Abstract: We designed a 24-field array and an on-line control box that selects which and how many of 24 fields will conduct electrical charge during functional electrical stimulation. The array was made using a conductive microfiber textile, silver two-component adhesive, and the conductive ink imprint on the polycarbonate. The control box comprised 24 switches that corresponded one-to-one to the fields on the array. Each field could be made con- ductive or nonconductive by simple pressing of the corre- sponding push-button type switch on the control box. We present here representative results of the selectivity of the new electrode measured in three tetraplegic patients dur- ing functional electrical stimulation of the forearm. The task was to generate finger flexion and extension with min- imal interference of the wrist movement during lateral and palmar grasps. Therapists determined the appropriate pat- tern that lead to effective grasping, lasting on average 5 min per stimulation channel in the first session. This opti- mal conductive pattern (size and shape) provided effective finger flexion and extension with minimal wrist flexion/ extension and ulnar/radial deviations ( < 10 degrees). The optimal size and shape of the electrode in all cases had a branched pattern. The selection of the optimal stimulation site was achieved without moving the electrode. The size and shape were reproducible in the same subject from session to session, yet were different from subject to sub- ject. The optimal electrode size and shape changed when subjects pronated and supinated their forearm. The control box includes a program that can dynamically change the number and sites of the conductive fields; hence, it is fea- sible to use this during functional movements. Subjects learned how to determine the optimal electrode pattern; hence, these electrodes could be effective for home usage. Key Words: Electrical stimulation—Electrode— Selective—Surface—Conductive fields.

Abstract: To evaluate the effects of electrical stimulation on denervated muscles in spinal cord injured humans, the EU Project RISE was started in 2001. The aims of this project are: to design and build sufficient stimulators; to develop stimulation protocols by means of mathematical models, animal experiments, and practice in humans with denervated lower limbs; to develop examination methods and devices for evaluation of electrical stimulation training effects; and to acquire basic scientific knowledge on denervated and stimulated denervated muscle. In the clinical study 27 spinal cord injured individuals were included, furthermore 13 pilot patients participated. After a series of initial examinations they underwent an electrical stimulation program for their denervated lower limb muscles. Some of the patients have already follow up examinations. A marked increase of muscle mass and quality was observed, the trophic situation of the denervated lower limbs had improved obviously.

Abstract: In this study we investigated the biocompatibility of collagen-chitosan-sodium hyaluronate (Col-Chi-NaHA) complexes and cornea tissue, and the feasibility of Col-Chi-NaHA complexes as substrates for cultivating rabbit corneal cells. Different components of Col-Chi-NaHA complexes were prepared and tested. A circular complex film with a diameter of 6 mm was inserted into rabbit stomal pocket and traced for a period of 5 months. Clinical examination was made. Rabbit limbal corneal epithelial cells, corneal endothelial cells, and keratocytes were cultured primarily on complexes. Phase contrast microscope examination was made daily. Histological, immunohistochemical, and scanning electron microscopic examinations were carried out. The complexes of 20% collagen, 10% chitosan, and 0.5% sodium hyaluronate showed rather weak corneal edema and other responses. The degradation of materials was obvious after 5 months. Corneas were transparent and translucent. Cells seeded on Col-Chi-NaHA were allowed to proliferate and partly form confluent monolayer after 9 days in culture. Cultured cells were well attached to the complexes of 20% collagen, 10% chitosan, and 0.5% sodium hyaluronate, or 10% chitosan and 0.5% sodium hyaluronate. The results showed that Col-Chi-NaHA complexes had good biocompatibility with cornea. The complexes can degrade and be absorbed in cornea. Col-Chi-NaHA complex may be a suitable substrate for cultivating corneal cells and a feasible material as a scaffold of tissue-engineered cornea.

Abstract: Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years FES-training the muscle cryosections present mainly large round myofibers. In the FES-trained muscles the regenerative events are present, but at a lower rate than long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 +/- 1.3 in FES vs. 2.3 +/- 2.3 in DDM, mean +/- SD, P = 0.011). In our opinion this is a sound additional evidence of effectiveness of the Kern's electrical stimulation protocol for FES of DDM. In any case, the overall results demonstrate that the FES-training is safe: at least it does not induce more myofiber damage/regeneration than denervation per se.

