bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Avoidance of Air Contact Necessary for the In Vitro Evaluation of Thrombogenicity in Mechanical Circulatory Assist Devices?
Authors: Kim Won Gon , Na Myung‐Hoon , Kim Joo Hyun
Published: March 2003

Abstract: An effective in vitro protocol for the investigation of thrombogenicity can provide many advantages in the development of mechanical circulatory assist devices. Strict avoidance of air contact with blood recently was proposed for reliable in vitro evaluation. This study was performed to confirm the necessity of avoidance of air contact for the in vitro test of thrombogenicity in a rotary pump. Two sets of mock circuits with the same rotary blood pumps, reservoirs, and connecting tubes were made. In one system, blood came in contact with air while the other did not. The test blood was heparinized at the dose of 1 IU per 1 ml of blood. The tests were terminated at an activated coagulation time of 1.5 times the control value. The levels of hematocrit, platelet, factors VIII and XII, fibrinogen, thromboxane B2, and plasma‐free hemoglobin were measured during the procedures. After the experiments, the thrombi formed were observed, measured, and compared with those formed in in vivo circumstances. The tests were repeated 12 times. There were no statistically significant differences between the 2 groups in hematologic parameters and the amounts of thrombi formed. The thrombi observed in both groups showed the same pathologic findings as those formed in vivo with the exception of intermittent multiple air bubbles found in thrombi of the air‐contact group. In conclusion, the effect of air contact in the in vitro investigation of thrombogenicity was negligible while the proposed in vitro test models of thrombogenesis in the mechanical circulatory assist device proved to be reliable.
Artificial Sensorimotor Integration in Spinal Cord Injured Subjects Through Neuromuscular and Electrotactile Stimulation
Authors: De Castro Maria Claudia Ferrari , Cliquet, Jr. Alberto
Published: March 2003

Abstract: Spinal cord injured (SCI) subjects lack sensorimotor functions. Neuromuscular electrical stimulation (NMES) systems have been used to artificially restore motor functions, but without proprioceptive feedback, SCI subjects can control NMES systems only when they can see their limbs. In a gait restoration system, the subject looks down to the ground to be aware of where his foot is while in a grasping activity, maximum grip strength is employed regardless of the force that is required to perform tasks. This report focuses on artificial sensorimotor integration. Multichannel stimulation was used to restore motor functions while encoded tactile sensation (moving fused phantom images) relating to artificially generated movements was provided by electrotactile stimulation during walking and grasping activities. The results showed that the sensorimotor integration attained yielded both the recognition of artificial grasp force patterns and a technique to be used by paraplegics allowing spatial awareness of their limb while walking.
Right Ventricular Assist System Feedback Flow Control Parameter for a Rotary Blood Pump
Authors: Yoshikawa Masaharu , Nakata Kin‐ichi , Nonaka Kenji , Linneweber Joerg , Kawahito Shinji , Takano Tamaki , Shulte‐Eistrup Sebastian , Maeda Tomohiro , Glueck Julia , Schima Heinrich , Wolner Ernst , Nosé Yukihiko
Published: March 2003

Abstract: At least 25–30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different pump flows were investigated: Group 1 low assist (<3.5 L/min) and Group 2 high assist (>3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate.
Numerical Analysis of Blood Flow in the Clearance Regions of a Continuous Flow Artificial Heart Pump
Authors: Anderson Jay , Wood Houston G. , Allaire Paul E. , Olsen Don B.
Published: March 2003

Abstract: The CFVAD3 is the third prototype of a continuous flow ventricular assist device being developed for implantation in humans. The pump consists of a fully shrouded 4‐blade impeller supported by magnetic bearings. On either side of this suspended rotating impeller is a small clearance region through which the blood flows. The spacing and geometry of these clearance regions are very important to the successful operation of this blood pump. Computational fluid dynamics (CFD) solutions for this flow were obtained using TascFlow, a software package available from AEA Technology, U.K. Flow in these clearance regions was studied parametrically by varying the size of the clearance, the blood flow rate into the pump, and the rotational speed of the pump. The numerical solutions yield the direction and magnitude of the flow and the dynamic pressure. Experimentally measured pump flow rates are compared to the numerical study. The results of the study provide guidance for improving pump efficiency. It is determined that current clearances can be significantly reduced to improve pump efficiency without negative impacts.
Using One Rotary Blood Pump to Produce Separate Pulsatile Circulations in the Upper and Lower Halves of the Body
Authors: Isoyama Takashi , Abe Yusuke , Chinzei Tsuneo , Mochizuki Shuichi , Karita Tatsuro , Saito Itsuro , Ono Toshiya , Kouno Akimasa , Baba Kazunori , Imachi Kou
Published: March 2003

Abstract: Separate systemic circulations with pulsatile flow were obtained using 1 rotary blood pump as a left ventricular assist device. The outlet of the pump was divided into 2 conduits, 1 connected to the upper half of the body and the other connected to the lower half. An electric actuator that clamped the 2 outlet conduits alternately provided pulsatile flows. An in vitro experiment showed that the pulsatility phases of the upper and lower halves of the body were complementary with pulsatile flow, and an in vivo experiment showed that controlled flow distributions of continuous flows could be obtained.
Hemodynamic Performance of Small‐Size Bileaflet Valves: Pressure Drop and Laser Doppler Anemometry Study Comparison of Three Prostheses
Authors: Grigioni Mauro , Daniele Carla , D'avenio Giuseppe , Barbaro Vincenzo
Published: March 2003

