two lines; one line was attached to the venous reservoir outlet. By clamping the line to the reservoir, this circuit becomes closed. Negative pressure was applied to the purge line connected to the venous reservoir for venous air removal. Micro bubbles were measured at two locations, both distal to the venous and arterial filters. When the injection rate reached 100 ml/min, with the air‐injection over 30 s, micro bubbles greater than 40 μ were observed at the outlet of venous filter. However, there was no micro bubble greater than 40 μ detected at the outlet of arterial filter. Although micro bubbles greater than 40 μ were not detected at the outlet of the arterial filter up to the injection rate of 300 ml/min, when the injection rate reached 400 ml/min, micro bubbles greater than 50 μm were detected distal to the arterial filter. From this examination, we determined that air entrained in the venous line up to approximately 300 ml/min is automatically removed by this method with the pressure‐balanced condition. This pressure balance means that resistance of venous return, gravity siphon, negative pressure by centrifugal pump, and negative pressure applied to the air‐purge line of the filter are balanced; that is, the venous return is sufficient, and the venous reservoir volume is kept stable. From this study we determined that this circuit design efficiently removes the entrained air in the venous line.
Control Strategy for Rotary Blood Pumps
Authors: Ohuchi Katsuhiro , Kikugawa Daiki , Takahashi Kiyofumi , Uemura Masahito , Nakamura Makoto , Murakami Taiji , Sakamoto Tohru , Takatani Setsuo
Published: March 2003

Abstract: The control strategy for ventricular support with a centrifugal blood pump was examined in this study. The control parameter was the pump rpm that determines pump flow. Optimum control of pump rpm that reflects the body's demand is important for long‐term, effective, and safe circulatory support. Moreover, continuous, reliable monitoring of ventricular function will help successfully wean the patients from the ventricular assist device (VAD). The control strategy in this study includes determination of the target pump rpm that can provide the flow required by the body, fine‐rpm‐tuning to minimize deleterious effects such as suction in the ventricle, and assessment of ventricular function for successful weaning from VADs. To determine the target pump rpm, we proposed to use the relation between the native heart rate and cardiac output, and the relation between the pump rpm and centrifugal pump output. For fine‐tuning of the pump rpm, the motor current waveform was used. We computed the power spectral density of the motor current waveform and calculated the ratio of the fundamental to the higher order components. When this ratio was larger than approximately 0.2, we assumed there would be a suction effect in the ventricle. As for assessment of ventricular function, we used the amplitude of the motor current waveform. The control system implemented using a DSP functioned properly in the mock circulatory loop as well as in acute animal experiments. The motor current also showed a good correlation with the ventricular pressure in acute animal experiments.
A Bone Replaceable Artificial Bone Substitute: Osteoinduction by Combining with Bone Inducing Agent
Authors: Suh Hwal , Han Dong‐Wook , Park Jong‐Chul , Lee Dong Hee , Lee Woo Suk , Han Chang Dong
Published: March 2003

Abstract: Bone inducing agent (BIA) isolated from Saos‐2 human osteosarcoma cells was added to an artificial bone substitute composed of 980°C‐heated carbonate apatite (CAp) and Type I atelocollagen (AtCol) extracted from bovine tail skins (88/12 in wt/wt %), and a CAp‐AtCol‐BIA substitute was prepared as an osteoinductive bone substitute. Rat calvaria osteoblasts treated by the isolated BIA demonstrated significantly increased alkaline phosphatase (ALP) activity after 3 days (p < 0.05). In vitro cell attachment and proliferation and ALP activity were investigated for the bone substitute combined with BIA. Osteoblasts cultured onto the surface of the CAp‐AtCol‐BIA substitute demonstrated remarkable morphological changes such as radial spreading, flattening, and projecting filopodia after 5 days. In comparison with the substitute without BIA, osteoblasts grown in the BIA‐combined CAp‐AtCol substitute expressed significantly increased proliferation and ALP activity, respectively (p < 0.05). Both the substitutes combined with and without BIA were implanted into artificial defects created in rabbit radii. After 4 weeks, the CAp‐AtCol‐BIA substitute implanted lesion was completely replaced by regenerated host bone in radiological observation whereas the substitute without BIA was partially resorbed. No histologic abnormalities appeared in the substitute either with or without BIA.
Culture of Porcine Hepatocytes: The Dogma of Exogenous Matrix Revisited
Authors: Lorenti Alicia , Barbich Mariana , Hidalgo Alejandra , Hyon Sung Ho , Sorroche Patricia , Guinle Adolfo , Schenone Andrea , Chamoles Néstor , Argibay Pablo
Published: March 2003