Abstract: A major part of developing rotary blood pumps requires the optimization of hemolytic properties of the entire pump. Application of a suited computational fluid dynamics (CFD)-based hemolysis model allows approximation of blood damage in an early phase of the design process. Thus, a drastic reduction of time- and cost- intensive hemolysis experiments can be achieved. For the MicroDiagonal Pump (MDP), still under development at Helmholtz-Institute in Aachen, Germany, different pump configurations have been analyzed, both numerically and experimentally. The CFD model of the pump has been successfully validated based on the comparison of the pressure head curves (H-Q curves), as discussed in a prior publication. In the present study, the authors focus on the development of a semiempiric blood damage model using the CFD and in vitro hemolysis data. On the one hand, mean key characteristics (shear stress and exposure time) and other characteristics affecting blood damage have been calculated based on numerical data. On the other hand, in vitro hemolysis tests have been accomplished in order to determine the hemolytic curves of two different pump configurations (with the same impeller but different tip clearances). Finally, a new function based on a general power law has been defined by means of the mean key characteristics. The unknown constants of the function have been determined by multidimensional regression analysis using the hemolytic curves. For the final validation of this new blood damage model, the calculated and the in vitro obtained hemolysis indices at the specific VAD operating point have been compared for all pump configurations. The comparison showed an excellent agreement, both qualitatively and quantitatively.

Abstract: A major limitation of many functional electrical stimulation (FES) applications is that muscles tend to fatigue very rapidly. It was hypothesized that FES-induced muscle fatigue could be reduced by randomly modulating the pulse frequency, amplitude, and pulse width in a range of ± 15%. Seven subjects with spinal-cord injuries participated in this study. FES was applied to quadriceps and tibialis anterior muscles using surface electrodes. Iso- metric force was measured, and the time for the force to drop by 3 dB (fatigue time) was compared between trials. Four different modes of FES were applied in random order: constant stimulation, randomized frequency, ran- domized amplitude, and randomized pulse width. There was no significant difference between the fatigue-time measurements for the four modes of stimulation ( P = 0.329). Therefore, random modulation appeared to have no effect. Based on an observed correlation between maximum force measurements and trial order, we con- cluded that having 10-min rest periods between trials was

Abstract: Appropriate software tools may improve communication and ease access to knowledge for research groups. A weblog is a website which contains periodic, chronologically ordered posts on a common webpage, whereas a wiki is hypertext-based collaborative software that enables documents to be authored collectively using a web browser. Although not primarily intended for use as an intranet-based collaborative knowledge warehouse, both blogs and wikis have the potential to offer all the features of complex and expensive IT solutions. These tools enable the team members to share knowledge simply and quickly-the collective knowledge base of the group can be efficiently managed and navigated.

Abstract: Artif Organs, 29: 239 -241, 2005 Introduction: Spinal cord injured patients with a suprasacral lesion usually develop a spastic bladder. The hyperreflexia of the detrusor and the external sphincter causes incontinence and threatens those patients with recurrent urinary tract infections (UTI), renal failure, and autonomic dysreflexia. All of these severe disturbances may be well managed by sacral deafferentation (SDAF) and implantation of an anterior root stimulator. Material and Method: Between September 1986 to December 2002, 464 paraplegic patients (220 female, 244 male) received a SDAF-SARS. Almost exclusively the SDAF was done intradurally, which means with one operation field there can be done two steps (SDAF and SARS). Results: 440 patients have a follow-up with 6.6 years (at least 6 months-17 years) The complete deafferentation was successful in 94.1%. A total of 420 paraplegics may use the SARS for voiding (frequency 4.7 per day) and 401 use it for defecation (frequency 4.9 per week). Continence was achieved in 364 patients (83%). UTI declined from 6.3 per year preoperatively to 1.2 per year postoperatively. Kidney function presented stable. Early complica- tions were 6 CSF leaks, 5 implant infections. Late complications with receiver or cable failures made us do surgical repairs in 34 paraplegics. A step-by-step program for trouble-shooting differentiates implant failure and myogenic or neurogenic failure. Conclusion: SDAF is able to restore the reservoir function of the urinary bladder and to achieve continence. Autonomic dysreflexia disappeared in most of the cases. By means of an accurate adjustment of stimulation parameters it is possible to accomplish low resistance micturition. The microsurgical technique requires an intensive education. One has to be able to manage late implant complications. Editorial Comment: This is a very extensive and most impressive experience with a technique that is confined in usage to a very few centers. Perhaps this is because of the "intensive education" that the authors state is required in the microsurgical technique. In addition to what is described in the abstract, the following data from the short, sparsely referenced article are relevant: 1) 8 patients required a second deafferentation at the conus level to achieve a complete interruption of hyperreflexia; 2) in 22 of the 364 patients achieving continence the additional implantation of an artificial sphincter was required and 3) autonomic dysreflexia disappeared in all but 2 of 187 cases. The authors also state that implants with cable plugs could make repair procedures easier and the development of microelectronic devices without cables could help to avoid implant complications. The authors conclude by stating "...the satisfaction of our para- plegic patients with the outcome after SDAF and (sacral anterior root stimulation) is very high and they improve in independence and in quality of life." Sexual aspects are not considered in this article, but it can be assumed that reflex erections, where present, were lost with the complete transection of the afferent dorsal roots S2 to S5.