Abstract: Laser Doppler anemometry (LDA) is a single‐point technique which is unparalleled to detect accurately the local properties of the velocity field in a turbulent flow, such as that generated by a prosthetic heart valve (PHV). We propose a correlation between the structure of the flow field in three 19 mm bileaflet PHVs (Sorin Bicarbon, St. Jude Standard, St. Jude HP), investigated at peak systole (6 L/min cardiac output [CO]) with LDA, in kinematic and geometric similarity, and the global parameter of transvalvular pressure drop measured in both steady and pulsatile conditions. The pressure transducers of the same apparatus were used to characterize pressure drops at different flow rates whereas the steady‐flow case was studied with a highly accurate tester built in our laboratory. The 2 St. Jude models rank according to their internal orifice diameter (ID) with the standard model (with a smaller ID) providing higher pressure drops for each flow rate. Sorin Bicarbon, due to its leaflet geometry, generates a more complex flow field with respect to the 2 St. Jude flat‐leaflet models and shows improved hemodynamical behavior in pulsatile conditions with respect to the stationary case due to differences in pressure recovery. This study can provide insights into a PHV's local flow structure and global hemodynamical parameters.
Safe and Efficient Gene Transfer into Porcine Hepatocytes Using Sendai Virus‐Cationic Liposomes for Bioartificial Liver Support
Authors: Kawashita Yujo , Ohtsuru Akira , Fujioka Hikaru , Kamohara Yukio , Kawazoe Yasushi , Sugiyama Nozomu , Eguchi Susumu , Kuroda Hiroaki , Furui Junichiro , Yamashita Shunichi , Kaneda Yasufumi , Kanematsu Takashi
Published: March 2003

Abstract: Establishment of a bioartificial liver support system using genetically modified hepatocytes is a potential approach to improve the treatment of severe liver failure. We describe the development of an efficient ex vivo method of gene transfer into a large number of porcine hepatocytes using hemagglutinating virus of Japan (HVJ)‐liposome. The transfection efficiency of HVJ‐liposome into isolated porcine hepatocytes attached to microcarrier beads was evaluated by β‐galactosidase (β‐gal) staining, fluorescence activated cell sorting analysis for β‐gal and luciferase assay, respectively. To examine the function and cellular damage of transduced hepatocytes, we used enzyme‐linked immunosorbent assay for porcine albumin synthesis, lidocaine clearance test (P‐450 activity), aspartate aminotransferase, and lactic dehydrogenase release assays. The optimal conditions for gene transfer into the beads‐attached hepatocytes using HVJ‐liposome included 4 μg of deoxyribonucleic acid with 200 μg of lipid/2 × 105 cells and exposure duration of 90 min. Under these conditions, β‐gal and luciferase genes were transduced to 2.5 × 108 isolated porcine hepatocytes following attachment to the beads. Positive β‐gal staining was observed in more than 30% of the beads‐attached hepatocytes. The gene transfer activity of HVJ‐liposome method determined by luciferase activities was about 100‐fold of that of the lipofection method. Transfected porcine hepatocytes remained functional without any significant cell damage. Our results demonstrated that HVJ‐liposome mediated gene transfer into microcarrier‐attached porcine hepatocytes is an efficient and nontoxic method suitable for a bioartificial liver support sytem.
Changes in Patterns of Left Ventricular Hypertrophy After Aortic Valve Replacement for Aortic Stenosis and Regurgitation with St. Jude Medical Cardiac Valves
Authors: Murakami Taiji , Kikugawa Daiki , Endou Kouichi , Fukuhiro Yoshiaki , Ishida Atsuhisa , Morita Ichiro , Masaki Hisao , Inada Hiroshi , Fujiwara Takashi
Published: March 2003

Abstract: In this study, we analyzed the extent and pattern of regression of left ventricular (LV) hypertrophy after aortic valve replacement in patients with aortic stenosis (AS) and compared the results with those of another group of patients with aortic regurgitation (AR). Seventy patients who underwent isolated aortic valve replacement were divided into 2 groups. Group 1 was comprised of 29 patients who underwent aortic valve replacement for aortic stenosis, and Group 2 of 41 patients who underwent aortic valve replacement for aortic regurgitation. A third group of 10 healthy subjects served as a healthy control group. Echocardiographic studies were done before the operation and 5 years postoperatively. At follow‐up, a significant reduction in the left ventricular mass was found in both groups, but it remained significantly greater than in the healthy control group. The ratio of LV wall thickness to radius (th/r) in Group 1 decreased significantly, and at follow‐up it was within the normal value. In Group 2, the th/r ratio increased, and at follow‐up it was within the normal value. After aortic valve replacement, the wall thickness remained significantly greater than normal for patients with AS, and the chamber radius remained significantly greater than normal for patients with AR. For these reasons, LV hypertrophy still existed in both groups at postoperative follow‐up. The actuarial survival rate was 85.3% at 16 years for Group 1 and 83.4% at 18 years for Group 2. There was no significant difference in the long‐term survival rates between the 2 groups. Actuarial freedom from valve‐related events was 91.9% at 16 years for Group 1 and 82% at 18 years for Group 2. There was no significant difference in the valve‐related event free curves between groups. After 5 years of follow‐up, th/r reached normal for both groups, indicating remodeling of the LV geometry after aortic valve replacement.
Intestinal Tissue Oxygenation and Tumor Necrosis Factor‐α Release During Systemic Blood Flow Changes in Pigs with Left Ventricular Assist Devices
Authors: Uozaki Yasuhiro , Dihmis Walid C. , Yamauchi Hidetoshi , Moczar Madeleine , Miyama Masatoshi , Pasteau Fabien , Tixier Denis , Bambang Sektiari L. , Loisance Daniel Y.
Published: March 2003

