Clinical Hemorheology and Microcirculation - Volume 48, issue 1-3

Authors: Gori, T. | Jung, F.

Article Type: Other

DOI: 10.3233/CH-2011-1432

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 1-3, 2011

Authors: Gehmert, Sebastian | Gehmert, Sanga | Hidayat, Mulyadi | Sultan, Maitham | Berner, Arne | Klein, Silvan | Zellner, Johannes | Müller, Michael | Prantl, Lukas

Article Type: Research Article

Abstract: Recently, it was shown that mesenchymal stem cells (MSCs) are capable of differentiating into endothelial cells which highlights the potential role of MSCs in neovascularization. In the present study, we investigated the paracrine factors responsible for tube formation in human adipose-tissue derived stem cells (ASCs). Moreover, we analyzed ASC's migration towards PDGF-BB and altered levels of proteins involved in different pathways. Freshly isolated human adipose tissue-derived stem cells were seeded onto wells coated with Matrigel and cultured in endothelial growth medium. Capillary-like tube formation was observed after 18 hours culture. Tube formation was significantly reduced in the presence of antibodies …against platelet-derived growth factor receptor beta (PDGF) or basic fibroblast growth factor (bFGF). Reverse phase proteomic assay (RPPA) was used to interrogate the expression of 139 phosphorylated or native proteins after incubation with PDGF-BB protein for 24 hours. The present data suggest, that freshly isolated ASCs contain a subpopuplation of stem cells that can form capillary like tubes which is dependent on PDGF and bFGF signaling pathway. Furthermore, Migration of human ASCs significantly increased in response to increased concentrations of PDGF-BB. In addition, incubation of ASCs with PDGF-BB altered phosphorylation of several transcription proteins that are widely expressed throughout the hematopoietic system, targeting genes that have been associated with proliferation, anti-apoptosis or differentiation. Show more

Keywords: Angiogenesis, adipose-tissue derived stem cells, PDGF-BB, endothelial differentiation, migration

DOI: 10.3233/CH-2011-1397

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 5-13, 2011

Authors: De Spiegelaere, Ward | Cornillie, Pieter | Van den Broeck, Wim | Plendl, Johanna | Bahramsoltani, Mahtab

Article Type: Research Article

Abstract: Angiopoietins are important growth factors for vascular development and quiescence. They are promising targets for pro- or anti-angiogenic therapies in diverse pathologies, but the mechanisms of the ANGPT/TIE2 system are complex and not well understood. In the present study, the separate and combined effects of angiopoietin 1 and angiopoietin 2 were studied, using a recently developed in vitro angiogenesis model that allows both a quantitative and qualitative evaluation of the angiogenic cascade. This cell culture model was performed with microvascular endothelial cells (ECs) originating from different vascular beds, i.e. dermal ECs and cardiac ECs. In addition, the expression of the …angiopoietins and the receptors, TIE1 and TIE2 was analyzed with RT-qPCR. This study revealed that the angiopoietins provoked a differential response in the two endothelial cultures. Both angiopoietin 1 as well as angiopoietin 2 elicited an angiogenic cascade in the dermal ECs but not in the cardiac ECs. In addition, the RT-qPCR data revealed marked differences in the endogenous expression pattern of these factors, indicating that the origin of endothelial cells might have an important impact on their angiogenic potential. Show more

Keywords: Angiopoietin, TEK, real time RT-PCR, endothelial cells, in vitro angiogenesis

DOI: 10.3233/CH-2011-1393

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 15-27, 2011

Authors: Endres, S. | Hiebl, B. | Hägele, J. | Beltzer, C. | Fuhrmann, R. | Jäger, V. | Almeida, M. | Costa, E. | Santos, C. | Traupe, H. | Jung, E.M. | Prantl, L. | Jung, F. | Wilke, A. | Franke, R.-P.