Abstract: We developed a novel simple method for making functional myocardial cell sheets that may be used as transplants. Polymerized human fibrin-coated dishes were prepared with fibrinogen monomers mixed with thrombin. Neonatal rat cardiomyocytes cultured on these dishes formed myocardial cell sheets within 4 days. These cell sheets were easily dissociated intact from the polymerized fibrin layer, because the fibrin had been digested by intrinsic protease. Two overlaid myocardial cell sheets exhibited synchronized spontaneous beating and captured artificial pacing. Optical mapping confirmed that the conduction of the action potential between two partially overlaid myocardial cell sheets was established, and the action potential propagated across the junction without any delay. Transplanted three-layered myocardial cell sheets exhibited strong spontaneous beating and showed well-differentiated striations and an increase in cell size. This simple method of cell sheet engineering may also be applicable for various other cell types.

Abstract: An increased oxidative stress is now considered one of the major risk factors in chronic renal failure (CRF) patients that may be exacerbated by dialysis. It has been postulated that this increased oxidative stress might cause an augmented red blood cell (RBC) membrane lipid peroxidation with the consequent alteration in membrane deformability. The aim of this study was to evaluate RBC susceptibility to an in vitro induced oxidative stress and RBC antioxidant potential in different groups of CRF patients undergoing different substitutive treatment modalities. Fifteen end-stage CRF patients were evaluated in conservative treatment, 23 hemodialysis (HD) patients, 15 continuous ambulatory peritoneal dialysis (CAPD) patients, 15 kidney transplanted patients, and 16 controls. Their RBCs were incubated with the oxidative stress-inducing agent tert-butylhydroperoxide both in the presence and in the absence of the catalase inhibitor sodium azide, and the level of malondialdehyde (MDA) (a product of lipid peroxidation), was measured at 0, 5, 10, 15, and 30 min of incubation. In addition, the RBC content of reduced glutathione (GSH) was measured by HPLC. As opposed to the controls, RBCs from end-stage CRF patients exhibited an increased sensitivity to oxidative stress induced in vitro, both in the absence and presence of a catalase inhibitor, as demonstrated by a significantly higher level of MDA production at all the incubation times (P < 0.05). Different substitutive treatments had different impacts on this phenomenon; CAPD and kidney transplantation were able to normalize this alteration while HD was not. GSH appeared to be related to the increase in RBC susceptibility to oxidative stress; its content being significantly elevated in end-stage CRF and HD patients as compared with CAPD and transplanted patients and controls (P < 0.05). No significant changes were observed in the RBC glutathione content during the HD session. The increase of GSH in RBCs of end-stage CRF and HD patients seems to indicate the existence of an adaptive mechanism under increased oxidative stress occurring in vivo. Unlike HD, the beneficial effect of CAPD on the anemia of dialysis patients might partly be due to a condition of lower oxidative stress that might in addition counterbalance the cardiovascular negative effects of dislipidemia of CAPD patients.

Abstract: A mock circulatory loop, which simulates the human circulatory system, is needed to bench test the various versions of continuous flow (CF) left ventricular assist devices (LVADs). This article describes the design and initial testing of such a loop. The loop consists of: (1) pulsatile left and right cardiac simulators; (2) air/water tanks to model the venous and arterial compliances; (3) tygon tubes to model the venous, arterial, and other system flow resistances; and (4) a tuning clamp to model the variation in system resistance characteristics under different cardiac pressure/flow conditions. Several loop measurements were carried out without an LVAD to verify the cardiovascular modeling of a healthy person in sleep, rest, and physical activity, and in different pathological states, and compared to the data found in the literature to validate the loop performance prior to LVAD testing.

