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ZusammenfassungIn klinischen Studien ist die Wirksamkeit der Prophylaxe mit Heparin zur Verhütung von Venenthrombosen und Lungenembolien im Verlauf der letzten 20 Jahre statistisch überzeugend gesichert worden. Die Ergebnisse klinischer Studien dürfen allerdings nicht als Endresultat klinischer Forschung angesehen werden. Die Resultate einer randomisierten klinischen Studie lassen zunächst im Sinne eines Basiswertes die Nutzen-Risiko-Relation eines Medikamentes erkennen. In klinischen Studien werden spezielle Patientenkollektive geprüft, die Ergebnisse lassen sich daher häufig nicht unmittelbar in Indikation und Kontraindikation auf einen individuellen Patienten übertragen. Für den praktizierenden Kliniker ist es notwendig, diese Entscheidungshilfen der zugängigen Standardliteratur zu entnehmen. Es wird dargelegt, wie wenig informativ Indikationen und Kontraindikationen zur Heparinprophylaxe in Fachinformationen und Roter Liste, speziell unter dem Gesichtspunkt der Risikosituation des Patienten, dargelegt werden. Konsensus-Konferenzen und Empfehlungen von ärztlichen Experten sind notwendig, um in der Praxis die Resultate klinischer Studien auf individuelle Patienten und Risiko-Nutzen-Überlegungen zu übertragen. Endziel ist es, die Ergebnisse klinischer Studien bei der antithrombotischen Therapie so umzusetzen, daß die Sicherheit erhöht wird, ohne daß die Wirksamkeit vermindert wird.

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The aim of this double blind placebo controlled crossover study is to show that apart from decreasing blood pressure felodipine improves microcirculation. 30 patients with essential hypertension and manifest microangiopathy were included. No patients dropped out on account of side effects although these occunocd in the expected frequencies. The study phases each extended for a week (10 mg/d felodipine or locspectively a placebo). Blood pressure, blood and serum values, nail fold capillary circulation and oxygen partial pressure in muscle welOC measUlocd. The blood pressure in the placebo phase remained constant. The increase of erythrocyte velocity in cutaneous capillaries and oxygen partial pressure in muscle and the decrease of poorly supplied muscle areas caused by felodipine relevantly improved the microcirculation of skin and muscle by 50% and 30%. The vasomotor reserve increased by 50% owing to an antispastic effect of the substance. A rheological effect was observed in the form of a decrease in plasma viscosity. Felodipine significantly and loclevantly decreased by 10% the systolic and diastolic blood pressures. Apart from decreasing blood pressure Felodipine causes a relevant and significant global improvement of microcirculation in skin and skeletal muscle tissue.

Objective: Since plateletpheresis is being used increasingly, it is important to regard quality control to check health risks for donors and to exclude these. Design: Controlled randomised prospective open comparative study. Setting: Department of Transfusion Medicine of a University Clinic. Participants: 112 platelet donors were examined. Interventions: Prior to and after plateletpheresis platelet reactivity was determined. The platelet concentrates in the two groups of 56 donors each were produced using either the cell separator ‘CS-3000’ and the collecting chamber PLT 30TM with the OmnixTM system (group I) or the cell separator ‘AS-104’ (group II). Results: In group I five donors showed a pathologically increased platelet reactivity (p = 0.1297) after plateletpheresis. In group II there were 10 donors with a pathologically increased platelet reactivity (p = 0.0046) after plateletpheresis. The mean concentration of platelets was reduced by separation using the CS-3000 Omnix from 238 ± 49 · 103/µl to 172 ± 32 · 103/µl (68 ± 27 · 103/µl) and from 243 ± 53 · 103/µl to 180+31 · 103/µl (63 ± 33 · 103/µl) using the AS-104. In the first case the platelet yield was 3.9 1011 platelets/concentrate, in the latter case it was 2.9 · 1011 platelets/concentrate. The ‘CS-3000 Omnix’ is significantly more effective in separating (58.4 ± 15.5%) than the ‘AS-104’ with 44.2 ± 7.2% (p < 0.0001). Conclusions: Since both donor groups were comparable regarding all factors recorded – especially the cardiovascular risk factors – the separation process could be responsible for the different traumatisation of platelets.

In the present study we investigated the contrast medium flow in 8 different types of left heart catheter having two different diameters (each n = 5). Using a 10 ml syringe and the contrast medium Ultravist 370, we calculated a mean value of 94.24 N + 16.01 for the maximum manual injection force in 18 test subjects. For the sake of simplicity, the figure of 100 N was defined as standardized manual force (which is within the standard deviation). If the maximally admissible static pressure of 82.5 bar is not to be exceeded, flow rates of not more than 16-17 ml/s are possible with 5.2 Fr. catheters, and 21-23 ml/s and 1.46 ml/s for 5.2 Fr. catheters, and between 1.99 ml/s and 2.17 ml/s for 6 Fr. catheters. Thus, a 50% higher flow can be achieved with 6 Fr. catheters as compared with 5.2 Fr. catheters at the same injection force. The iodine delivery rates are between 506 mg iodine/s and 539 mg iodine/s for 5.2 Fr. catheters, and between 738 mg iodine/s and 804 mg iodine/s for 6 Fr. catheters. The figures for the jet stream.

Poly(ether imide) (PEI) is being explored as potential biomaterial for cardiovascular applications. Different studies showed that human umbilical venous endothelial cells (HUVEC) are able to adhere and proliferate on PEI membranes (R(q) = 13.20 ± 1.58 nm). A recently published study revealed evidence for much lower platelet adhesion on very smooth PEI-films (R(q) = 2.37 ± 1.40 nm). Therefore, we explored whether primary human venous endothelial cells (HUVEC) are able to adhere and proliferate on such very smooth PEI-films compared to tissue-cultured polystyrene (TCP) as reference material. Cytotoxicity testing revealed that PEI had a slight cytotoxic effect on HUVEC accompanied by a marginal reduced integrity of the plasma membrane and a significant lower mitochondrial activity. However long-term seeding experiments up to eleven days exhibited that HUVEC were able to proliferate on the PEI-films till confluence (TCP 96,190 ± 18,289 cells/cm(2); PEI 91,590 ± 19,583 cells/cm(2)). Further studies are planned to monitor the influence of shear force on the endothelial cell monolayer in a dynamic test system to determine its stability in view of shear resistant endothelialization of PEI for cardiovascular devices.