Article Type: Research Article

Abstract: Cost effective and safely to apply tissue engineered constructs of big volume bone transplants for the reconstruction of critical sized defects (CSD) are still not available. Key problems with synthetic scaffold materials are shrinkage and fast degradation of the scaffolds, a lack of blood supply and nutrition in the central scaffold volume and the absent or the scarce development of bone tissue along the scaffold to bridge the bone defect. The use of composite scaffolds made of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium phosphates (CaP) revealed promising therapeutical options for the regeneration of critical sized bone …defects. In this study interconnectively macroporous PLGA scaffolds loaded with microporous and coated with nanoporous calcium phosphates were either seeded in fixed bed bioreactors with allogenic osteogenically induced mesenchymal stem cells and implanted or implanted unseeded into critical sized femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was excised where the proximal and distal parts of the femur were fixed and stabilized by the use of an eight-hole linear reconstruction plate and secured with three bicortical screws (2.7 mm diameter) on every side of the osteotomy. Aim of the study was if we could find a way to load and coat PLGA scaffolds with CaP so that shrinkage of scaffolds could be avoided, which would favour angiogenesis, blood supply and nutrition in the construct and thus avoid central necroses regularly observed so far in transplants not vascularized and which would be inhabited by cells of he bone lineage forming new bone and healing the defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided and scaffolds were practically not degraded. Both scaffolds, loaded and loaded and coated, revealed blood vessels in all parts of the implants after 4 weeks. Only in scaffolds seeded with allogenic mesenchymal stem cells the development of bridging bone constructs between proximal and distal edges of the femur was observed after four weeks without further supplementation of growth factors. In case of the implantation of non-seeded scaffolds no obvious scaffold bound bone development could be shown. Show more

Keywords: Critical-sized defect, PLGA/CaP, bone marrow, CaP nanoparticles

DOI: 10.3233/CH-2011-1406

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 29-40, 2011

Authors: Franke, R.P. | Fuhrmann, R. | Hiebl, B. | Jung, F.

Article Type: Research Article

Abstract: After intra-arterial administration of radiographic contrast media (RCM), a disorder of the downstream microcirculation both with regard to blood flow velocity in microvessels and to tissue oxygen partial pressure was described. Possible factors contributing to this microcirculatory disorder are increase in plasma viscosity, a formation of echinocytes, a buckling and denudation of endothelial cells, and a disturbation of endothelial prostacyclin release. It is not known so far whether the reactions observed in the context of RCM applications are reactions of venous endothelial cells alone or also of arterial endothelial cells. Therefore, arterial ECs on ECM were exposed to the same …RCMs under identical conditions. The decrease of cell-cell contacts with an increase of denuded subendothelial matrix areas in the functionally confluent endothelial cell layer on ECM were more pronounced after a five minute exposure of endothelial cells to Iomeprol compared to Iodixanol. Changes in arterial ECs after the incubation in culture media supplemented with RCM were very subtle in comparison to changes in venous ECs. Show more

Keywords: Iodixanol, Iomeprol, endothelial cells, morphology

DOI: 10.3233/CH-2011-1404

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 41-56, 2011

Authors: Mayer, A. | Lee, S. | Lendlein, A. | Jung, F. | Hiebl, B.

Article Type: Research Article

Abstract: Cardiovascular implants such as stents or artificial vascular grafts established in clinical application to date are generally designed as long-term implants. An important requirement for the successful application of these devices is the haemocompatibility of their interface to the blood stream, which often is approached by polymeric coatings. Modern therapies are aiming at curative treatments (Regenerative Medicine) by inducing the in vivo formation of a new endothelial layer on the implant surface ensuring an optimal haemocompatibility based on the generated glycocalyx. A promising approach for providing the required biological stimulus is the secretion of pro-angiogenic factors (such as VEGF-A) by …autologous CD14+ monocytes/macrophages (mo/mΦ), which can be induced by previous angiogenic stimulation. While protocols for negative and positive immune-isolation are already established, this study was aimed to evaluate the efficacy of a positive and a negative MACS™ based immune-isolation protocol by analysing the yield, the purity and the activation status of the isolated CD14+ mo/mΦ. Both protocols enabled the isolation of more than 80% (positive isolation) and 86% (negative isolation) CD14+ mo/mΦ representing approximately 1.3 × 107 CD14+ mo/mΦ from 1 ml buffy coat. Less than 10% of these cells were also positive for CD69. Latter is an important selection criterion as CD69 is a marker characteristic for classically activated and catabolic active mo/mΦ which can negatively affect the endothelialisation process. As the negative immune-isolation protocol resulted in a cell fraction meeting the requirements on a pure cell fraction (percentage of contaminating cells < 15%) this isolation method is advantageous although it was more time consuming than the positive isolation protocol. Show more

Keywords: CD14 antigens, CD69 antigens, cell isolation techniques/methods, monocytes, macrophages, endothelialisation

DOI: 10.3233/CH-2011-1395

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 57-63, 2011

Authors: Cicha, Iwona | Urschel, Katharina | Daniel, Werner G. | Garlichs, Christoph D.