Abstract: Tissue engineering approaches for treating degenerative intervertebral discs aim to promote tissue regeneration then retard or even reverse the degenerative process. A gelatin/chondroitin-6-sulfate/hyaluronan tri- copolymer was developed to serve as a bioactive scaffold that could help human nucleus pulposus (NP) cells to pre- serve their cell viability/proliferation and promote matrix synthesis. Each scaffold was seeded with 1 ¥ 10 6 mono- layer-expanded human NP cells and then cultured in vitro. Over a 4-week cultivation period, cell-scaffold hybrids demonstrated active cell viability/proliferation and a pro- gressive increase in net production of glycosaminoglycans. In comparison to monolayer cells, scaffold-cultured cells showed significantly higher mRNA expression in collagen II, aggrecan, Sox9, TGFb1, and TIMP1. Expression of mRNA was significantly suppressed in collagen I, col- lagen X, IL1, and Fas-associating death domain protein. Histological studies showed newly synthesized glyco- saminoglycans deposits and collagen II in scaffolds. These results indicate that the tri-copolymer scaffold could be considered as a promising bioactive scaffold for regenerating human NP. Key Words: Gelatin—Chon- droitin-6-sulfate —Hyaluronan—Human—Intervertebral disc—Tissue engineering.

Abstract: Polymer heart valves have been under investigation since the 1960s, but their success has been hampered by an overall lack of durability mainly due to calcification of the leaflets and a relatively high rate of thromboembolic complications A new polymer (Quatromer) trileaflet design was tested for its thrombogenic potential and was compared to that of existing prosthetic heart valves routinely implanted in patients: a St Jude Medical bileaflet mechanical heart valve (MHV) and a St Jude porcine bioprosthetic tissue valve The valves were mounted in a left ventricular assist device and the procoagulant activity of the platelets was measured using a platelet activation state (PAS) assay The PAS measurements indicated that the platelet activation level induced by the polymeric valve was very similar to that induced by the St Jude Medical MHV and the St Jude tissue valve No significant difference was observed between the three valves, indicating that they have a comparable thrombogenic potential

Abstract: Atherosclerosis is accelerated in hemodialysis patients. Intima media thickness (IMT) is a strong predictor for cardiovascular events in the general population. Using B-mode ultrasonography, IMT in the common carotid arteries was measured in 99 nondiabetic hemodialysis patients (44 women and 55 men, mean age 53.1 years and mean dialysis duration 45.8 months). During a follow-up of 42.4 ± 19.5 months, 33 patients died, 19 (57.6%) of them of cardiovascular causes. In these 19 patients IMT was significantly higher (0.89 vs. 0.69 mm) than in those who survived. Correlation between cardiovascular mortality and IMT was found. Patients were divided in relationship to the tertiles of IMT and the risk for cardiovascular death was progressively higher from the first tertile of IMT onward (P < 0.0006). IMT turned out to be an independent predictor of cardiovascular death (P < 0.025). According to our results IMT may be usefully applied for cardiovascular mortality risk stratification in nondiabetic hemodialysis patients.

Abstract: Background: Patients with chronic renal failure (CRF) are at increased risk of atherosclerosis development. One of the major steps in pathogenesis of atherosclerosis is formation of foam cells. Scavenger receptor CD36 is among the major receptors for oxidized low density lipoproteins (oxLDL) and therefore it plays a crucial role in foam cell formation. The aim of the present study was to investigate the expression of CD36 on blood monocytes of CRF patients. Methods: Expression of CD36 on blood monocytes of CRF patients treated with hemodialysis (HD), peritoneal dialysis (PD), those not yet on dialysis (predialysis), and controls was assessed with the use of flow cytometry. Additionally, the major lipid peroxidation markers, malondialdehyde (MDA) and 4-hydroxyalkenals (HAE), were measured. Further, impact of treatment with HMG-CoA reductase inhibitors (statins) on CD36 expression in CRF patients was evaluated. Results: Expression of monocyte CD36, measured as mean fluorescence intensity (MFI) was significantly higher in HD and PD patients, when compared to controls without renal insufficiency (respectively: 1011 ± 288 and 1000 ± 309 vs. 710 ± 313; P < 0.01 for both groups). This was not the case in predialysis group (828 ± 363 vs. 710 ± 313). Higher concentrations of lipid peroxidation indicators, MDA and HAE were observed in all three subgroups of CRF patients (2.1 ± 0.51, 2.02 ± 0.27, and 1.81 ± 0.53 µm in HD, PD, and predialysis group, respectively, vs. 1.13 ± 0.59 µm in controls; P < 0.01). Patients treated with statins showed significantly lower CD36 expression than patients without statin therapy. Conclusions: The present study, for the first time, demonstrates increased expression of CD36 scavenger receptor in CRF patients. This may be a possible risk factor for accelerated atherogenesis observed in this group of patients.