A dataset of 439 confocal laser scanning microscopic images was analyzed to investigate the potential of an image-based automated analysis for identifying and assessing adherent thrombocytes on polymer surfaces. Parameters for image optimization of glutardialdehyde induced fluorescence images were classified and data mining was performed using the Java image processing software ImageJ. Previously reported analysis required that each thrombocyte had to be identified interactively and outlined manually. Now, we were able to determine the number and area of adherent thrombocytes with high accuracy (spearman correlation coefficient r = 0.98 and r = 0.99) using a two-stage filter-set, including a rolling ball background subtraction- and a watershed segmentation-algorithm. Furthermore, we could proof a significant correlation between these parameters (spearman correlation coefficient r = 0.97), determining both as suitable predictors for the evaluation of material induced thrombogenicity. The here reported image-based automated analysis can be successfully applied to identify and measure adherent thrombocytes on polymer surfaces and, thus, might be successfully integrated in a high-throughput screening process to evaluate biomaterial hemocompatibility.

For the successful clinical and biological application of polymers, their interaction with cells, tissues, and body fluids has to be well characterized. In order to investigate how the physical, chemical, and mechanical properties of candidate biomaterials influence cell behaviours, the testing sample is usually placed in commercially available cell culture plates. Thus, not only the testing sample itself but also the culture dish material might influence the cell behaviour. Therefore, an insert system was created to exclude this influence and allow investigations of the testing material solely. In this study micropatterned inserts prepared from polystyrene (PS) as well as from poly(ether imide) (PEI) with three different roughness levels of i) Rq = 0.29 μm (PS) and 0.23 μm (PEI); ii) Rq = 3.47 μm (PS) and 3.92 μm (PEI); and iii) Rq = 22.16 μm [corrected] (PS) and 22.65 μm (PEI) were explored with regard of their immuno-compatibility including the determination of potential contaminations with endotoxins or other microbial products. The endotoxin levels of the inserts were determined to be less than 0.07 EU/mL, which is well below the U.S. Food and Drug Administration limit of 0.5 EU/mL and the survival of murine macrophages cultured in the inserts was not impaired. Activation of early immune mechanisms such as complement activation and the generation of reactive oxygen species could not be observed. All tested materials had no influence on the cytokine secretion from cells of whole human blood. The investigated inserts were immuno-compatible and apparently free of contaminations with microbial products. The roughness of the inserts had no stimulatory or inhibitory effect on early immune mechanisms. Conclusively, the 24-well plate insert systems introduced in this study allow investigating the interactions of tailored surface properties such as roughness with many other cell types, without the disadvantage of the standard commercially available culture vessels influencing the biomaterial testing.

Stent thrombosis and restenosis after drug-eluting stent (DES) implantation remains a relevant problem in the cardiovascular field. The polymer-based biomaterial (e.g. stent coating) requirements are comprehensive, since the polymeric material ideally should ensure an effective re-endothelialization by recruiting endothelial cells (EC) and endothelial progenitor cells (EPC). Simultaneously, the polymer should effectively prevent adherence of smooth muscle cells (SMC) and thereby inhibiting restenosis. The aim of this study was to gain a basic understanding on the interaction of SMC and human umbilical vein endothelial cells (HUVEC) with nonporous polymer films. A multifunctional copolyetheresterurethane (PDC) was chosen as candidate material: PDC consists of poly(p-dioxanone) (PPDO) and poly(e-caprolactone)-segments (PCL). In our study it was compared to the degradable PPDO homopolymer and poly(vinylidene fluoride-co-hexafluoropropene) (PVDF), an established coating material of DES in clinical applications intended for longterm applications. The films were analyzed according to their thermomechanical and surface properties before being examined in contact with HUVEC and SMC concerning cell viability, proliferation and adhesion. Experimental results showed that adhesion could be improved for HUVEC on PDC compared to PPDO and PVDF. In contrast, SMC attachment is largely suppressed on PDC polymeric films indicating a cell-specific response of HUVEC towards PDC. In conclusion, PDC represents a promising candidate material for future cardiovascular applications like e.g. biodegradable (PDC) stent coatings.

Epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 (CYP)-dependent epoxidation of arachidonic acid (AA) inhibit thrombocyte adhesion to the vascular wall. Upon dietary omega-3 fatty acid supplementation, EETs are partially replaced by eicosapentaenoic acid (EPA)-derived epoxyeicosatetraenoic acids (EEQs) and docosahexaenoic acid (DHA)-derived epoxydocosapentaenoic acids (EDPs). We hypothesized that the omega-3 epoxy-metabolites may exhibit superior anti-thrombogenic properties compared to their AA-derived counterparts. To test this hypothesis, we analyzed the effects of 11,12-EET, 17,18-EEQ and 19,20-EDP on Ristocetin-induced thrombocyte aggregation (RITA), a process that mimics thrombocyte adhesion to the vascular wall. The eicosanoids were added for 5, 30, or 60 minutes to thrombocyte-rich plasma freshly prepared immediately after blood collection from stringently selected apparently healthy subjects. Thrombocyte aggregation was then induced by Ristocetin (0.75 mg/mL) and assessed by turbidimetric measurements. After 60 minutes of preincubation, all three epoxy-metabolites significantly decreased the rate of RITA. 17,18-EEQ and 19,20-EDP were effective already at 1 μM, whereas 5-fold higher concentrations were required with 11,12-EET. Addition of AUDA, an inhibitor of the soluble epoxide hydrolase, potentiated the effect of 17,18-EEQ resulting in a significant further decrease of the velocity as well as amplitude of the aggregation process. In contrast to their profound effects on RITA, none of the epoxy-metabolites was effective in reducing collagen- or ADP-induced thrombocyte aggregation. These results indicate a highly specific role of CYP-eicosanoids in preventing thromboembolic events and suggest that the formation of 17,18-EEQ and 19,20-EDP may contribute to the anti-thrombotic effects of omega-3 fatty acids.