Abstract: We previously demonstrated that tumor necrosis factor‐α (TNF‐α) increased following a reduction in systemic blood flow to 60% or less of the original cardiac output using a left ventricular assist device (LVAD). The aim of this study was to investigate the effect of reducing systemic blood flow on tissue oxygenation in the gastrointestinal tract (GIT) and the consequences of this on TNF‐α release. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF‐α of the superior mesenteric vein was measured at baseline and during systemic blood flow changes. Simultaneously, pH, lactate, oxygen delivery index (Do2I), oxygen consumption index (Vo2I), and oxygen extraction (O2ER) in the GIT were measured. The pH decreased and the lactate level increased significantly (p < 0.05) at a systemic blood flow of 50% or less. The Vo2I was positively correlated with Do2I. The O2ER increased significantly (p < 0.05) with reductions in systemic blood flow to 30% or less. There was a significant (p < 0.01) correlation between TNF‐α and O2ER at levels higher than 55%. These data demonstrate that the GIT oxygenation is inadequate with a reduction in systemic blood flow to 50% and that GIT oxygenation becomes critical at a reduction of 30%. During LVAD weaning, careful attention must be given to the GIT. The pH and lactate may be good markers of the adequacy of tissue oxygenation in the GIT.
Effect of Variation in Systemic Blood Flow on Plasma TNF‐α in a Pig Model with Left Ventricular Assist Device
Authors: Uozaki Yasuhiro , Dihmis Walid C. , Yamauchi Hidetoshi , Moczar Madeleine , Miyama Masatoshi , Pasteau Fabien , Tixier Denis , Bambang Sektiari L. , Loisance Daniel Y.
Published: March 2003

Abstract: Tumor necrosis factor‐α (TNF‐α) release has been implicated in a sepsis‐like syndrome following cardiopulmonary bypass (CPB). This also may be important in patients who have had a left ventricular assist device (LVAD) implanted. This report investigates the effect of reducing systemic blood flow on hemodynamic response, mixed venous oxygen saturation (Svo2), and the release of TNF‐α. LVADs were implanted in 9 pigs. The aorta was clamped, and thus the LVAD flow represented the entire systemic blood flow. Plasma TNF‐α in the femoral artery (FA) and superior mesenteric vein (SMV) was measured at baseline and following systemic blood flow changes. Simultaneously, hemodynamic parameters and oxygen saturation in the pulmonary artery (Svo2) were measured. Following reductions in systemic blood flow, plasma TNF‐α increased gradually to a maximum level at a systemic blood flow of 20%. There was no significant difference between TNF‐α levels in the SMV and the FA. There was a significant (p < 0.05) correlation between cardiac index, stroke volume index, and TNF‐α. The Svo2 decreased significantly (p < 0.05) at a systemic blood flow of 30 and 20%. A rise in TNF‐α occurred when the Svo2 was less than 75%. The data demonstrate that a reduction in systemic blood flow causes an increase in plasma TNF‐α. This can lead to the development of a sepsis‐like syndrome in a group of patients who already are hemodynamically compromised. While weaning short‐term LVAD support, rapid diminution of the cardiac output and the pump flow must be avoided.
Indications for Rotary Blood Pumps in Clinical Practice
Authors: Meyns B.
Published: March 2003

Abstract: To understand the needs and requirements in the development of rotary blood pumps, we have to consider the current use and limitations of blood pumps in cardiac surgery. There are 5 different fields of indications for blood pumps in cardiac surgery. First, there is the possibility to use rotary blood pumps in the cardiopulmonary bypass system. Second, miniaturized rotary blood pumps can be used to support beating heart surgery. Third, we expect a growing use of rotary blood pumps in short‐term ventricular support. The same applies to the field of chronic cardiac failure and long‐term myocardial support. Finally, miniaturized rotary blood pumps can be used to support the ventricle during myocardial infarction. Rotary blood pumps are expected, based on their features, to progress in all these indications.
Computational Fluid Dynamics Performance Prediction for the Hydrodynamic Bearings of the VentrAssist Rotary Blood Pump
Authors: Bertram Christopher D. , Qian Yi , Reizes John A.
Published: March 2003

Abstract: Finite‐volume computations are described for laminar flow in the hydrodynamic bearings supporting 2 different versions of the impeller of the VentrAssist rotary pump. Pressure boundary conditions are taken from prior computations of turbulent flow in the whole pump with frictionless sliding of the impeller on the inside of the pump body. By investigating various impeller positions, the true ride height is determined. Net lift and combined drag from all 8 bearings of the 4‐bladed impeller are compared with predictions based on 2‐D theory. The computations also reveal the extent of net force and moment acting to move the impeller away from its nominal axis of rotation.
Blood Pumps: Technologies and Markets in Transformation
Authors: Anderson Dallas W.
Published: March 2003