Article Type: Research Article

Abstract: Background: Atherosclerotic plaques develop at arterial regions subjected to non-uniform shear stress, and are initiated by increased leukocyte-endothelial interactions. Here we applied the in vitro model of arterial bifurcations to investigate whether telmisartan, an anti-inflammatory angiotensin II receptor blocker with PPAR-gamma activating ability, prevents monocyte recruitment by endothelium. Methods: Human umbilical vein endothelial cells (ECs) were exposed to 18 h non-uniform shear stress in bifurcating flow-through slides, followed by 2 h stimulation with 2.5 ng/mL TNF-alpha. During flow, cells were treated with telmisartan. To study cell adhesion, ECs were perfused with medium containing THP-1 monocytic cells. Adherent THP-1 monocytes were …quantified by light microscopy. Endothelial protein expression was determined by immunofluorescence. Results: Non-uniform shear stress in combination with TNF-alpha dramatically induced monocytic cell recruitment by endothelial cells. In cells treated with telmisartan (0.5–2.5 μmol/L) during exposure to non-uniform shear stress, dose-dependent inhibition of monocytic cell adhesion was observed, with about 45% reduction at 1 μmol/L. This effect was mediated by a significant reduction of endothelial VCAM-1 expression. On the contrary, the induction of E-selectin by TNF-alpha in ECs exposed to non-uniform shear stress was not affected by telmisartan. The inhibitory effect of telmisartan on monocytic cell recruitment and VCAM-1 induction was prevented in the presence of the PPAR-gamma antagonist GW9662. Conclusions: Treatment with telmisartan decreases the TNF-α-induced recruitment of monocytic cells and endothelial expression of VCAM-1 in regions of non-uniform shear stress in vitro. This mechanism can contribute to the beneficial pleiotropic effects of telmisartan in atherosclerosis-prone arterial regions. Show more

DOI: 10.3233/CH-2011-1394

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 65-73, 2011

Authors: Gehmert, S. | Geis, S. | Lamby, P. | Roll, C. | Braumandl, U. | Hidayat, M. | Sultan, M. | Fuechtmeier, B. | Jung, E.M. | Prantl, L.

Article Type: Research Article

Abstract: Objectives: This study was designed to determine if a) hyperbaric oxygen increases the tissue oxygenation of free flaps and b) verification of this effect is possible by using a recently validated and innovative method for two-dimensional pO2 measurement (Luminescence lifetime imaging = LLI). Methods: Six patients with a free parascapular flap transplanted to the lower limb received hyperbaric oxygen (HBOT) therapy. The HBOT regimen consisted of treatment over 90 minutes with 100% O2 (FiO2 1.0) at 240 kPa (Marx-Schema). The transcutaneous oxygen partial pressure (ptc O2 ) was measured over the entire flap with the use of …luminescence lifetime imaging (LLI) before and 30, 60, 120 minutes after treatment. The LLI is based on the oxygen dependent quenching of phosphorescence of the indicator dye platinum (II)-octaethyl-porphyrin implemented in a polystyrene sensor foil. Results: In all six free flaps we could find a significant increase of tissue oxygen over the entire flap in form of increased R-values as well as subsequently calculated absolute ptc O2 values over a period of 120 min after hyperbaric therapy. The ptc O2 values increased significantly from 42.59 ± 1.11 Torr before to 81.14 ± 5.95 Torr after hyperbaric treatment (p < 0.001). Even after 2 hours the ptc O2 values were significantly higher (83.45 ± 13.80 Torr) compared with values prior to HBOT (p < 0.006). Conclusions: The findings of this study demonstrated an increase of oxygen supply over the entire flap after hyperbaric oxygen therapy. Show more

DOI: 10.3233/CH-2011-1389

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 75-79, 2011

Authors: Geis, S. | Prantl, L. | Gehmert, S. | Lamby, P. | Nerlich, M. | Angele, P. | Egger, L. | Jung, E.M.