Abstract: The ability to engineer cardiac tissue in vitro is limited by the absence of a vasculature. In this study we describe an in vivo model which allows neovascularization of engineered cardiac tissue. Three-dimensional cardiac tissue, termed "cardioids," was engineered in vitro from the spontaneous delamination of a confluent monolayer of cardiac cells. Cardioids were sutured onto a support framework and then implanted in a subcutaneous pocket in syngeneic recipient rats. Three weeks after implantation, cardioids were recovered for in vitro force testing and histological evaluation. Staining for hematoxylin and eosin demonstrated the presence of viable cells within explanted cardioids. Immunostaining with von Willebrand factor showed the presence of vascularization. Electron micrographs revealed the presence of large amounts of aligned contractile proteins and a high degree of intercellular connectivity. The peak active force increased from an average value of 57 microN for control cardioids to 447 microN for explanted cardioids. There was also a significant increase in the specific force. There was a significant decrease in the time to peak tension and half relaxation time. Explanted cardioids could be electrically paced at frequencies of 1-5 Hz. Explanted cardioids exhibited a sigmoidal response to calcium and positive chronotropy in response to epinephrine. As the field of cardiac tissue engineering progresses, it becomes desirable to engineer larger diameter tissue equivalents and to induce angiogenesis within tissue constructs. This study describes a relatively simple in vivo model, which promotes the neovascularization of tissue-engineered heart muscle and subsequent improvement in contractile performance.

Abstract: An algorithm designed to automatically control insulin delivery was tested in rats with Type 1 diabetes. This nonlinear algorithm included a fading memory component of proportional and derivative errors in order to simulate normal insulin secretion. Error-weighting functions for the proportional and derivative terms were used with a performance index designed for error adaptation. In the first version of the algorithm, the proportional gain was adaptively varied. In the second version, a low rate of basal insulin delivery was adaptively varied. Six 6-h studies with each version were conducted using frequent blood sampling and intravenous insulin delivery. In Version 2 studies, blood glucose levels during the last two hours were well-controlled and significantly lower than in Version 1 (118 +/- 2.0 vs. 130 +/- 2.9 mg/dL). Neither version produced hypoglycemia. Future research using this algorithm needs to focus on automated glucose sensing in combination with insulin delivery.

Abstract: Measurements of the rheobase and chronaxie can be used to define the excitability of nerves and muscles. The aim of this study was to obtain a record over many weeks of changes in the rheobase and chronaxie of denervated rabbit tibialis anterior muscle (TA). A custom-built electronic stimulator was implanted into the peritoneal cavity of New Zealand White rabbits. Large stainless steel electrodes were placed on the denervated TA muscle. Rheobase and chronaxie were measured noninvasively at weekly intervals by means of a laptop PC, which communicated with the stimulator via a radio-frequency link. At each setting the denervated TA was palpated manually to detect the response of the muscle. During the first few days after denervation the rheobase increased transiently to 0.8 +/- 0.13 mA, approximately twice the value for normal innervated muscle, then decreased to normal for the remainder of the experimental period. Chronaxie underwent a significant 3-fold increase from 4.5 +/- 1.1 ms to 14.1 +/- 1.1 ms during the first two weeks of denervation and remained elevated throughout. The custom-built implantable electronic stimulator allowed changes in muscle excitability to be studied over a long period of denervation within individual animals, providing an accurate assessment of the time course of denervation-induced changes in muscle excitability.