Abstract: The use of exogenous matrices has been described as an essential component in securing the viability and functionality of hepatocytes in vitro whether cultured for extracorporeal devices or cell transplantation. Here we report on the in vitro culture of porcine hepatocytes in polystyrene tissue‐culture flasks without exogenous matrices showing adequate attachment and viability. Cell proliferation was evidenced by uptake of 5‐bromo‐2′‐deoxyuridine, with peaks at Days 2 (19.7 ± 8.5%), 15 (20.8 ± 3.3%), and 35 (21.4 ± 0.3%). Detoxification capacity was assessed by determination of monoethylglycinexylidide, a product of lidocaine metabolism (highest value 156.5 ± 10.1 ng/ml at Day 4), and by diazepam clearance (maximum clearance 66.2% at Day 6). Diazepam metabolite levels were highest at Day 4 both for temazepam and oxazepam (6.5 ± 0.1 and 0.10 ± 0.01, respectively). These results suggest that the need for an exogenous matrix to achieve sustained proliferative activity and differentiated hepatocyte function should not necessarily be considered a sine qua non condition.
Application of Extracorporeal Membrane Oxygenation in Adult Burn Patients
Authors: Chou Nai‐Kuan , Chen Yih‐Sharng , Ko Wen‐Je , Huang Shu‐Chien , Chao Anne , Jan Gwo‐Jen , Lin Fang‐Yue , Wang Shoei‐Shen , Chu Shu‐Hsun
Published: March 2003

Abstract: Adult respiratory distress syndrome (ARDS) has been the major cause of mortality in burn injury. The authors reported the experience of using extracorporeal membrane oxygenation (ECMO) to treat adult burn patient with ARDS. Three patients with burn or electric injury, around 48.9% of body surface area over second‐degree burns, developed ARDS after resuscitation. All had positive blood culture and depended on a ventilator more than 5 days before ECMO. Venovenous (VV) ECMO was started at the beginning of severe respiratory failure with an oxygen index of 61.6 ± 15.5 cm H2O/mm Hg (≧40 cm H2O/mm Hg), partial arterial oxygen tension to inspired oxygen fraction (Pao2/Fio2) of 46.1 ± 7.0 mm Hg (≤200 mm Hg), positive end expiratory pressure (PEEP) of 15.7 ± 1.6 cm H2O (≧10 cm H2O), alveolar‐arterial difference in oxygen concentration (A‐a Do2) of 618.9 ± 19.3 mm Hg (≧300 mm Hg), and lung compliance of 17.3 ± 4.6 ml/cm H2O (≤30 ml/cm H2O). The VV type had to be converted to the newly designed veno‐venoarterial (V‐VA) ECMO due to the myocardial dysfunction. Two of three patients survived. The duration of ECMO was 160.2 ± 51.1 h. Two patients received debridement of escar during ECMO support and desmopressin infusion, and no increased bleeding or coagulopathy was found. The respiratory parameters were significantly improved after ECMO, especially in the survivors. ECMO is also suitable for ARDS in adult burn injury.
Percutaneous Extracorporeal Life Support for Treatment of Fatal Mechanical Complications Associated with Acute Myocardial Infarction
Authors: Fujimoto Koichi , Kawahito Koji , Yamaguchi Atsushi , Sakuragawa Hiroshi , Tsuboi Junichi , Yuri Koichi , Tanaka Masashi , Endo Hidehito , Adachi Hideo , Ino Takashi
Published: March 2003

Abstract: Mechanical complications of acute myocardial infarction (AMI), such as free wall rupture, ventricular septal perforation (VSP), and mitral regurgitation due to papillary muscle rupture, are associated with high mortality rates. These complications result in extreme deterioration and increased risk of death in patients who do not receive timely resuscitation and surgical treatment. We studied the effectiveness of percutaneous extracorporeal life support (ECLS) for fatal mechanical AMI complications. Nine patients (7 men and 2 women, mean age 69 ± 6 years) who suffered circulatory collapse refractory to conventional resuscitation were treated with ECLS. Circulatory collapse was caused by free wall rupture in 4 patients, VSP in 4, and mitral regurgitation due to papillary muscle rupture in 1. All patients were successfully resuscitated by ECLS and underwent surgical repair with conventional cardiopulmonary bypass. Eight patients required ECLS after surgery. Four of the 9 patients (2 with free wall rupture, 1 with VSP, and 1 with papillary muscle rupture) were successfully weaned from ECLS and were discharged. Three of the 4 survivors had no major complications, but the remaining survivor suffered neurological deficit. Four patients died while on devices. The duration of ECLS was from 13 to 167 h (mean 76 ± 57 h) with a maximum bypass flow of 2.0 to 3.9 L/min (mean 2.9 ± 0.6 L/min). There were no device‐related complications during the support period. Total weaning rate was 56% (5/9), and survival was 44% (4/9). We conclude that ECLS can provide appropriate circulatory support during resuscitation and subsequent postoperative circulatory support for cardiovascular collapse associated with AMI complications.
Recent Progress on the Vibrating Flow Pump as a Totally Implantable Ventricular Assist Device
Authors: Yambe Tomoyuki , Kobayashi Shin‐ichi , Yoshizawa Makoto , Tanaka Akira , Matsuki Hidetoshi , Sato Fumihiro , Tabayashi Kouichi , Nitta Shin‐ichi
Published: March 2003