Article Type: Research Article

Abstract: Background: Free flap transplantation is used more and more frequently in order to cover extensive wound defects. The basic prerequisite for successful flap salvage after flap failure is a short time interval from failure until revision. For this reason many different flap monitoring systems have been tested over the last years. Objective: The aim of the experiment was to detect critical capillary perfusion using contrast enhanced ultrasound. Quantitative analysis should be performed by a special perfusion software (QONTRAST®; Bracco, Italy) appraising digital raw data of contrast enhanced ultrasound (CEUS). Additionally diverse risk factors for free flap transplantation were determined. Methods: …Thirty-one patients were examined after free flap transplantation during the first 72 hours after operation. CEUS was performed with a linear transducer (6–9 MHz, LOGIQ E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue®, Bracco, Italy). Operation and examination were performed by either an experienced plastic surgeon or an experienced ultrasound examiner. Depth dependent capillary perfusion was analysed and quantitative perfusions analysis was performed using the perfusions software QONTRAST® (Bracco, Italy). Eleven revisions had to be performed: 7 due to haematoma and 4 due to superficial necrosis. Results: Reduced capillary perfusion was seen in all 11 complications using CEUS. Significant difference comparing the no complication and the complication group was observed using TTP (time to PEAK) and RBV (regional blood volume) quantitative analysis. Mean RBV was 922.1 ± 150.9 in the no complication and 303.0 ± 53.9 in the complication group (p = 0.001). Mean TTP was 37.6 ± 3.8 in the no complication and 21.3 ± 3.4 in the complication group (p = 0.006). Tendency to higher complication rate was seen in older male patients with vascular or malignant primary disease. Conclusion: In this clinical trial, capillary perfusion after free flap transplantation as well as detection of vascular complications was demonstrated using CEUS. Quantitative perfusions analysis could be performed and flap viability could be assessed easily. Show more

DOI: 10.3233/CH-2011-1396

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 81-94, 2011

Authors: Uller, W. | Jung, E.M. | Hornung, M. | Ross, C. | Jung, W. | Schlitt, H.J. | Stroszczynski, C. | Agha, A.

Article Type: Research Article

Abstract: Purpose: The objective was to characterize the microcirculation of parathyroid adenomas using contrast-enhanced ultrasound (CEUS) and to evaluate if it can be used for diagnosis and localization of pathologic glands. Patients and methods: Thirty patients with primary hyperparathyroidism scheduled for parathyroidectomy were enrolled. Preoperatively, all patients underwent B-Scan sonography, Colour coded Doppler Sonography (CCDS), Power Doppler (PD) and CEUS. The diagnostic confidence concerning B-Scan, CCDS, PD and CEUS was classified into six grades (0: no adenoma; 5: adenoma). Results: Using CEUS, all adenomatous glands showed a typical dynamic microvascularization. B-Scan showed a mean grade of 2.18, CCDS 2.29, PD 2.33, …CEUS 4.29 (6–9 MHz transducer) and 3.52 (6–15 MHz). The differences between CEUS and conventional sonography were all statistically significant (p < 0.05). CEUS noted a sensitivity of 98.4% and specificity of 98.4% for the detection of adenomatous glands. Conclusion: CEUS facilitates the detection and diagnosis of pathologic parathyroid glands due to their typical microvascularization. Show more

Keywords: Primary hyperparathyroidism, contrast-enhanced ultrasound, microvascularization

DOI: 10.3233/CH-2011-1402

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 95-103, 2011

Authors: Lamby, P. | Prantl, L. | Fellner, C. | Geis, S. | Jung, E.M.