Abstract: Background Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting. Methods 24 prevalent patients on regular LDL apheresis treatment were included in the study. Bradykinin, prekallikrein, and HMW kininogen were measured during a single LDL apheresis at different sites of the systems. Results LDL apheresis with DSC and DALI was associated with an extreme release of bradykinin after the passage of plasma or blood through the LDL adsorbers as well as with a decrease of prekallikrein and HMW kininogen during the course of the treatment. Bradykinin release exceeded the degradation capacity of the kininase II, since markedly elevated bradykinin concentrations were observed in the arterial line of the extracorporeal circuits of both systems. This was not associated with anaphylactoid reactions. In contrast to the treatments with DSC and DALI, the HELP system did not lead to any activation of the kallikrein-kinin system. Conclusion From our data we conclude that angiotensin converting enzyme (ACE) inhibitors are contraindicated in patients on LDL apheresis with the DSC and the DALI system. Because the HELP system does not activate the kallikrein-kinin system, patients who need ACE inhibitors are predisposed for this LDL apheresis procedure.

Abstract: Multi-electrode devices are constantly evolving toward a state where complexity and reliability are adequate for providing a breakthrough in visual cortical stimulation allowing the blind to recover partial vision Yet few research teams have focused on the development of the front-end subsystem that transforms an input image from a camera into stimulation commands This article collects state-of-the-art knowledge about the appearance and organization of phosphenes, and previous work in image processing dedicated to visual cortical stimulation Observations and hypothesis about important issues are highlighted, and six image processing strategies that could be used in such a subsystem are presented, from the most optimistic that use brightness modulation to emulate grayscale to the most conservative that use only on/off phosphene evocation

Abstract: In the frame of the EU-funded RISE project, patients with lower motor neuron lesion and denervated and degenerated muscles are treated with electrical stimulation, with the aim of restoring muscle mass and force. Spiral computer tomography from the hip joint down to the knee joint is used to gather three-dimensional data on the upper leg tissue. These data are analyzed in order to monitor tissue changes induced by the electrical stimulation treatment. Especially the data representing muscle tissue and bone tissue were isolated for measurement purposes. Computer models and models made with rapid prototyping methods were used to display and demonstrate changes in muscle shape and size, as well as position relative to bone. Results showed that time and spatial dependencies of muscle growth can be monitored and studied quantitatively and qualitatively with the aid of a three-dimensional data set displayed on the computer screen or in the form of plastic models. These first results indicate muscle growth and an increase in bone density.

Abstract: Rational design of blood-wetted devices requires a careful consideration of shear-induced trauma and activation of blood elements. Critical levels of shear exposure may be established in vitro through the use of devices specifically designed to prescribe both the magni- tude and duration of shear exposure. However, it is exceptionally difficult to create a homogeneous shear- exposure history by conventional means. This study was undertaken to develop a Blood Shearing Instrument (BSI) with an optimized flow path which localized shear exposure within a rotating outer ring and a stationary conical spindle. By adjustment of the rotational speed and the gap dimension, the BSI is designed to generate shear stress magnitudes up to 1500 Pa for exposure time between 0.0015 and 0.20 s with a pressure drop of 100 mm Hg. Computational fluid dynamics (CFD) revealed that a flow path designed by first-order analysis and intuition exhib- ited unfavorable pressure gradient, vortices, and undesir- able regions of reverse flow. An optimized design was evolved utilizing a parameterized geometric model and automatic mesh generation to eliminate vortices and rever- sal flow and to avoid unfavorable pressure gradients. Anal- ysis of the flow and shear fields for the extreme limits of the shear gap demonstrated an improvement in homoge- neity due to shape optimization and the limitations of an annular shear device for achieving completely uniform shear exposure. Key Words: Hemolysis—Shear stress history—Left ventricular assist device—Computational fluid dynamics—Optimization.

Abstract: Allogeneic cultured dermal substitute (CDS) was prepared by cultivating fibroblasts on a two-layered spongy matrix of hyaluronic acid (HA) and atelo-collagen (Col). CDS can be cryopreserved and transported to other hospitals in a frozen state. To evaluate cell viability, cell growth, and release of VEGF after long-term cryopreservation, the CDS was cryopreserved at -85 degrees C or -152 degrees C for a given period. We measured cell viability immediately after thawing and cell growth in CDS that was recultured for 1 week after thawing. In addition, the amount of vascular endothelial growth factor (VEGF) released from CDS that was recultured for 1 week after thawing was measured. The cell viability and cell growth of control CDS that was thawed within 3 weeks after freezing was 56.2% and 132.7%, respectively. The cell viability and cell growth of the CDS that was cryopreserved at -85 degrees C for 6 months was 43.4% and 119.7%, respectively. When cryopreserved at -152 degrees C for 1 year, the cell viability and cell growth was 52.0% and 110.8%, respectively. These values were comparable to those of the control. The amount of VEGF released from CDS cryopreserved at -85 degrees C for 6 months (491.0 pg/mL) or at -152 degrees C for 1 year (586.8 pg/mL) was comparable to that of the control CDS (587.3 pg/mL). In contrast, the amounts of VEGF released from CDS cryopreserved at -85 degrees C for 1 year (322.5 pg/mL) or at -152 degrees C for 2 years (210.8 pg/mL) were low, with a marked decrease in cell viability and cell growth. These findings suggest that CDS cryopreserved at -85 degrees C for 6 months or at -152 degrees C for 1 year maintains sufficient cell viability and the ability to proliferate and release a significant amount of VEGF. The release of VEGF from CDS after long-term cryopreservation is a useful therapeutic effect, and is important for clinical use.