BACKGROUND The patency of small-diameter vascular prostheses is limited by several factors such as thrombogenicity, which is strongly influenced by surface roughness and chemical composition, or a mechanical mismatch between the elastic modulus of an artery and of the vascular prosthesis. A confluent layer of endothelial cells onto the inner surface of vascular prostheses could improve the hemocompatibility of the device. Biomaterials with adjustable elastic properties could be tailored to the values of human arteries so that a prothesis mismatch could be avoided. It was recently demonstrated that a co-culture of endothelial cells with angiogenically stimulated monocytes (aMO2) shows an accelerated formation of a functional confluent endothelial cell monolayer on soft hydrophobic poly(n-butyl acrylate) (cPnBA) networks. In addition, the cell compatibility with vascular smooth muscle cells and aortic fibroblasts, which are other important cell types of the vessel wall, is essential for a vascular prosthesis material and must therefore be explored. PURPOSE Here we investigated the interaction of human vascular smooth muscle cells and aortic fibroblasts with cPnBA04 and cPnBA73. MATERIAL AND METHODS Human primary vascular smooth muscle cells and aortic fibroblasts were seeded on the two cPnBAs with different elastic moduli (cPnBA04 - 250 kPa and cPnBA73 - 1100 kPa) over 72 h. A live-dead staining (fluorescein diacetate/propium iodide) was performed to determine the morphology and viability of adherent cells. Furthermore, the extracellular matrix components, the actin cytoskeleton, the cell-material-contacts and the cytokine profiles were analysed. RESULTS Both cell types adhered and were viable on cPnBA04 and cPnBA73. The level of pro-inflammatory cytokine secretion (IFN-γ and TNF-α) by smooth muscle cells and vascular fibroblasts was comparable to that of cells cultivated on a control material. The release of these cytokines by human fibroblasts was higher on cPnBA73 compared to cPnBA04. Both cell types secreted an extracellular matrix comparable to cells seeded on a control material. CONCLUSION The study revealed, that cPnBA with varying elastic moduli are not only suitable for the cultivation of endothelial cells, but also for human vascular smooth muscle cells and aortic fibroblasts. Therefore, cPnBA could be a potential candidate material for the development of cardiovascular prostheses.

Contrast media-induced nephropathy (CIN) is a known complication of intra-arterial application of radiographic contrast media (RCM) and is associated with both short- and long-term outcomes. The development of CIN is not easy to diagnose due to a lack of a uniform definition of CIN. CIN was reported in 4 to 20% of patients after intra-arterial RCM administration during coronary angiography. An all-cause mortality rate of CIN patients amounted to 9% compared with 2% among patients not developing CIN. Pre-existing chronic renal insufficiency, especially, was described as important factor predisposing for CIN, but there was recent clinical evidence that CIN may occur also in low risk ambulatory patients, probably depending on the type of RCM used. Strongly depending on the type of RCM administered there were marked differences in the morphological changes of erythrocytes as well as endothelial cells coinciding in some cases with microcirculatory disorders in patients as well as in animal models. Iodixanol brought about the least cellular and microcirculatory effects while Iopromide induced the strongest disturbances in capillary perfusion and myocardial oxygen tension. It is unclear, however, whether this favours the development of CIN.

BACKGROUND: The protective effect of acetylsalicylic acid (aspirin) in primary and secondary prophylaxis of cardiovascular events is attributed to the inhibition of platelet cyclooxygenase (COX). However, a recent animal study found a vasodilating and blood pressure lowering effect of aspirin independent of COX, but mediated by inhibition of the RhoA/Rho kinase signaling pathway. METHOD: Prospective, randomized, double-blind, placebo-controlled cross-over study. In each instance 5 healthy volunteers received either aspirin 500 mg/d or placebo for 7 days. Capillary red blood cell velocity (vRBC) at rest and after postischemic hyperemia was determined on day 1 and 7 by means of nailfold capillary microscopy. RESULTS: In the aspirin group after 7 days a significant increase of vRBC was found at rest and during hyperemia. In the placebo group vRBC did not change. The finding was confirmed by the cross-over design of the study. CONCLUSION: Aspirin at a dosage of 500 mg/d has an impact on vasoregulation in the microcirculation. At present, the underlying mode of action in humans is unknown.

Gelatins functionalized with desaminotyrosine or desaminotyrosyl tyrosine form physically crosslinked polymer networks due to the interactions between the introduced aromatic moeties. In the swollen state, their mechanical properties can be tailored in a range similar to the elasticity of soft tissues. The aim of this study was to evaluate their potential as biomaterials by determining whether these materials - in comparison to plain gelatin - induce bleedings, thrombotic processes, or angiogenesis. These investigations were performed using the hen's egg chorioallantoic membrane (HETCAM) assay. These results indicate that the gelatin-based hydrogels did not possess angiogenic effects and also did not induce bleedings, thrombotic processes or vessel destruction (avascular zones). The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (1 hour up to several days).

After intra-arterial administration of several radiographic contrast media (RCM) a disorder of the downstream microcirculation with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure in the myocardium of the pig heart was described. Iodixanol did not induce such a microcirculatory disorder in the myocardium of the beating heart of pigs. Whether the morphological changes reported in venous endothelial cells after incubation in culture media supplemented with RCM in vitro coincide with a serious endothelial cell dysfunction is not known. In this study we wanted to get information on possible states of dysfunction or perturbation of venous and arterial ECs through the release of prostacyclin, which was shown to follow the perturbation of ECs. Functionally confluent venous endothelial cells on extracellular matrix secreted great amounts of prostacyclin in reaction to the RCMs indicating a clear perturbation of the ECs. This was not the case in arterial EC cultures. The prostacyclin release from arterial ECs exposed to Iodixanol was more than 10-fold higher than that from arterial ECs exposed to Iomeprol. This could be one of the important factors contributing to the undisturbed myocardial microcirculation after injection of Iodixanol despite a slight echinocyte formation.

The need for engineered devices to treat cardiovascular diseases is increasing due to an aging population and a changing lifestyle. Soft poly(n-butyl acrylate) (cPnBA) networks were recently described as polymer networks with adjustable mechanical properties and suggested as soft substrates for cells, which could potentially be used for cardiovascular implants. Vascular prostheses designed to be implanted in arteries should have an elasticity similar to blood vessels (elastic modulus at body temperature between 100 and 1200 kPa). Therefore, cPnBA networks with E-moduli of 250 kPa (cPnBA0250) and 1100 kPa (cPnBA1100) were developed. Recently, it was shown that both materials were non-cytotoxic for murin fibroblasts, human primary endothelial cells and human monocytes. However, before such newly developed polymers can be used in vivo, it has to be assured that the sterilized materials have a very low endotoxin load to avoid an unspecific activation of the immune system, which otherwise might cause local or systemic inflammatory responses and could lead to severe pathologies. In this study we investigated the immuno-compatibility of sterilized cPnBA0250 and cPnBA1100 with the help of an immuno-competent macrophage cell line as well as with whole human blood.