Article Type: Research Article

Abstract: Background: The immediate evaluation of microvascular tissue flaps with respect to microcirculation after transplantation is crucial for optimal monitoring and outcome. The purpose of our investigation was to evaluate the clinical value of contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI (ceMRI) for monitoring the integrity of tissue flaps in plastic surgery. Methods: To this end, we investigated 10 patients (47 ± 16 a) between postoperative day 7 and 14 who underwent flap surgery in order to cover tissue defects in various body regions. For CEUS we utilized the GE LOGIQ E9® equipped with a linear transducer (6–9 MHz). After application of …2.4 ml SonoVue®, the tissue perfusion was detected in Low MI-Technique (MI < 0.2). The perfusion curves were quantitatively analyzed using digital video sequences (QONTRAST®, Bracco, Italy) regarding peak % and relative blood flow (RBF). Furthermore, we investigated all tissue flaps using contrast-enhanced MRI (Magnetom Symphony TIM®, Siemens) with a 3D-VIBE sequence and a time resolution of 7s. Thus, the transplants were completely captured in all cases. As perfusion parameters, the positive enhancement integral (PEI) as well as the maximum intensity projection time (MIP-time) were collected. For comparison of both applications, all parameters were displayed in color-coded resolution and analyzed by three independent readers. Depending on the flap thickness, 1–3 regions of interest (ROI) were investigated. Each ROI measured 1 × 3 cm. Results: The subcutaneous ROI-1 showed a significantly lower rating regarding RBF in the ceMRI compared to CEUS (Mann-Whitney Rank-Sum test, p < 0.05). ROI-2 and -3 did not show any significant differences between the two applications. The frequency distribution showed good accordance in both modalities. Both imaging techniques detected 1 partial flap necrosis within the random area of cutaneous and subcutaneous layers, 1 hematoma as well as 1 insufficient perfusion over all tissue layers. After subsequent reoperation, graft loss could be prevented. Conclusion: At present, both technologies provide an optimal assessment of perfusion in cutaneous, subcutaneous and muscle tissue layers, whereby the detection of fatty tissue perfusion is currently more easily detected using CEUS compared to ceMRI. Show more

Keywords: Plastic surgery, tissue flaps, MRI, ceMRI, GD-DTPA, contrast enhanced ultrasound, CEUS, Sonovue, microcirculation

DOI: 10.3233/CH-2011-1405

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 105-117, 2011

Authors: Ruef, P. | Gehm, J. | Gehm, L. | Pöschl, J.

Article Type: Research Article

Abstract: Red blood cells (RBC) of neonates have a shorter survival time and they are more susceptible to mechanical alterations than RBC of adults. Irreversible alteration of the membrane of RBC of preterm neonates, term neonates and adults due to tether formation was studied by means of a micropipette technique. Shear stress and forces were applied with this technique in an axisymmetric configuration and were calculated with an approximation method. The applied shear stress and forces that induced tether formation were lowest for RBC of preterm neonates (1.5 Pa, 1.8 pN), in between for RBC of neonates (1.7 Pa, 2.1 pN) …and highest for RBC in adults (1.9 Pa, 2.6 pN). Decreased mechanical stability of the membrane of neonatal RBC may in part cause the shorter life span, the greater tendency to endocytosis and the higher amount of irregularly shaped cells of neonatal RBC compared to RBC in adults. Show more

Keywords: Erythrocyte, preterm, RBC, neonate, plastic deformation, tether

DOI: 10.3233/CH-2011-1390

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 119-128, 2011

Authors: Jung, F. | Mrowietz, C. | Hiebl, B. | Franke, R.P. | Pindur, G. | Sternitzky, R.

Article Type: Research Article

Abstract: 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. Show more

Keywords: Rheological parameters, microcirculation, capillary microscopy

DOI: 10.3233/CH-2011-1392

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 129-139, 2011

Authors: Clevert, D.A. | Sommer, W.H. | Helck, A. | Saam, T. | Reiser, M.

Article Type: Research Article

Abstract: Purpose: To evaluate neovascularisation within carotid atherosclerotic plaques with contrast enhanced ultrasound. Methods: We used contrast-enhanced ultrasound to examine 33 patients with carotid atherosclerotic plaques. Plaque size and echogenicity were analyzed and we correlated neovascularization within the plaques. Results: There were 41 atherosclerotic plaques, 27 plaques enhanced after the injection of a contrast agent. Among the group of enhancing plaques we found 8 soft- and 19 mixed plaques. The overall thickness ranging in enhanced plaques was from 1.8 to 4.6 mm. In all cases the contrast uptake in the plaques was later than in the carotid artery. Among the 14 …unenhanced atherosclerotic plaques, 4 plaques presented as hard plaques, three calcified plaques, two soft plaques and five presented as mixed plaques. The overall thickness ranging in unenhanced plaques was from 1.7 to 6 mm. Conclusion: Contrast-enhanced ultrasound allows the non invasive, dynamic evaluation of neovascularisation within carotid plaques. Show more

Keywords: Carotid artery, contrast enhanced ultrasound, plaque neovascularisation

DOI: 10.3233/CH-2011-1403

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 141-148, 2011

Authors: Helck, A. | Sommer, W.H. | Wessely, M. | Notohamiprodjo, M. | Reiser, M. | Clevert, D.A.