Abstract: The heart failure industry or sector of blood pump technologies comprised of scientists, medicine, and business has inadequate attention from the financial community due to the perception of unmet market potential and regulatory hurdles. There are more than 20 mechanical circulatory support technologies currently in some stage of development. The application is defined initially for emerging technologies as bridge‐to‐transplant whereas more mature devices have focused on bridge‐to‐recovery and alternative‐to‐transplant. Regulatory hurdles and financing resources have dictated this initial application strategy. Whether a technology has valves, bearings, is magnetically suspended, acts as a pressure cuff, and so on, the future will belong in large part to those technologies that are less expensive, have improved ergonomics, are simpler in surgical application, and can demonstrate efficacy levels that are an improvement over today's approved devices. Today's devices have provided a valuable platform for the emerging technologies. However, there has been little market expansion over these past years, relative to the potential market. The cardiologist is the patient's gatekeeper, and drugs appear to be the therapy of choice as options are considered. Technologies without a business model will have a difficult time attracting much needed funding, the result being protracted development times or project termination. MicroMed has modified its ventricular assist device (VAD) focus, with a broader look at treating the heart failure patient. MicroMed recently entered into an agreement with Chrysalis Biotechnology, Inc., Galveston, TX, covering a synthetic peptide technology (Chrysalin) that when injected into tissue has demonstrated an angiogenic effect without the concerns inherent in recombinant angiogenic/growth factors. We believe a combination therapy of the DeBakey VAD‐synthetic peptide could provide sufficient revascularization for bridge‐to‐recovery or as an alternative‐to‐transplant in certain patients.
Development Status of Terumo Implantable Left Ventricular Assist System
Authors: Nojiri Chisato , Kijima Toshihiko , Maekawa Jun , Horiuchi Kunio , Kido Takayuki , Sugiyama Tomoko , Mori Takehisa , Sugiura Naoya , Asada Takehiko , Umemura Wataru , Ozaki Takayoshi , Suzuki Minoru , Akamatsu Teruaki , Westaby Stephen , Katsumata Takahiro , Saito Satoshi
Published: March 2003

Abstract: We have been developing an implantable left ventricular assist system (T‐ILVAS) featuring a magnetically suspended centrifugal pump (MSCP) since 1995. In vitro and in vivo studies using a prototype MSCP composed of a polycarbonate housing and impeller (196 ml) have demonstrated long‐term durability and excellent blood compatibility for up to 864 days, and excellent stability of the magnetic bearing of the MSCP. These preliminary results strongly suggested that the magnetic bearing of the MSCP is reliable and is a most feasible mechanism for a long‐term circulatory assist device. We have recently devised a clinical version pump made of titanium (180 ml) with a new position sensor mechanism and a wearable controller with batteries. Cadaver fit study confirmed that the Type IV pump could be implanted in a small patient with a body surface area as small as 1.3. The in vitro performance tests of the Type IV pump demonstrated excellent hydrodynamic performances with an acceptable hemolysis rate. New position sensors for the titanium housing showed more uniform sensor outputs of a magnetic bearing than in the prototype polycarbonate pump. The Type IV pump then was evaluated in vivo in 6 sheep at the Oxford Heart Centre. Four sheep were electively sacrificed at 3 months and were allowed to survive for more than 6 months for long‐term evaluation. In this particular series of experiments, no anticoagulant/antiplatelet regimen was utilized except for a bolus dose of heparin during surgery. There was a left ventricular mural thrombi around the inflow cannula in 1 sheep. Otherwise, there was no mechanical failure nor sign of thromboembolism throughout the study.
Relation Between Echinocytosis and Erythrocyte Calcium Content in Hemodialyzed Uremic Patients
Authors: Agroyannis B. , Kopelias I. , Fourtounas C. , Paraskevopoulos A. , Tzanatos H. , Dalamangas A. , Mallas E.
Published: March 2003

Abstract: A rise in intracellular calcium concentration in erythrocytes has multiple effects on these cells. The purpose of this study was to determine the changes of calcium content in red blood cells (RBCs) and of echinocyte percentages in uremic patients during hemodialysis sessions. In 30 uremic patients under hemodialysis, the calcium content of RBCs and echinocyte percentages were determined in 3 blood samples collected at 0 min hemodialysis (prehemodialysis), 45 min hemodialysis, and 240 min hemodialysis (end hemodialysis) for a 4 h hemodialysis session. Calcium content of RBCs and echinocytes were also determined in 22 normal subjects (controls). The findings of the present study were that the mean values (±SD) of calcium content of RBCs in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 min hemodialysis were 2.00 ± 1.0, 2.66 ± 0.87, and 1.62 ± 0.66 μg/ml respectively and 0.65 ± 0.07 μg/ml in controls. These values show that the calcium content of RBCs in uremic patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis was significantly higher than in controls (p < 0.0001), and that RBC calcium content at 45 min hemodialysis was significantly higher in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001), while that at 240 min hemodialysis was significantly lower than at 0 min hemodialysis (p < 0.05). The mean values (±SD) of echinocyte percentages in patients at 0 min hemodialysis, 45 min hemodialysis, and 240 hemodialysis were 11.93 ± 6.18, 17.23 ± 4.1, and 7.96 ± 5.67% respectively, and in controls ranged from 0 to 1%. The values in uremic patients show a transient increase of echinocyte percentages at 45 min hemodialysis, which is significant in comparison to that at 0 min hemodialysis (p < 0.001) and to that at 240 min hemodialysis (p < 0.0001). Echinocyte percentages at 240 min hemodialysis were significantly lower to those at 0 min hemodialysis (p < 0.001). Correlation between calcium content of erythrocytes and echinocyte percentages shows a significantly positive relationship at 45 min hemodialysis (r = 0.368, p < 0.05) but no significant relationship at 0 min hemodialysis and 240 min hemodialysis. In conclusion, uremic patients under hemodialysis present with high calcium content in erythrocytes and abnormal erythrocytes like echinocytes. A rapid and transient increase of erythrocyte calcium is also accompanied by transient elevation of echinocytes in the first hour of hemodialysis (45 min hemodialysis), which returns after hemodialysis to lower than prehemodialysis levels.
Amplification of Engrafted Hepatocytes by Preparative Manipulation of the Host Liver
Authors: Guha Chandan , Deb Niloy J. , Sappal Baljit S. , Ghosh Siddhartha S. , Roy‐Chowdhury Namita , Roy‐Chowdhury Jayanta
Published: March 2003