The cell population of peripheral blood monocytes/macrophages (MO) is heterogeneous: The majority of the MO are CD14++ CD16- and named "classical" (= MO1). Furthermore, two other subpopulations were described: CD14++ CD16+ ("intermediate" = MO2) and CD14+ CD16++ ("non-classical" = MO3). It is reported that MO2 possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic neutrally charged acrylamide-based hydrogel human intermediate (CD14++ CD16+ ), angiogenically stimulated CD163++ monocytes/macrophages (aMO2) maintained a proangiogenic and noninflammatory status for at least 14 days. Here, we explored whether this aMO2 subset adhered to hydrophobic poly(n-butyl acrylate) networks (cPnBA) and also remained in its proangiogenic and noninflammatory status. Because substrate elasticity can impact adherence, morphology, and function of cells, cPnBAs with different Young's modulus (250 and 1100 kPa) were investigated, whereby their elasticity was tailored by variation of the cross-linker content and matched to the elasticity of human arteries. The cPnBAs exhibited similar surface properties (e.g., surface roughness), which were maintained after ethylene oxide sterilization and exposure in serum-free cell culture medium for 18 h at 37°C. aMO2 were seeded on cPnBA samples (1.7 × 10(5) cells/1.33 cm(2) ) in Dulbecco's modified Eagle medium (DMEM high glucose) supplemented with vascular endothelial growth factor 165 (VEGF-A(165) , 10 ng/mL) and fetal calf serum (10 vol%) for 3 and 72 h. On both polymeric samples (n = 3 each), the numbers of adherent cells per unit area were significantly higher (P 0.01; cPnBA0250: 3 h 13 ± 5 cells/mm(2) , 72 h 234 ± 106 cells/mm(2) ; cPnBA1100: 3 h 14 ± 3 cells/mm(2) , 72 h 198 ± 113 cells/mm(2) ) compared to control cultures (glass, 3 h: 6 ± 3 cells/mm(2) , 72 h: 130 ± 83 cells/mm(2) ) and showed a typically spread morphology. The mRNA expression profile of the aMO2 was not influenced by the substrate elasticity. In the supernatant of aMO2 on cPnBA0250, significantly less VEGF-A(165) product was found than expected based on the mRNA level measured (P 0.01). Tests with recombinant VEGF-A(165) then demonstrated that significantly more VEGF-A(165) was adhered on cPnBA0250 than on cPnBA1100 (P 0.01). Seeded on cPnBA, aMO2-unaffected by the elastic moduli of both substrates-seemed to remain in their subset status and secreted VEGF-A(165) without release of proinflammatory cytokines. These in vitro results might indicate that this MO subset can be used as cellular delivery system for proangiogenic and noninflammatory mediators to support the endothelialization of cPnBA.

So called intermediate (MO2) monocytes/macrophages possess anti-inflammatory properties and express the MO lineage marker CD163. On a hydrophilic, acrylamide-based hydrogel human intermediate (CD14++ CD16+) CD163++ monocytes/macrophages (aMO2) which were angiogenically stimulated, maintained a pro-angiogenic and non-inflammatory status for at least 14 days. Here we explored, whether this aMO2 subset can positively influence the proliferation of human umbilical venous endothelial cells (HUVECs) without switching back into a pro-inflammatory (MO1) phenotype. aMO2 or HUVEC were seeded alone on glass cover slips (0.5 × 10(5) cells / 1.33 cm(2)) in a HUVEC specific cell culture medium (EGM-2) for 3 hrs, 24 hrs and 72 hrs or under co-culture conditions (0.5 × 10(5) HUVEC + 0.25 × 10(5) aMO2 / 1.33 cm(2)) in EGM-2 for the same time window as well (n = 6 each). Under co-culture conditions the numbers of adherent HUVEC per unit area were significantly higher (p < 0.01; 525 ± 52 HUVEC/mm(2)) compared to control mono-cultures (473 ± 76 HUVEC/mm(2)) after 72 hrs of cultivation and showed their typically spread morphology. The aMO2 remained in their subset status and secreted VEGF-A165 without release of pro-inflammatory cytokines until the end of the 72 hrs cultivation time period, thereby supporting the HUVEC proliferation. These in vitro results might indicate that this MO subset can be used as cellular delivery system for pro-angiogenic and non-inflammatory mediators to support the endothelialisation of biomaterials like e.g. cPnBA.

Small calibre vascular prostheses (

Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into a variety of cell types. Therefore, they are widely explored in regenerative medicine. The interaction of MSCs with biomaterials is of great importance for cell proliferation, differentiation and function, and can be strongly influenced by numerous factors, such as the chemical nature and the mechanical properties of the material surface. In this study, we investigated the interaction of bone marrow derived human MSCs with different amorphous and transparent polymers namely polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), polyetherurethane (PEU) and poly(styrene-co-acrylonitrile) (PSAN). To ensure that the MSCs were solely in contact to the testing material we applied polymeric inserts, which were prepared from the aforementioned polymers via injection molding. The explored inserts exhibited a similar wettability with advancing contact angles ranging from 84 ± 7° (PEU) to 99 ± 5° (PS) and a surface roughness of Rq ≤ 0.86 μm. The micromechanical properties determined by AFM indentation varied from 6 ± 1 GPa (PEU) to 24 ± 5 GPa (PSAN). Cells presented different adhesion rates on the polymer surfaces 24 hours after seeding (45 ± 7% (PS), 63 ± 1% (PC), 75 ± 4% (PEI), 69 ± 2% (PEU) and 61 ± 5% (PSAN)). The cells could proliferate on the polymer surfaces, and the fold change of cell number after 16 days of culture reached to 1.93 ± 0.07 (PS), 3.38 ± 0.11 (PC), 3.65 ± 0.04 (PEI), 2.24 ± 0.15 (PEU) and 3.36 ± 0.09 (PSAN). Differences in cell apoptosis could be observed during the culture. After 7 days, the apoptosis of cells on PC, PEI and PSAN decreased to a level comparable to that on standard tissue culture plate (TCP). All of the tested polymers exhibited low cytotoxicity and allowed high cell viability. Compared to cells on TCP, cells on PC and PEI showed similar morphology, distribution as well as F-actin cytoskeleton organization, whereas cells on PSAN were distributed less evenly and cells on PEU were less oriented. Cells were more likely to form clusters on PS. Conclusively, we demonstrated the influence of polymer substrates on the cellular behaviour of MSCs, which could be included in the development of novel design concepts based on polymeric biomaterials.