Abstract: This study describes the present state of progress in the development of the vibrating flow pump (VFP) ventricular assist system. We have proceeded with development aiming at a totally implantable ventricular assist system with smaller size and lighter weight appropriate for Asians like the Japanese by increasing the drive frequency. An actuator is important for the development of the miniature sized and lightweight artificial heart. We applied a linear motor for the mechanical part at first. The step motor was applied after that. This form may be best if we want the lightweight small sized motor for an actuator. The cross slider form is applied at present. It succeeded in the miniaturization compared with the linear motor. In the VFP‐type ventricular assist system, the blood contact parts are a central vibration tube with inflow and outflow chambers. We designed round diaphragms to prevent thrombus formation. In addition, we developed an energy transmission system for total implantation. The VFP creates a high frequency oscillated blood flow. It has a unique flow pattern. Brain blood flow increased although the total flow of the circulation did not change in the frequency of 25 to 30 Hz. The quantitative evaluation of the autonomic nerve function during the left heart assistance with an oscillated blood flow was carried out by spectral analysis. Some influences on an autonomic nerve were observed by the VFP left heart assistance. We will continue development research with the aim of clinical application.
Application of Indirect Flow Rate Measurement Using Motor Driving Signals to a Centrifugal Blood Pump with an Integrated Motor
Authors: Tsukiya Tomonori , Taenaka Yoshiyuki , Nishinaka Tomohiro , Oshikawa Mitsuo , Ohnishi Hiroyuki , Tatsumi Eisuke , Takano Hisateru , Konishi Yoshiaki , Ito Kazuyuki , Shimada Mitsumasa
Published: March 2003

Abstract: The method of measuring the flow rate of a centrifugal blood pump from the input electric power, which will be indispensable for the long‐term use of such devices, was developed and was applied to the direct‐driven centrifugal blood pump that has been developed by our research group. The accuracy was evaluated in a chronic animal experiment using an adult goat. The results demonstrated that this method carries the sufficient potential of the instantaneous monitoring method, but errors due to electromagnetic and mechanical losses were not determined always precisely. The detection of adverse phenomena such as the obstruction of the inlet cannula was also possible from the estimated value of the flow rate and its waveform pattern.
Motor Current Waveforms as an Index for Evaluation of Native Cardiac Function During Left Ventricular Support with a Centrifugal Blood Pump
Authors: Kikugawa Daiki
Published: March 2003

Abstract: Control of ventricular assist devices (VADs) for native heart preservation should be attempted, and it could be one strategy for dealing with the shortage of donors in the future. In the application of a nonpulsatile blood pump for ventricular assistance from its apex to the aorta, the bypass flow and hence motor current of the pumps change in response to the ventricular pressure change. Utilizing these intrinsic characteristics of the continuous flow pumps, this study investigated whether or not motor current could be used as an index for continuous monitoring of native cardiac function. In Study 1, a centrifugal blood pump (CFP) VAD was installed between the apex and descending aorta of a mock circulatory loop. In this model, a baseline with a preload of 10 mm Hg, afterload of 40 mm Hg, and left ventricular (LV) systolic pressure of 40 mm Hg was used. The pump rpm were fixed at 1,300, 1,500, and 1,700, and LV systolic pressure was increased up to 140 mm Hg by a step of 20 mm Hg while observing the changes in LV pressure, motor current, pump flow, and aortic pressure. In Study 2, in vivo experiments were performed using 5 sheep. A left heart bypass model was created using a centrifugal pump from the ventricular apex to the descending aorta. The LV pressure was varied through administration of dopamine while observing the changes in LV pressure, pump flow, motor current, and aortic pressure at 1,500 and 1,700 rpm. An excellent correlation was observed both in vitro and in vivo studies in the relationship between motor current and LV pressure. In Study 1, the correlation coefficients were 0.77, 0.92, and 0.99 for 1,300, 1,500, and 1,700 rpm, respectively. In Study 2, they were 0.90 (Animal 1), 0.82 (Animal 2), 0.89 (Animal 3), 0.93 (Animal 4), and 0.70 (Animal 5) respectively for 1,500 rpm, and 0.94 (Animal 2), 0.85 (Animal 3), 0.94 (Animal 4), and 0.89 (Animal 5) respectively, for 1,700 rpm. The relationship between motor current and pump flow and LV pressure showed an unstable correlation in an in vivo study. These results suggest that motor current amplitude monitoring could be useful as an index for the control of VADs for native heart preservation.
Investigation of the Flow Performance of a Nutating Blood Pump by Computational Fluid Dynamics
Authors: Sartori‐Montecroce Oliver , Goubergrits Leonid , Affeld Klaus
Published: March 2003