Abstract: Scarcity of donor livers is a major obstacle to the general application of hepatocytes for the development of bioartificial liver assist devices as well as intracorporeal engraftment of hepatocytes for the treatment of inherited metabolic diseases. The number of hepatocytes that can be transplanted into the liver safely in a single sitting also limits the utility of this procedure. These limitations could be addressed by providing preferential proliferative advantage to the transplanted cells. Studies using transgenic mouse recipients or donors have indicated that massive repopulation of the host liver by engrafted hepatocytes requires that the transplanted cells are subjected to a proliferative stimulus to which the host hepatocytes cannot respond. Prevention of host hepatocyte proliferation has been achieved by treatment with a plant alkaloid, retrorsine. Because retrorsine is carcinogenic, we have evaluated preparative irradiation for this purpose. The proliferative stimulus may consist of the loss of hepatic mass (e.g., partial hepatectomy, reperfusion injury or induction of Fas‐mediated apoptosis by gene transfer) or administration of stimulants of hepatocellular mitosis (e.g., growth factors or thyroid hormone). Potential applications of these preparative manipulations of the host liver include the treatment of inherited metabolic disorders by transplantation of allogeneic hepatocytes, hepatocyte‐mediated ex vivo gene therapy, rescuing liver cancer patients from radiation‐induced liver damage, and expansion of human hepatocytes in animal livers.
Mechanical Bridge with Extracorporeal Membrane Oxygenation and Ventricular Assist Device to Heart Transplantation
Authors: Wang Shoei‐Shen , Ko Wen‐Je , Chen Yih‐Sharng , Hsu Ron‐Bin , Chou Nai‐Kuan , Chu Shu‐Hsun
Published: March 2003

Abstract: The aim of this study was to evaluate the effect of double bridges with extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs) in clinical heart transplantation. Between May 1994 and October 2000, 134 patients underwent heart transplantation at the National Taiwan University Hospital. Ten patients received ECMO or VAD support as bridges to transplantation. The ages ranged from 3 to 63 years. The indications included cardiac arrest under cardiopulmonary resuscitation in 2 and profound cardiogenic shock refractory to conventional therapy in 8 patients. Usually ECMO was first set up as rescue therapy. If ECMO could not be weaned off after short‐term (usually 1 week) support, suitable VADs (HeartMate or Thoratec VAD) were implanted for medium‐term or long‐term support. Five patients received ECMO support as emergency rescue for 2 to 9 days, and then moved to Thoratec VAD for 8, 49, and 55 days, respectively, or centrifugal VAD for 31 days, or HeartMate VAD for 224 days. They all survived. The survival rate of double bridges with ECMO and VAD was 100%. In postcardiotomy cardiogenic shock, circulatory collapse from acute myocardial infarction or myocarditis, ECMO is the device of choice for short‐term support. If heart transplantation is indicated, VADs should replace ECMO for their superiority as a bridge to heart transplantation. Our preliminary data of double bridges with ECMO and VAD revealed good results and were reliable and effective bridges to transplantation.
Refractive Tunnel Keratoplasty with Synthetic Implants Modified by a Gas‐Discharge Plasma
Authors: Shusterov Y.A. , Bragin V.E. , Bykanov A.N. , Eliseeva E.V.
Published: March 2003

Abstract: Various methods of refractive interlamellar tunnel keratoplasty with synthetic implants modified by low‐temperature gas‐discharge plasma were used for correction of myopia and myopic astigmatism. Experiments carried out with laboratory rabbits revealed that pretreatment of hydrogel, silicon, and polymethylmethacrylate by gas‐discharge plasma enhances the tolerance of corneal stroma to these synthetic materials. Clinical studies with hydrogel have shown that gas‐discharge plasma treatment of traditional polymer materials is a promising method for achieving improved biocompatibility of synthetic materials to corneal stroma. Forty‐four clinical tunnel keratoplasties have been conducted on humans with gas‐discharge‐plasma‐treated hydrogel. The patients had a high degree of myopia (from 7.0 to 28.0 D) and myopic astigmatism (within the range of 5.0 to11.0 D). Surgical methods were similar to those developed during the experimental stage of work. The patients were followed postoperatively for up to 8 years. According to these observations, circular tunnel keratoplasty with synthetic implants reduced spherical myopia up to 20.0 D. Methods for correcting of both simple and complex myopic types of astigmatism have been developed. Arc‐type sectoral tunnel keratoplasty and elliptical tunnel keratoplasty allowed correction of myopic astigmatism up to 11.0 D.
Hemodynamic Exercise Response in Calves with an Implantable Biventricular Centrifugal Blood Pump
Authors: Linneweber Jörg , Nonaka Kenji , Takano Tamaki , Kawahito Shinji , Schulte‐Eistrup Sebastian , Motomura Tadashi , Ichikawa Seiji , Mikami Minoru , Stevens Shelly , Schima Heinrich , Wolner Ernst , Nosé Yukihiko
Published: March 2003