Article Type: Research Article

Abstract: Purpose: To evaluate the benefit of CEUS (contrast enhanced ultrasound) regarding depiction of ischaemic lesions and AVFs (arterio venous fistula) in renal transplants compared to standard ultrasound (US) (grey-scale and color Doppler). Materials and methods: In this study 22 patients suspected of having acute vascular complication after renal transplantation were investigated using standard ultrasound (grey-scale US and color Doppler US) and CEUS, respectively. Validity of the respective US-techniques regarding depiction of ischaemic lesions and AVF was compared. Dynamic CTA (computed tomography angiography) served as the standard of reference. Results: In 10 renal transplants arterial embolism associated with kidney infarctions were …observed. Very good correlation to dynamic CTA was yielded using CEUS, whereas grey scale US and color Doppler US was limited in the accurate depiction of renal infarctions. Additionally CEUS was superior in displaying arteriovenous fistulas compared to standard US. Conclusion: CEUS as a fast and bedside available imaging modality not associated with dose exposure or renal toxicity facilitates improved detection of ischaemic lesions and AVFs compared to standard US and thus should be considered for short term follow up of renal transplants. Show more

DOI: 10.3233/CH-2011-1398

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 149-160, 2011

Authors: Battig, Alexander | Hiebl, Bernhard | Feng, Yakai | Lendlein, Andreas | Behl, Marc

Article Type: Research Article

Abstract: Polydepsipeptides, alternating copolymers consisting of α-amino acids and α-hydroxy acids, are degradable polymers. Depsipeptide-based polymers of varied architectures can be synthesized via ring-opening polymerization of various morpholine-2,5-dione derivatives. Thermoplastic phase-segregated multiblock copolymers with poly(ε-caprolactone) (PCL) and poly(iso-butyl-morpholinedione) segments have been synthesized from the macrodiols and an aliphatic diisocyanate as a coupling agent. The respective multiblock copolymers showed shape-memory capabilities and good elastic properties, making them attractive candidates for potential application as biomaterials for controlled drug release systems, scaffolds to be applied in tissue engineering or biofunctional implants. Thus, these abilities cumulate to form multifunctional materials, combining degradability with shape-memory capability. …The advantages of depsipeptide-based multiblock copolymers compared to previously reported poly(ether)ester-derived biomaterials having shape-memory property may result from their different degradation products, as the resulting α-amino acids may act as a buffer for the hydroxy acids, thereby stabilizing pH values. In this context, we report on the biological evaluation of material samples in accordance with international standards (EN DIN ISO 10993-5 and 10993-12). Here, extracts of the substrates were exposed to a continuous fibroblast like cell line (L929) to study cytocompatibility of extractable substrates. Cell viability, morphology, LDH-release (as a parameter for the functional integrity of the cell membrane), activity of the mitochondrial dehydrogenases (as a parameter of the cell activity) and assembly of the actin- and vinculin cytoskeleton indicated no incompatibilities between the extracts and L929 cells. These results suggest that depsipeptide-based multiblock copolymers are promising candidates for soft, multifunctional implant materials. Show more

DOI: 10.3233/CH-2011-1391

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 161-172, 2011

Authors: Haacke, N. | Unger, J.K. | Haidenhein, C. | Russ, M. | Hiebl, B. | Niehues, S.M.