Abstract: : Background: On-line hemodiafiltration (HDF) represents the supreme blood purification modality for end-stage renal disease (ESRD) patients. Large-volume infusion of on-line prepared substitution fluid may, however, expose patients to inflammatory contaminants. As a result, on-line HDF might aggravate chronic inflammation, which correlates with malnutrition, cardiovascular disease, and mortality among ESRD patients. Methods: In a multicenter cross-over study, 27 ESRD patients were randomly assigned to treatment with on-line HDF and low-flux hemodialysis (HD). After 6 months, patients were crossed to the other treatment modality, and treatment continued for another 6 months. Both on-line HDF and low-flux HD were conducted with polysulfone membranes and ultrapure dialysis fluid. Samples were drawn at the end of each treatment period. Results: Inflammatory parameters were elevated in the study population when compared to healthy controls. Induction of interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor α (TNF-α) was comparable for on-line HDF and low-flux HD, and there was no intradialytic increase in cytokine production. As a result, interleukin-6 (IL-6) plasma levels did not differ significantly between the two treatment modalities. Similarly, no difference between on-line HDF and low-flux HD was observed for C-reactive protein (CRP) and albumin. Markers of endothelial cell activation (soluble intercellular and vascular cell adhesion molecules sICAM-1 and sVCAM-1) as well as the cardiovascular risk marker cardiac troponin T (cTnT) remained elevated compared to healthy subjects, but showed no difference between the two treatment modalities. Conclusions: On-line HDF, as the most effective renal replacement therapy, does not provoke inflammatory response and is both safe and highly biocompatible.

Abstract: The aim of this work is to construct a com- putational fluid dynamics model capable of simulating the transient non-Newtonian process of apheresis. A Lagrangian-Eulerian model has been developed which tracks the blood particles within a two-dimensional flow configuration. Within the Eulerian method, the fluid mass and momentum conservation equations within the separa- tor are solved using the density and the viscosity is calcu- lated from the blood particle concentrations. Subsequently, the displacement of the blood particles is calculated with a Lagrangian method. Hawksley's model for the density of supensions is used in the variable density calculation. The viscosity is calculated with two models based on Vand's rigid particle suspension viscosity concepts, followed by the flow field calculation in the separator. Simulations were performed for various inlet hematocrit values and separa- tor lengths. The simulations are in satisfactory agreement with experimental results reported in literature, indicating a complete separation of plasma and red blood cells (RBCs), as well as nearly complete separation of red blood cells and platelets. No hemolysis was observed in the sim- ulations because the shear rate remained under the criti- cal value of 150 N/m 2 . Ke y Words: Blood separation —Apheresis—Centrifugation—Particle flow—Computa- tional fluid dynamics—Variable viscosity.

Abstract: Clinical use of heart assist devices is often associated with thromboembolic complications. We hypothesized that platelets may be activated in patients receiving assist devices and examined expression of the platelet activation markers CD62, CD63, and thrombospondin using flow cytometry in eight patients with Novacor left ventricular assist system (LVAS) or Berlin Heart. Patients with end-stage heart failure had elevated expression of platelet activation markers before insertion of the assist device. While CD62 (P < 0.05) and thrombospondin expression (n.s.) decreased by the 14th postoperative day, the CD63 expression remained elevated (n.s.). A good correlation was found between CD62 and thrombospondin expression (r = 0.72). Bleeding time ex vivo indicated platelet dysfunction during the first 4 weeks after implantation. No relation between expression of platelet activation markers and bleeding time ex vivo were found. In conclusion, expression of the platelet activation markers CD62, CD63, and thrombospondin is increased in patients with end-stage heart failure before device placement and shows prolonged elevation during the assist period. Future studies in larger patient populations are necessary to identify new and specific markers of platelet activation in this clinical setting.