Abstract: An implantable biventricular assist device (BVAD) has been developed at Baylor College of Medicine using 2 centrifugal blood pumps. The aim of this study was to investigate the exercise‐reflex response during nonpulsatile biventricular assistance and to evaluate to which degree the autoregulation of the system would accommodate the changed hemodynamic situation during physical exercise. The Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half‐Dexter) in a biventricular bypass fashion with native heart remaining. Allowing a 10 day convalescence, 2 animals were subjected to incremental exercise tests. The speed of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with increments of 0.2 mph every 3 min. During the exercise the pump flows were maintained at a fixed rate (6.93 ± 0.01 L/min for the left ventricular assist device and 5.36 ± 1.44 L/min for the right ventricular assist device). Hemodynamic parameters and pump performance were recorded continuously. The cardiac output (CO) and heart rate (HR) increased significantly during the exercise. CO increased from 11.1 ± 0.3 to 13.1 ± 0.4 L/min, and HR increased from 99 ± 7.1 to 114 ± 2.8 bpm, respectively. Mean aortic pressure, central venous pressure, and left arterial pressure did not change significantly. Also, no change was observed for the left and right pump flows. This totally implantable BVAD showed excellent long‐term performance without any mechanical problems. It is feasible to operate without impairment under physical activity. However, the natural heart dominated the hemodynamic response during exercise under BVAD support. The left and the right pump flows did not increase spontaneously with exercise. We therefore conclude that a servo CO control system is necessary to regulate pump flows even during moderate exercise.
Real Time Monitoring of Oxygen Saturation in Extracorporeal Circulation Using an Optical Reflectance Transducer
Authors: Gamero Fernando U. , Ushizima Mauro R. , Cestari Idágene A.
Published: March 2003

Abstract: A novel optical reflectance transducer for continuous and real time monitoring of oxygen saturation (So2) in extracorporeal tubings during cardiopulmonary bypass (CPB) is described. The optical transducer integrates 2 light‐emitting diodes and a photodiode. The transducer is attached to the extracorporeal tubing by a transparent flow through a 3/8×3/8 inch connector/cuvette. Four transducers were built and evaluated in vitro in a mock extracorporeal system at a controlled So2. The correlation index (r2) between the So2 measured by the transducers and values determined by a commercial blood gas analyzer was 0.998 with an absolute difference < 0.5%. The performance of the transducer was also evaluated during 16 CPB surgeries in patients with an r2 of 0.873 and an absolute difference < 3.5%. The results obtained demonstrate the applicability of the optical reflectance transducer for monitoring So2 in the tubings of the CPB circuit.
Effects of Hemoglobin‐Based Blood Substitutes on Vasoactivity of Rat Aortic Rings
Authors: De Figueiredo Luiz Francisco Poli , Nelson Sharon H. , Mathru Mali , E Silva Mauricio Rocha , Kramer George C.
Published: March 2003

Abstract: Our objective is to characterize the vasoactive properties of a 10%αα diaspirin cross‐linked human hemoglobin (ααHb) and to test the hypothesis that sodium nitroprusside (SNP)‐induced relaxation is inhibited in the presence of ααHb. Experiments were performed on aortic rings from 18 Wistar rats; the rings were suspended in aerated Krebs solution. Changes in isometric tension were measured to increasing concentrations of ααHb (1.8 × 10−9to 10−4M) on phenylephrine (PE)‐induced contraction (3 × 10−7M), on acetylcholine (ACh)‐induced relaxation (10−8 to 10−6M), on SNP‐induced relaxation (10−9 and 10−8M), and on PE‐induced contraction with an endothelin‐1 (ET1) receptor antagonist, BQ123 (10−5M). Control rings received no ααHb. A concentration‐dependent increase of the PE‐precontraction (1.3%, 6.8%, 17.4%, and 34%, respectively) as well as the inhibition and reversal of ACh‐induced relaxation was observed after ααHb. The presence of ααHb decreased the SNP‐induced relaxation in the presence or absence of endothelium. The relaxation induced by SNP was reduced with time in the presence, but not in the absence, of ααHb. In conclusion, although pharmacological modulation of the vasoconstriction is possible with nitric oxide donors, our findings suggest that in the clinical setting, large sustained donor doses may be required.
Atomic Force Microscopic Observation of Mechanically Traumatized Erythrocytes
Authors: Ohta Yuji , Okamoto Hiroshi , Kanno Masahiro , Okuda Tomoko
Published: March 2003