Abstract: In centrifugal blood pumps, blood is moved into a circular path with the help of an impeller. In a nutating pump, the nutating body takes over the role of the impeller. Since the nutating body itself does not rotate, this pump needs no seal, no blood contacting, and no magnetic bearings. To examine the suitability of the nutating pump principle for mechanical heart assist, the flow performance of different nutating pump models was investigated by computational fluid dynamics. The geometrical parameters of the pump were varied and flow‐pressure curves were calculated for 12 models at different rotation frequencies. All models showed satisfactory flow‐pressure curves. One model was computed minutely at 1 flow configuration to examine shear stresses within the fluid. A flow of 5 L/min and a frequency of 3,300 rotations per min (rpm) resulted in a differential pressure of 85 mm Hg. The maximum shear stress in the fluid at this flow was estimated to be 193 Pa which is considered to be an acceptable value for a blood pump.
Comparison of Two Filter Combinations for Low‐Density Lipoprotein Apheresis by Membrane Differential Filtration: A Prospective Crossover Controlled Clinical Study
Authors: Matic Goran , Kohlschein Peter , Wallstab Uwe , Tiess Michael , Winkler Roland , Prophet Heinrich , Ramlow Wolfgang , Schuff‐Werner Peter
Published: March 2003

Abstract: Membrane differential filtration is an accepted procedure for the extracorporeal removal of low‐density lipoprotein (LDL). Reduction rates largely depend on the nature of the membranes and are ideally evaluated in a crossover study design. Four patients who had been treated by LDL apheresis for at least 6 months were included. Six consecutive weekly sessions (40 ml plasma/kg body weight) were scheduled per system (Plasmacure PS06/Evaflux Eval 5A [Kuraray] versus Plasmaflo OP05W/Cascadeflo AC1770 [Asahi]). Laboratory measurements indicated reductions of plasma concentrations for fibrinogen (37%[Kuraray] versus 44%[Asahi]), IgG (15% versus 20%), IgA (24% versus 28%), IgM (63% versus 53%), and total protein (11% versus 16%). Total cholesterol was eliminated by 52% versus 49%, LDL by 67% versus 66%, triglycerides by 56% versus 41%, and high‐density lipoprotein by 10% versus 20%. Three therapies employing the Asahi filter combination were terminated prematurely due to saturation of the plasma fractionator. In conclusion, despite similar physical properties, the membranes differ significantly concerning selectivity and sensitivity to saturation.
An Infection‐Preventing Bilayered Collagen Membrane Containing Antibiotic‐Loaded Hyaluronan Microparticles: Physical and Biological Properties
Authors: Lee Jong‐Eun , Park Jong‐Chul , Lee Kwang Hoon , Oh Sang Ho , Kim Joong‐Gon , Suh Hwal
Published: March 2003

Abstract: An infection‐preventing bilayered membrane consisting of a dense and porous collagen membrane has been developed. The membrane was fabricated using a combined freeze‐drying/air‐drying method. Hyaluronan (HA) microparticles containing silver sulfadiazine (AgSD) were fabricated by gelling an HA solution with calcium chloride and were incorporated into collagen layers to allow the sustained release of AgSD. In vitro biodegradability of the membrane and the release of AgSD from the membrane could be controlled by cross‐linking the membrane with ultraviolet (UV) irradiation. In a cytotoxicity test, cellular damage was minimized by the sustained release of AgSD from dressings. The antibacterial capacity of the material against Pseudomonas aeruginosa was investigated using the Bauer‐Kirby disk diffusion test, and bacterial growth was found to be inhibited for 4 days. In vivo tests showed that the bilayered membrane was associated with greater tissue regeneration than a polymeric membrane and with no infection‐related biological signs.