As the majority of the polymers used as cardiovascular grafts so far do not match the elasticity of human arteries (100-1000kPa) and the required endothelialization, a multifunctional material approach is needed to allow the adjustment of the mechanical properties while at the same time exhibiting a haemocompatible surface. Recently soft poly(n-butyl acrylate) networks (cPnBA) with adjustable mechanical properties were introduced as candidate materials with a surface that can be endothelialized. In this study, angiogenically stimulated intermediate CD163(+) monocytes/macrophages (aMO2) were utilized as a cellular cytokine release system to realize the functional endothelialization of the hydrophobic cPnBA surface. We investigated the influence of co-cultured aMO2 on the morphology, density and cytokine secretion of human umbilical venous endothelial cells (HUVEC) seeded on cPnBA with an elastic modulus of around 250kPa (cPnBA0250). A functional confluent HUVEC monolayer could be developed in the co-culture within 3days. In contrast, the HUVEC in the monoculture exhibited stress fibres, broadened marginal filament bands and significantly more and larger cell-free areas in the monolayer, indicating incomplete cell-substrate binding. Remarkably, a functional confluent monolayer formation could only be achieved in co-cultures; it did not develop with the sole supplementation of recombinant VEGF-A(165) to the HUVEC monocultures (unpublished data). The study demonstrated the multifunctional potential of cPnBA in combination with aMO2 as a cellular cytokine release system, adapting their secretion to the demand of HUVEC. In this way, a functional confluent monolayer could be generated within 3days.

Biomimetic polymer network systems with tailorable properties based on biopolymers represent a class of degradable hydrogels that provides sequences for protein adsorption and cell adhesion. Such materials show potential for in vitro MSC proliferation as well as in vivo applications and were obtained by crosslinking different concentrations of gelatin using varying amounts of ethyl lysine diisocyanate in the presence of a surfactant in pH 7.4 PBS solution. Material extracts, which were tested for cytotoxic effects using L929 mouse fibroblasts, were non-toxic. The hydrogels were seeded with human bone marrow-derived MSCs and supported viable MSCs for the incubation time of 9 d. Preadsorption of fibronectin on materials improved this biofunctionality.

Background: Coronary (micro)vascular resistance is regulated by the complex interplay of several factors. Two potentially important determinants include endothelial function and the rheological properties of blood. However, their impact on the control of the coronary resistance vasculature is poorly understood. Methods: The corrected Thrombolysis In Myocardial Infarction frame count (TIMIfc, an index of coronary flow velocity), conduit artery endothelial function, intima-media thickness of the common carotid artery and complete blood counts were measured in 145 patients undergoing elective coronary angiography. Patients with obstructive coronary artery disease or systemic conditions thought to be associated with microvascular disease were excluded from the analysis. Results: There was a strong correlation between the TIMIfc measured in the three main coronary artery distributions (R values between 0.71 and 0.85, P < 0.00001). The TIMIfc was higher in males (P < 0.05), but there was no association with traditional risk factors for coronary artery disease (all P > 0.1). There was a correlation between TIMIfc and L-FMC, a parameter of resting endothelial function (R = 0.33, P < 0.0005). TIMIfc also correlated with mean platelet volume (a marker of platelet activation, R = 0.33, P < 0.001), and hematocrit (R = 0.33, P = 0.0002). There was no correlation between TIMIfc and carotid intima-media thickness and the degree of coronary atherosclerosis. Logistic regression analysis showed that L-FMC and hemorheological variables may explain as much as 19% of the variability in TIMIfc. Conclusions: Resting peripheral endothelial function, as well as parameters of platelet function, correlate with coronary TIMIfc. These data emphasize the existence of an association between endothelial function, hemorheological variables and coronary blood flow velocity.

Ziel: Prüfung des Einflusses des C2/C6-Besetzungsverhältnisses und des Substitutionsgrades von zwei 6%igen Hydroxyäthylstärke-(HES-)Lösungen auf die Eliminationskinetik und die Fluidität des Blutes. Design: Einfach-blinde prospektive randomisierte Cross-over-Studie. Rahmen: Hämostaseologisch-angiologische Ambulanz der Universitätsklinik Homburg. Teilnehmer: 6 freiwillige, klinisch unauffällige Probanden. Interventionen: Es wurde jeweils eine Infusion von 500 ml zweier verschiedener HES-Lösungen (6% HES 200/0,5 bzw. 6% HES 200/0,62) intravenös innerhalb von einer Stunde verabreicht. Zwischen den beiden Infusionen wurde eine Auswasch-phase von 3 Monaten eingehalten. Gemessen wurden Konzentration und Moleku-largewichtsverteilung der intravasalen HES-Moleküle bis zu 24 h nach Infusion so-wie die Fluidität des Blutes vor und nach Infusion. Ergebnisse: Neben der molaren Substitution (MS), die für die beiden eingesetzten HES-Lösungen unterschiedlich ist, beeinflußt das Besetzungsverhältnis der C2- bzw. C6-Atome (C2/C6-Besetzungsverhältnis) am Glukosering den Abbau der HES-Moleküle. Die entstehenden Degradationsprodukte haben bei hohem C2/C6-Beset-zungsverhältnis und hoher MS ein im Mittel höheres Molekulargewicht. Dies beeinflußt die Fließfähigkeit des Blutes. Während die Hämatokritabnahme eine Stunde nach Infusionsende vergleichbar ist, bleibt die Hämatokriterniedrigung bei hohem C2/C6-Besetzungsverhältnis und hoher MS länger erhalten. Der Plasmaviskositäts-anstieg ist bei hohem C2/C6-Besetzungsverhältnis und hoher MS starker ausgeprägt. Schlußfolgerungen: Die Infusion von HES 200/0,62 führt zu einer wesentlich längeren Verweildauer im Vergleich zu HES 200/0,5, verbunden mit deutlich größeren Degradationsprodukten im Plasma, was einen stärkeren Verdünnungseffekt, aber auch einen stärkeren Anstieg der Plasmaviskosität bis zu 24 h nach Infusionsende bewirkt. Bei der Hämodilutionsbehandlung von Patienten mit arterieller Verschlußkrankheit wird der Einsatz von HES, die einen Plasmaviskositätsanstieg induziert, eher als unwillkommen diskutiert.

The aim of this investigation was to examine the effect of felodipine on the blood pressure and on the rheological properties of patients who suffer from arterial hypertension without secondary organic changes (WHO stage I) and had not undergone antihypertensive treatment up to that time. 104 patients were included in this randomised, placebo-controlled double-blind study. Felodipine significantly decreased the confirmatory parameters, the systolic and diastolic blood pressures, by 10% from 154 to 140 mmHg and from 94 to 85 mmHg respectively (p

Biopolymer-based systems with adjustable macroscopic properties that can be varied in a wide range using only small changes in chemical composition are promising candidates for biomaterial-induced autoregeneration. Glycidylmethacrylated gelatin is photopolymerized with the addition of PEG mono- or dimethacrylate to form co-networks in pH = 7.4 PBS. The degree of swelling (Q) and water uptake (H) in PBS at 37 °C are tailorable for PEGDMA co-networks (Q ≈ 250-650 vol%), while the storage modulus of swollen networks at 3 °C can be adjusted by the PEG(D)MA content (G' = 0.7-145 kPa). Indirect cytotoxicity tests on ethylene oxide sterilized films show non-toxic responses for the homonetwork and all but one PEGDMA-containing co-networks materials.