Abstract: Artificial blood pumps are today's most promising bridge-to-recovery (BTR), bridge-to-transplant (BTT), and destination therapy solutions for patients suffering from intractable congestive heart failure (CHF). Due to an increased need for effective, reliable, and safe long-term artificial blood pumps, each new design must undergo failure and reliability testing, an important step prior to approval from the United States Food and Drug Administration (FDA), for clinical testing and commercial use. The FDA has established no specific standards or protocols for these testing procedures and there are only limited recommendations provided by the scientific community when testing an overall blood pump system and individual system components. Product development of any medical device must follow a systematic and logical approach. As the most critical aspects of the design phase, failure and reliability assessments aid in the successful evaluation and preparation of medical devices prior to clinical application. The extent of testing, associated costs, and lengthy time durations to execute these experiments justify the need for an early evaluation of failure and reliability. During the design stages of blood pump development, a failure modes and effects analysis (FMEA) should be completed to provide a concise evaluation of the occurrence and frequency of failures and their effects on the overall support system. Following this analysis, testing of any pump typically involves four sequential processes: performance and reliability testing in simple hydraulic or mock circulatory loops, acute and chronic animal experiments, human error analysis, and ultimately, clinical testing. This article presents recommendations for failure and reliability testing based on the National Institutes of Health (NIH), Society for Thoracic Surgeons (STS) and American Society for Artificial Internal Organs (ASAIO), American National Standards Institute (ANSI), the Association for Advancement of Medical Instrumentation (AAMI), and the Bethesda Conference. It further discusses studies that evaluate the failure, reliability, and safety of artificial blood pumps including in vitro and in vivo testing. A descriptive summary of mechanical and human error studies and methods of artificial blood pumps is detailed.

Abstract: Although continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VADs) are being clinically used, their effects on aortic blood flow, as a measure of overall blood distribution, remain unclear. In acute VAD support animal experiments, our group has described a zone of turbulent mixing in the aortic arch. The objective of this study was to confirm this finding in the controlled setting of an adult mock circulation, simulating ventricular pathophysiologic states (normal and failing ventricle). CF and PF flow VADs were connected to ventricular apical inflow and ascending aorta (AA) or descending aorta (DA) outflow cannulae. Cardiovascular pressure and flow waveforms were recorded at varying levels of VAD bypass resulting in four test conditions: (i) CF-AA; (ii) CF-DA; (iii) PF-AA; and (iv) PF-DA. Confirming the animal data, no differences in mean aortic flow between CF and PF VADs were found, and significantly lower mean aortic arch flow with DA cannulation was noted. Mean aortic root flow decreased with increasing VAD bypass flow. As in the animal studies, despite similar mean flow rates, significant differences in waveform morphology were observed for AA and DA outflow graft locations and varying levels of VAD bypass. At 100% VAD support in the failing heart, PF restored waveform pulsatility to normal baseline while CF resulted in little pulsatility. These results confirm our earlier findings in the animal model, suggesting that outflow graft location may have a significant effect on aortic blood flow distribution. The long-term implications of these findings are being examined in ongoing studies.

Abstract: Photoelectric dyes, which absorb light and convert photon energy to electric potentials, have been previously shown to stimulate retinal neurons in culture. In this study, a photoelectric dye was coupled to a polyethylene film surface and tested in vitro using retinal tissues from chick embryos at the 12-day embryonic stage, at which time outer segments of retinal photoreceptor cells have not yet developed. Carboxyl moieties were introduced to a polyethylene film surface by fuming nitric acid, and then a photoelectric dye, 2-[2-[4-(dibutylamino)phenyl]ethenyl]-3-carboxymethylbenzothiazolium bromide, was coupled to the film through amide linkage. Intracellular calcium elevation was observed with Fluo-4 in retinal tissues placed on the dye-coupled polyethylene film, in contrast to retinal tissues which had no contact with the film. The response was inhibited by calcicludine, a voltage-gated calcium channel blocker, and also by extracellular calcium depletion. The photoelectric dye, coupled to the polyethylene film surface, absorbed light under a dissecting microscope and stimulated neurons in retinal tissues, showing that the dye-coupled film could be used as a prototype of retinal prostheses.