Article Type: Research Article

Abstract: Objective: In a porcine, aortic graft model we found 5 animals to develop and survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute occlusion but rather unspecific clinical symptoms. We investigated the pigs' vascular system to classify the anatomic capabilities to compensate for an acute abdominal aortic occlusion. Design of study: Retrospective analysis of CT scans and clinical data to specify unexpected results in a case series of infrarenal occlusion in a porcine model. Setting: Collaborative study of experimental and clinical departments. Subjects: Fifteen healthy female minipigs. Interventions: All pigs underwent an infrarenal aortic graft intervention. Anesthesia …and perioperative management of the animals were preformed along the standard operating procedures of the local Department of Experimental Medicine. All animals received perioperative antibiotics, ASS, and carprofen for postoperative analgesia. Arterial pressure, heart rate, body temperature, and diuresis were monitored during surgery and therapeutic interventions. Main outcome measures: Contrast media based computed tomography (CT) with total body scans were performed at 1, 4, 10, 12 weeks after surgery. Comparable scans of cardiovascular healthy subjects (humans and pigs) and patients with a Leriche's syndrome were analyzed. Results: Neither acute (within the first 12 h after surgery) nor stepwise total aortic occlusion show unmistakable clinical signs. In pigs, the epigastric artery (EGA) – which is in connection with suprarenal lumbal arteries, subclavian and external iliac artery – is highly developed associated to the high number of mammary glands of about 7 on one side. In humans, the ratio of aortic to EGA-diameter is 1 : 0.15. In minipigs we found a ratio of 1 : 0.43 which changed during aortic occlusion resulting in a ratio of 1 : 0.58. Pigs with a slowly developing occlusion demonstrated an enlargement of the ureteric artery of about 210% completing a sufficient collateral system. Conclusion: While in the human Leriche's syndrome months are needed to enlarge the EGAs for a partial collateral support of an infrarenal aortic occlusion the pig's EGA is a naturally sufficient collateral system capable to cover immediately for an acute infrarenal aortic occlusion. Further collateral enlargement even provides a permanent, sufficient hind limb perfusion in pigs. As the sufficient collateral system probably reduce pressure and shear rates in the infrarenal aortic segment after cross clamping, pigs might have a higher predisposition to produce early thrombosis related graft occlusions tan humans. Show more

Keywords: Porcine model, abdominal aortic occlusion, paresis, rectal prolapse, Leriche syndrome, aortic surgery

DOI: 10.3233/CH-2011-1401

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 173-185, 2011

Authors: Fellner, C. | Prantl, L. | Rennert, J. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: Postoperative monitoring of transplanted free flaps is an essential tool to reveal possible complications. The aim of this study was to compare the value of time-intensity-curve- (TIC-) analysis based on grey scale data of contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI). Postoperative imaging was performed in 11 patients following free flap transplantation and TIC analysis was obtained in identical regions of interest (ROI) of CEUS and DCE MRI data. Microcirculation was assessed in superficial (0–1 cm), middle (1–2 cm), and deep (2–3 cm) ROIs in one or two different positions within the flap resulting in a …total of 46 ROIs evaluated (in very thin flaps only superficial and middle ROIs were assessed). For both imaging methods, mean signal increase was found to be significantly higher in ROIs of normally perfused flaps (n = 40) compared to ROIs with compromised microcirculation (n = 6). Although TIC analysis allows quantification of microcirculation in different regions of the flap, in this preliminary study no distinct threshold could be defined to differentiate flaps with normal and compromised microcirculation. Show more

Keywords: CEUS, MRI, TIC analysis, microcirculation, DCE, free flaps, plastic surgery

DOI: 10.3233/CH-2011-1399

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 187-198, 2011

Authors: Clevert, D.-A. | Sommer, W.H. | Helck, A. | Reiser, M.

Article Type: Research Article

Abstract: Purpose: The aim of the study was to evaluate whether contrast enhanced ultrasound (CEUS) can improve the visualization of in-stent restenosis after carotid stenting of the internal carotid artery (ICA) in comparison to color-coded duplex sonography (CCDS) and power Doppler. Material and Methods: The study included the follow up of thirty patients after carotid artery stenting (CAS). Intrastenotic flow detection and lengths of in-stent restenosis were the main criteria. A high-end ultrasound machine (Siemens, ACUSON, Sequoia or S2000™) with a multi-frequency linear 9 MHz or 15 MHz transducer was used to carry out contrast-enhanced ultrasound with SonoVue®. In cases of …treatment of a high degree in-stent stenosis intra-arterial digital subtraction angiography (DSA) was used. Results: All patients were examined using all diagnostic ultrasound tools of the study. In five patients (17%) an in-stent restenosis of the internal carotid artery (ICA) was found. Two patients need a reintervention. The results show that the contrast enhanced ultrasound could improve the diagnostic assessment capabilities in comparison to CCDS and power Doppler for patients with in-stent restenosis after carotid stenting of the ICA. Conclusion: Contrast enhanced ultrasound is a reliable method for the evaluation of in-stent restenosis after carotid stenting of the ICA. CEUS provides a reduction in intrastenotic flow artefacts, resulting in better visualisation and detection of the complete length of the stenosis in comparison with CCDS and power Doppler. In order to elucidate hemodynamic changes, additional Doppler examinations are still necessary. Show more

Keywords: Carotid artery, contrast enhanced ultrasound, in-stent restenosis

DOI: 10.3233/CH-2011-1400

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 1-3, pp. 199-208, 2011