Abstract: Erythrocytes are damaged or stimulated mechanically by artificial organs assisting in circulation. For several decades, a large number of research studies have been conducted to investigate the traumatizing phenomena due to nonphysiological flow conditions. These phenomena are thought to be the physical interaction between the cell membrane and the various fluidic conditions. To elucidate or evaluate the phenomena, however, chemical components emerging into the circulating solution, such as liberated hemoglobin or lactic dehydrogenase (LDH), have been measured as a main parameter. Naturally, the physical reaction caused on the membrane itself cannot be detailed by these parameters because they are the secondary products resulting from the mechanical membrane rupture. The aim of this study is to understand the traumatizing mechanism directly from a microbiological viewpoint. As a first step, we visualized the surface of sheep erythrocytes loaded with shear stress and measured erythrocyte surface roughness by atomic force microscopy (AFM) on a nanometer scale (10−9 m). The constant shear rate was set at 1,800 (1/s), and the exposure time was set at 0.5, 1, and 2 h. We also measured the liberated hemoglobin concentration. As a result, it was found that the fine structure on the cell surface was changed drastically by the stress. It was also found that the surface roughness value increased with the exposure time, and correlated to the hemoglobin concentration. The visualization and the measurement of surface roughness of traumatized erythrocytes by AFM were thought to offer a new parameter for both hemolytic and subhemolytic studies.
Effect of Different Solvents and Crosslinkers on Cytocompatibility of Type II Collagen Scaffolds for Chondrocyte Seeding
Authors: Tsai Ching‐Lin , Hsu Shan‐hui , Cheng Wen‐Ling
Published: March 2003

Abstract: Type II collagen extracted from porcine costal cartilage was evaluated as scaffolds for cartilage tissue engineering. Chemical crosslinkers were employed to improve the mechanical properties and the resistance toward degradation. Films and porous scaffolds were prepared from collagen solutions dissolved in 3% acetic acid (designated A) or in deionized water (designated W) and crosslinked by an epoxy (designated E) or by a carbodiimide (designated C). Immortalized rat chondrocytes and rabbit chondrocytes were used to assess cytocompatibility of crosslinked collagen matrices. Cell adhesion rate onto the films made by different preparations ranked in the order of WE ≥ WC > AC ≥ AE. Cell proliferation ranked in the order of AC > WC > AE ≥ WE. Cells maintained round morphology only on AC and WC films. In 3‐D seeding, AC scaffolds also were found to be the most cytocompatible. WC scaffolds, however, had better dimensional stability. It was concluded that Type II collagen scaffolds, when prepared by using deionized water as the solvent and carbodiimide as the crosslinker, could promote chondrocyte growth and matrix production.
Alternative Timeframes for Hemodialysis
Authors: Vanholder R. , Veys N. , Van Biesen W. , Lameire N.
Published: March 2003

Abstract: Routinely, maintenance hemodialysis is applied according to an alternate day time schedule with dialysis sessions lasting 3 to 5 h. In analogy with continuous ambulatory peritoneal dialysis, a more gradual and more consistent removal pattern could be achieved by modifying this timeframe, e.g., by applying daily hemodialysis and/or by prolonging hemodialysis sessions to 8 h or more. Recently, a number of dialysis units implemented such alternative timeframes. Both the clinical and metabolic status showed dramatic improvements with beneficial effects on blood pressure, anemia, and potassium and phosphate levels. These changes occurred despite decreases in the dosage of the drugs administered to cope with these problems. However, controlled studies comparing morbidity and mortality of these alternative timeframes to the more traditional approaches are lacking at this moment.
Selective Removal of Circulating Immune Complexes from Patient Plasma
Authors: Kunkel Siegfried , Holtz Manfred , Grossjohann Beatrice , Schuett Wolfgang , Klinkmann Horst , Kong Deling , Yamada Ryo , Kimura Hajime , Matic Goran B. , Ramlow Wolfgang , Boeden Hans‐Friedrich
Published: March 2003

Abstract: The principle of a patient‐specific immunoadsorber (PsIA) is demonstrated. Studies with model systems (HSA/anti‐HSA) on immobilization, stability, and leakage form the basis for the presented fast‐performance liquid chromatography (FPLC) and batch experiments, which were conducted using two different protein A adsorbers and autologous and heterologous PsIA systems. Experiments to determine the binding capacity of protein A adsorbers and PsIAs are described. In all experiments, the adsorption of plasma IgG, total protein, and C1q and C3d circulating immune complexes were measured. Plasma of patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus) was investigated. Analysis was performed in both the initial plasma and the flow‐through or supernatant. Results of the investigations using FPLC and batch experiments were compared. Autologous PsIA systems are suitable for the selective removal of elevated levels of circulating immune complexes in the plasma.
Selective Hemapheresis, an Effective New Approach in the Therapeutic Management of Disorders Associated with Rheological Impairment: Mode of Action and Possible Clinical Indications
Authors: Schuff‐Werner Peter , Holdt Birgit
Published: March 2003