Injection of labeled microspheres is an established method in animal models to analyze the capillary organ blood flow at different time points. However, the microspheres can lead to stenoses of the capillary lumen, which might affect tissue oxygen supply. Our study aimed to investigate the influence of repeated injections of microspheres into the left coronary artery on the tissue oxygen partial pressure (pO2) in the downstream supplied myocardium of Gottingen minipigs. Tests (n = 6 pigs each) were performed with two differently sized microspheres (o = 10 ± 0.1 μm (M10) or o = 15 ± 0.15 μm (M15)) from polystyrene. The pO2 was measured in the midmyocardium of the left and right ventricle for 6 min continuously after each of five injections (1 × 106 microspheres each). There was a time laps of 12 min between each injection. In addition, the influence of the carrier solution was analyzed solely in the identical time frame. pO2 decreased significantly in the myocardial area supplied by the ramus interventricularis paraconalis after injection of M15 microspheres. In contrast, the application of the M10 microspheres did not change the myocardial pO2. This finding suggests to use microspheres with diameters not exceeding 10 μm for the coronary blood flow assessment.

One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role.

ZusammenfassungEs werden die Wirkungen von Knoblauch auf Theologische und hämostaseologische Variablen, Lipide und den Blutdruck sowohl aus eigenen Untersuchungen als auch aus der Literatur zusammengestellt. Erste deutlich dosisabhängige Effekte werden nach Einmaldosen von 300 mg bzw. Tagesdosen von 600 mg gefunden. Der maximale Wirkzeitpunkt liegt zwischen 4 und 6 Stunden nach der Einnahme. Knoblauch reduziert die spontane und die induzierte Thrombozytenaggregation, die Plasmaviskosität, den Hämatokritwert und läßt die fibrinolytische Aktivität, den Durchmesser präkapillärer Arteriolen und die Mikrozirkulation ansteigen. Eine signifikante lipidsenkende Wirkung ist bislang in kontrollierten klinischen Studien mit 423 Patienten belegt. Milde Blutdrucksenkungen sind in mehreren Untersuchungen beobachtet worden. Bei einer täglichen Dosis von 900 mg treten bei bis zu 25% der Patienten knoblauchbedingt Geruchsbelästigungen auf. Darüber hinaus werden von 5% der Patienten gastrointestinale Beschwerden, bei starker Überdosierung Blutdruckabfälle (in seltenen Fällen bis zum Kollaps) angegeben. Ein Wirksamkeitsnachweis im Sinne einer Antiatherosklerosewirkung liegt bisher nicht vor, eine Gehstrekkensteigerung konnte für die periphere arterielle Verschlußkrankheit in einer Pilotuntersuchung gezeigt werden.

Received 1.7.1992; accepted 16.2.1993) Conjunctival video-capillaroscopy was used to investigate the effect of oral contraceptives on the conjunctival microcirculation of 21 healthy female subjects under normal and post ischemic conditions. The study consisted of an experimental group of ten females using oral contraceptives containing 30 J.lg Ethinyl Estradiol, and a control group of eleven females not using oral contraceptives. Capillary red blood cell velocity was significantly lower (35%; p

Monocytes/macrophages are known to exhibit pro-angiogenic activities after VEGF stimulation. Recently, it was shown that VEGF stimulated macrophages can support growth of microvascular endothelial cells from the lung when both cell types were cocultured using a cell ratio of 1 : 1. However, endothelial cells can have different phenotypic characteristics and metabolism depending on the originating vascular bed and tissues, and only few data have been published regarding the regiospecific sensitivity of microvascular endothelial cells for angiogenic stimuli. Reports about differences in the microvascular bed of the lung and the skin motivated to investigate angiogenic effects of VEGF stimulated macrophages (ma) on the doubling time and the cell growth behaviour of skin derived microvascular endothelial cells (HMVEC/S). During the study period of 60 days, ma supported growth and proliferation of the HMVEC/S, when ma and HMVEC/S were cocultured at a ratio of 0.5 : 1. However, these effects were not seen in a 1 : 1 coculture. This result indicates that there is a positive correlation between the pro-angiogenic effects of ma and the number of endothelial cells in the direct neighbourhood of the ma and also suggests a different sensitivity of microvascular endothelial cells to angiogenic stimuli depending on the tissue from which they were isolated.

The processing of polymers for blood contacting devices can have a major influence on surface properties. In this study, we fabricated poly(ether imide) (PEI) membranes and films to investigate the effects of the processing on physicochemical surface properties by atomic force microscopy (AFM), scanning electron microscopy, contact angle as well as zeta potential measurements. A static platelet adhesion test was performed to analyze the thrombogenicity of both devices. While contact angle measurements showed similar levels of hydrophobicity and zeta potential values were equivalent, mean surface roughness as well as surface energies in the dispersive part were found to be increased for the PEI membrane. The static platelet adhesion test showed a significantly decreased number of adherent platelets per surface area on the PEI film (178.98 ± 102.70/45000 μm 2 ) compared to the PEI membrane (504 ± 314.27/45000 μm 2 ) and, consequently, revealed evidence for higher thrombogenicity of the PEI membrane. This study shows that processing can have a significant effect on platelet adhesion to biomaterials, even though, molar weight was identical. Thrombogenicity of polymer-based cardiovascular devices, therefore, have to be evaluated at the final product level, following the entire processing procedure.

The establishment of a stable endothelial layer on a biomaterial suture is a well known strategy to achieve hemocompatibility. The endothelialisation is supported by factors as e.g. vascular endothelial growth factor (VEGF), which can be secreted by monocytes/macrophages (mo/mΦ) in an angiogenic milieu. In order to avoid detrimental inflammation triggered by these mo/mΦ, we established a protocol for the generation of alternatively activated macrophages and studied their response towards VEGF-A165. We could generate sufficient amounts of these CD14+ CD163+ IL-10+ mo/mΦ from buffy coats(8.6 ± 4.7 × 105 cells/mlbuffy coat). Furthermore, we achieved a VEGF-A165 secretion in the nanogram range. The VEGF-A165 secretion increased 2.1-fold within 14 days from 7.6 ± 2.2 to 16.1 ± 2.5ng/ml when the cells were grown with a VEGF-A165 supplemented (10ng/ml) cell culture medium. Within this time period the secretion levels of other pro-angiogenic growth factors (bFGF, PDGF-BB) and immunomodulatory cytokines (IL-10, IL-12, IL-1ra, TNFα, IFNγ) reached only the picogram range. These results suggest that angiogenically stimulated CD14+ CD163+ IL-10+ mo/mΦ might be useful as a cellular cytokine delivery system supporting endothelialisation of biomaterials without inducing pro-inflammatory effects.

The degradation behavior and the effect on angiogenesis of multiblock copolymers based on poly(p-dioxanone)- and poly(epsilon-caprolactone)-segments (PDC) were studied in vivo. PDC is a multifunctional biomaterial combining degradability and shape-memory capabilities. The "in vivo" degradation of PDC is characterized by a fragmentation occurring at the material tissue interface. This observation is consistent with the enzyme supported degradation behaviour, which was determined "in vitro". PDC revealed to induce the formation of blood micro-vessels nearby in the periimplantary tissues. Both might explain the good PDC integration into tissues in terms of a strong connection between the implant and the periimplantary tissue. Micro blood-vessels might be involved in the clearance of the small particles, which appear in the periimplantary tissue when PDC degrades.

Background: Patients with permanent atrial fibrillation have a clearly higher risk for thromboembolic events than people with sinus rhythm. Because also anticoagulant therapy, which is the therapy of choice in chronic atrial fibrillation, has its risks, intra operative ablation therapy as a concomitant procedure has become more and more important. Nevertheless this option is not available for all patients and little is known whether the operation by its self is able to restore sinus rhythm and about the fate of these patients. Therefore we created a registry to follow the clinical course of patients with atrial fibrillation after heart surgery. Method: All consecutive patients with permanent atrial fibrillationwho were operated in our center and who were not eligible for ablation therapy were included into the registry. The patients were monitored up to postoperative month 12 with regard to their clinical outcome especially rhythm course and survival. These data were evaluated during in-hospital visits 30, 90, 180 and 360 days after operation. Results: A total of 287 (151 male/136 female) consecutive patients with permanent atrial fibrillation were included into the registry. During the follow-up period, approximately 10% of the patients converted to sinus rhythm. 13 patients, or 4.9%, were in stable sinus rhythm, which means that they were in sinus rhythm at every follow-up visit. 30-day mortality was 6.9% (20 of 286 patients) while it was 14.9% after one year (43 of 263 patients). Of the 13 patients who were in stable sinus rhythm after one year, only one patient died (7.7%), while of the 185 patients who where still in atrial fibrillation 43 died (23.2%). Conclusion: Our results demonstrate that also correction of the heart disease by it self is able to restore sinus rhythm in a few patients. Nevertheless the rate of patients with continuous atrial fibrillation was approximately 90%, the rate of stable sinus rhythm, which is suspected to improve prognosis was only 4.9%. Therefore, an attempt to treat atrial fibrillation with intra operative ablation therapy is strongly justified, respecting the fact that, even if conservatively calculated, a success rate of at least 50% can be accomplished. We believe, that this applies even for endocardial and for the epicardial approach. 278 M. Knaut, S. Norkus, S. M. Tugtekin, S. Brose, F. Jung, K. Matschke with intelectual limited capacity without an appropriate social sphere, which in the meantime represent a large portion of patients scheduled for heart surgery [14, 20]. Overdosage poses a risk of hemorrhages [21], whereas underdosage can lead to thromboembolic complications. Additionally, even adequate anticoagulation therapy is not a guarantee of adequate protection [1]. Since only an insufficient amount of data currently exist regarding whether heart surgery alone i.e. bypass and/or valve operations leads to a spontaneous recovery of sinus rhythm, a prospective case study was performed including a sufficiently large group of patients who underwent operations without specific operative antiarrhythmic therapy with preoperative atrial fibrillation. These patients were monitored for up to 12 months postoperatively with regard to rhythm course and survival.

Rheological parameters (hematocrit, plasma viscosity and red blood cell aggregation index), glycosylated hemoglobin (HbAlc) and retinal arteriovenous passagetime (A vP) were measured in 93 patients with type I diabetes. The stage of diabetic retinopathy was graded by means of ophthalmoscopy and video fluorescein angiography. The mean values of hematocrit (men 46 ± 4%, women 43 ± 3 %), RBC aggregation index (13,8 ± 3,8, normals: 14,6 ± 3,2) were equal to normals. Plasma viscosity (1,33 ± 0,09 mPas, normais:l,24 ± 0,05 mPas) was increased. The groups with increasing stage of diabetic retinopathy showed no difference in hematocrit, RBC aggregation and HbAlc and an increase of plasma viscosity. In patients with bad glycemic control plasma viscosity was increased and RBC aggregation index was similar as compared with patients with good glycemic control. If retinal arteriovenous passagetime was worse plasma viscosity and RBC aggregation were more increased. This indicates, that alterated plasma viscosity and RBC aggregation may be one of the reasons for disturbed microcirculation and fundus changes ill diabetic retinopathy.

Most polymers used in clinical applications today are materials that have been developed originally for application areas other than biomedicine. Testing the cell- and tissue-compatibility of novel materials in vitro and in vivo is of key importance for the approval of medical devices and is regulated according to the Council Directive 93/42/EEC of the European communities concerning medical devices. In the standardized testing methods the testing sample is placed in commercially available cell culture plates, which are often made from polystyrene. Thus not only the testing sample itself influences cell behavior but also the culture vessel material. In order to exclude this influence, a new system for cell testing will be presented allowing a more precise and systematic investigation by preparing tailored inserts which are made of the testing material. Inserts prepared from polystyrene, polycarbonate and poly(ether imide) were tested for their cytotoxity and cell adherence. Furthermore a proof of principle concerning the preparation of inserts with a membrane-like surface structure and its surface modification was established. Physicochemical investigations revealed a similar morphology and showed to be very similar to the findings to analogous preparations and modifications of flat-sheet membranes.

In more than 90% of patients with atrial fibrillation (AF), stroke is due to thrombotic embolization from the left atrial appendage (LAA). Transcatheter occlusion with percutaneous left atrial appendage transcatheter occlusion (PLAATO), a self-expanding, membrane- covered spherical nitinol cage, is feasible and an alternative to anticoagulation therapy.This was a single-center prospective registry study for verification of stroke risk reduction in patients with AF 2 years after PLAATO.Seventy-three patients with AF (permanent 65, paroxysmal 8) in whom anticoagulation therapy was contraindicated or rejected underwent transcatheter LAA occlusion with PLAATO. One patient died periprocedurally due to implant embolization, and 1 patient underwent open-heart surgery because of implant instability. The remaining 71 patients were followed for 24 months. In 52 patients a stable anchoring of the PLAATO device without migration or dislocation was documented by transesophageal echocardiography (TEE). No thrombotic deposition was found on the LA luminal surface of the device. Statistically, in our patient cohort, 7 strokes would have been expected without any treatment within 24 months. In fact, no strokes were reported. Ten out of 71 patients died during follow up: 6 in our hospital and 4 at home. None of them died from a stroke.Ninety-seven percent of AF patients were successfully treated with PLAATO. After mechanical LAA occlusion, the 2-year risk of stroke in AF patients is markedly reduced. Therefore, this therapeutic concept is a clear alternative for patients with AF and contraindications for oral anticoagulation.