Abstract:The in vitro measurement of whole‐blood viscosity, plasma viscosity, and erythrocyte aggregability is easy to perform, but they only allow a partial insight into the complexity of blood flow characteristics; however, they permit definition of the rheological properties of new hemorheological therapeutic modalities such as extracorporeal plasma therapy as described in this paper. Under more theoretical aspects, it becomes obvious that such hemorheological approaches should either improve the vasomotoric properties of blood vessels, reduce the circulating red blood cell concentration, or improve the viscosity by reducing the concentration of hemorheologically relevant plasma proteins. In this review, the rheological effect of a single apheresis treatment with different devices was compared. Due to their differences in selectivity, the extracorporeal methods have different effects on the rheologically relevant plasma proteins, and, therefore, their rheological effectiveness differs remarkably. Today, the classicalblood lettingand plasma exchange treatment have been replaced by erythrapheresis and selective devices for extracorporeal plasma treatment, respectively. For more than 10 years, the following 5 more‐or‐less selective apheresis procedures are commercially available: immunoadsorption, differential filtration, polyanion adsorption by dextrane sulfate as well as by polyacrylate, and polyanion precipitation by heparin as polyanion. The last three procedures are semiselective and, therefore, relatively unspecific whereas immunoadsorption only affects the plasma lipoprotein concentration. Several studies have shown the effective use of extracorporeal hemorheotherapy for the treatment of various diseases including macro‐ and cryoglobulinemia, Raynaud's disease, hyperlipoproteinemia (often characterized by premature atherosclerosis and coronary heart disease and peripheral arterial occlusive disease), cerebral multi‐infarct demention and acute ischemic stroke, sudden hearing loss, and acute occlusion of the central retinal artery.
Hypothermia with Heparin‐Coated Circuits and Low Dose Systemic Heparinization in Neurosurgery
Authors: Hachiro Yoshikazu , Morishita Kiyofumi , Koshima Ryuji , Nakashima Shinji , Takagi Nobuyuki , Tsukamoto Masaru , Abe Tomio , Hashi Kazuo
Published: March 2003

Abstract: The purpose of this study was to evaluate the safety of profound hypothermic circulatory arrest with heparin‐coated circuits and low dose systemic heparinization in the treatment of cerebral aneurysms. Surgery for giant intracranial aneurysms not operable using standard neurosurgical techniques was performed in 8 patients. All patients were placed on cardiopulmonary bypass using the closed‐chest technique, except for the first patient who underwent open‐chest bypass. Heparin was administered systemically (3,000 IU) and into the circuit (1,500 IU). Total circulatory arrest was begun at 20°C. The D‐dimer, α2 plasmin inhibitor‐plasmin complex, thrombin‐antithrombin III, and β‐thromboglobulin concentrations were measured to evaluate the changes in the coagulation and fibrinolytic systems during bypass. There were no neurologic or cardiac complications. None of the indicators of platelet activation, coagulation, or fibrinolysis were elevated. Hypothermic circulatory arrest combined with heparin‐coated circuits and low dose systemic heparinization is safe for use in neurosurgery.
Changes in Lymphocytic Cluster Distribution During Extracorporeal Immunoadsorption
Authors: Schneidewind‐Müller Jana‐Maria , Winkler Roland E. , Tiess Michael , Müller Waltraud , Ramlow Wolfgang
Published: March 2003

Abstract: The success of apheresis treatment is often measured as a decrease in the detected antibodies and an improvement in different disease‐related scores. Sometimes, however, the seriousness of the disease does not correlate with the antibody level. During a period of 8 years, 15 patients (3 myasthenia gravis, 1 multiple sclerosis, 2 systemic lupus erythematosus, 3 alloimmunized kidney transplant, 6 rheumatoid arthritis) were treated by protein A immunoadsorption. Lymphocyte subpopulations (activated T cells, cytolytic T cells, B cells, natural killer cells) and inflammatory proteins (ferritin, C‐reactive protein, α1‐antitrypsin, α2‐macrogobulin) were analyzed. After observing clinical outcomes, the patients could be divided into 2 groups, respectively: Group 1, responding patients with remission of disease; and Group 2, delayed‐responding patients, who required chronic treatment. Group 1 patients characteristically showed a greater increase in activated T and cytolytic T cells which correlated with a greater decrease of B cells. It might be possible that protein A immunoadsorption induced immunomodulation. Further immunological investigation is required to verify these findings.
Aortic Valve Replacement in Patients Age 70 Years and Older: Early and Late Results
Authors: Kawachi Yoshito , Arinaga Kouich , Nakashima Atsuhiro , Toshima Yoshihiro , Kawano Hiroshi , Kosuga Tomokazu
Published: March 2003

Abstract: This retrospective analysis was performed to determine the early and late outcome in patients 70 years and older undergoing aortic valve replacement (AVR). From October 1994 to May 2001, 49 patients (24 men and 25 women, age 70 to 88 years [mean 74 ± 4.6 years]) underwent primary AVR with or without concomitant procedures. Twenty‐one received mechanical valves and 28 bioprostheses. Age was different between both groups: 72 ± 2.3 years (mechanical) and 76 ± 5.1 years (bioprosthetic) (p = 0.0005). Aortic stenosis was present in 25 patients (51%). Follow‐up was 100% complete at a mean follow‐up of 2.9 years (range 0.3–6.5 years). Overall hospital mortality was 4.1% (2/49). There were no postoperative complications in 24% of patients. Postoperative hospital stay or hospital survival was 27 ± 13 days. Survival at 3 and 5 years was 89 ± 5% and 80 ± 7%, respectively. Three late deaths were due to noncardiac causes and 1 each had a cardiac or valve‐related cause (thromboembolism). Other valve‐related complications such as anticoagulant‐related hemorrhage, perivalvular leak, endocarditis, prosthetic valve failure, and reoperation were not noted in any of the 49 patients. The actuarial survival curve was similar in each group of bioprosthetic versus mechanical and septuagenarians versus octogenarians. Under the selection criteria for AVR currently applied in our hospital, geriatric patients showed a satisfactory early outcome and medium‐term survival benefit.