Background: Oral anticoagulants are routinely used for prevention of thromboembolism in cardiac, arterial or venous diseases. Hemorrhages are serious treatment complications, frequently occurring under long-term and/or high-dose regiments. From animal experiments it is known that coumarin-type anticoagulants may cause capillary dilatation and increased perme- ability, red blood cell extravasation and punctate bleeding. Controlled human trials are lacking. Methods: 31 patients under oral anticoagulation were examined by video capillary microscopy. 52 patients with comparable diseases and treatment but without oral anticoagulation served as controls. Nailfold capillaries of four fingers of each hand were examined and analyzed off-line according to the following criteria: (1) numbers of capillaries investigated, (2) numbers of capillary bleedings, and (3) bleeding incidence (bleedings per 100 capillaries). Results: In 23 out of 31 patients (74.2%) capillary bleedings were observed. The bleeding incidence ranged from 0.33 to 4.29 per 100 capillaries. In contrast, only 4 out of 52 controls were detected with capillary bleedings (2.1%, p< 0.001). The bleeding incidence was 0.34-2.41. In patients on anticoagulation there was no correlation between the number of capillary bleedings and the INR or Quick values. During a two year follow-up of patients on oral anticoagulation no significant difference was found in terms of clinically obvious bleedings in patients with or without capillary bleedings. Conclusion: This study shows that capillary bleedings can be demonstrated in patients on oral anticoagulation. Bleedings occur independent of the INR-value. Thus, other factors than the vitamin-k-dependent coagulation effect seem to be causal for the damage of microvessels. Further, the evidence of capillary bleedings is not a prognostic indicator for future hemorrhage.

A variety of medical grade polymeric materials are used in tissue engineering and biomedical technology. Dense non-porous polymeric foils were used as substrates for endothelial cell layers. Half a the test samples (polymers and control materials) were seeded with bovine corneal endothelial cells (BCEC) which more or less covered the substrates with an extracellular matrix (ECM) in the consecutive culturing period. Afterwards the ECM covered as well as the uncovered materials were seeded with human umbilical venous endothelial cells (HUVEC). HUVEC seeded samples were cultured either under static or under dynamical conditions in a cone/plate rheometer with a mean low arterial shear stress of 8.2 dyn/cm 2 to simulate the flow conditions in a coronary vein graft. With the exemption of polyvinyl chloride all other materials could be coated with ECM at least partially. Under static conditions the best results with respect to complete coverage with ECM and HUVEC were seen on polyester and polyurethane. Under shear load, however, the complete HUVEC layer together with the ECM detached from the polymer surface within a short time. ECM and HUVEC remained no longer than 43 minutes on anyone of the materials tested. The materials as supplied and tested were clearly not appropriate as implants in contact to the flowing blood.

Besides the desirable effect of roentgen ray absorption radiographic contrast media (RCM) can also have varying adverse effects. Under discussion, as a possible cause, are microcirculatory disorders resulting from morphological alterations in erythrocytes and endothelial cells. Therefore, the contrast media-induced release of vasoactive substances (prostacyclin, endothelin-1, and nitric oxide (NO)) from human endothelial cells (HUVEC) induced by two commercially available RCMs (Iodixanol 320, Iomeprol 350) was tested in a controlled in-vitro study. The results show that RCMs lead to endothelial cell trauma in vitro, which is apparent in the release of prostacyclin and endothelin-1, while NO release was not affected. The endothelin-1 release after incubation with Iodixanol was similar to the release in the control cultures. In comparison, lower endothelin-1 levels were measured in the cultures incubated with Iomeprol at all 3 time points indicating a more significant cell trauma. Prostacyclin release - also an indicator of traumatization of endothelial cells - increased after addition of both contrast agents. The highest release was found after incubation with Iomeprol 350.

The permeability of a material is described by the amount of substances (gases, liquids, particles) passing through pores and/or interstices of the material in a certain time. In medicine and biotechnology the permeability is given usually as the amount of water (ml x cm(-2) x min(-1)) permeating per area and time unit through the material. Vascular prostheses are described e.g. as high porous prostheses (e.g. Dacron: 1500-4000 (ml x cm(-2) x min(-1)) or as low porous prostheses (e.g. ePTFE: 200-1000 (ml x cm(-2) x min(-1)). The permeability of blood capillaries is characterized by the exchange of nutrients, metabolites and breathing gases. Capillary permeability and the transport of the permeates through tissues are the key processes for the supply of organs and tissues where especially the protein transport through tissues is described by diffusive and/or convective terms. The vascular permeability is governed by the permeability of the intimal endothelial cells. The major influence is exerted by the interendothelial binding which can change drastically in a very short time. This is demonstrated by the fast development of interstitial lung oedema in case of septical shock. The permeability is an integral indicator of tissue and organ function. It is possible to assess the permeability of native and engineered tissues precisely with a recently developed system. First results will be shown.

International audience; This document, supported by both the International Society for Clinical Hemorheology and the European Society for Clinical Hemorheology and Microcirculation, proposes new guidelines for hemorheological methods used in experimental and clinical studies. It is based on a similar document entitled: "Guidelines for measurement of blood viscosity and erythrocyte deformability" published in 1986 by the Expert Panel on Blood Rheology of the International Committee for Standardization in Hematology. Recent methods, techniques and instruments, as well as new approaches to interpretation of results, are added to these new guidelines; wide spread adoption should improve comparability between hemorheological laboratories and increase the reliability of rheological tests.

The degradation behavior of biodegradable multiblock copolymers (PDC) containing poly(p-dioxanone) hard segments (PPDO) and crystallizable poly(epsilon-caprolactone) switching segments (PCL) synthesized via co-condensation of two oligomeric macrodiols with an aliphatic diisocyanate as junction unit was explored in in vivo and in vitro experiments. The in vitro experiments for enzymatic degradation resulted that the poly(epsilon-caprolactone) segments are degraded faster, than the poly(p-dioxanone) segments. During degradation the outer layer of the test specimen becomes porous. Finally non-soluble degradation products in form of particles were found at the surface. This observation is in good agreement with the in vivo studies, where the non-soluble degradation products in the periimplantary tissues showed a diameter of 1 – 3 micron.