Clinical Hemorheology and Microcirculation - Volume 74, issue 1

Authors: Jokisch, F. | Buchner, A. | Schulz, G.B. | Grimm, T. | Weinhold, P. | Pfitzinger, P.L. | Chaloupka, M. | Stief, C.G. | Schlenker, B. | Clevert, D.-A.

Article Type: Research Article

Abstract: PURPOSE: The evaluation of the potential clinical benefit of four-dimensional ultrasound (4D-US) in the assessment of bladder cancer (BC). MATERIAL AND METHODS: 20 patients with indication for cystoscopy for suspicion of bladder cancer were prospectively included in this study. All patients underwent two-dimensional ultrasound (2D-US), contrast enhanced ultrasound (CEUS) and real-time four-dimensional ultrasound (4D-US). All acquisitions were compared to each other in regard to image quality. This assessment was done using a 6 point scale (1 = best). All patients underwent subsequently cystoscopy with resection of the tumor (TURB), due a histopathological analysis was possible. RESULTS: All examinations …were performed successfully and no patient had to be excluded from the study. Patients acceptance of 4D-US was consistently good. No adverse events occurred. Image quality of real time 4D-US (score: 1.27±0.46) was significantly superior (p  < 0.001) to both, conventional 2D-US (score: 2.33±0.62) and also to 2D-CEUS (score: 2.00±0.53). In terms of tumor detection no superiority was evident for 4D-US compared to 2D-US or in utilization of CEUS (sensitivity = 0.89; specificity = 1.00; positive predictive value = 1.00; negative predictive value = 0.50; AUC = 0.944; (95% CI: 07.43–0.998)). CONCLUSION: The assessment of bladder cancer using real time 4D-US is feasible and improves the image quality and therefore also the precise anatomical consistency of intravesical tumor masses. Show more

Keywords: Bladder cancer detection, real-time 4D ultrasound, four-dimensional ultrasound of the bladder, ultrasound of bladder cancer

DOI: 10.3233/CH-199231

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 1-12, 2020

Authors: Puhr-Westerheide, D. | Kostbade, T. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Motorsport karting has developed into a professional international competition. Kart racing poses a unique set of physiologic challenges for athletes who compete in this sport. Until today no major study has evaluated the physical and cardiac challenge in professional kart racing. OBJECTIVE: The aim for this study was to measure and analyze heart rate and cardiac rhythm by a mobile, smartphone based ECG (s-patch) on professional kart-race-drivers during actual karting races through annual seasons to test the hypotheses that high g-force and stress could trigger cardiac arrhythmia. MATERIAL AND METHODS: ECG-data from kart-drivers were acquired …during local races, the ADAC Kart-Masters (KZ2), the German Kart Championship (DSKC) and the European Championship Senior CIK-FIA-Serie and analyzed in this observational study. In total, free practice, qualifying practice and 32 races were assessed during the kart season 2019. Data were interpreted by two independent experienced physicians. RESULTS: The average heart rate (HR) during a selected German Kart Championship (DSKC) race in Genk (Belgium) was 169 beats min-1. The longest R-R interval was 0.72 sec. The average HR during a selected European Championship CIK-FIA-race in Lonato (Italy) was 160 beats min-1. The longest R-R interval was 0.74 sec. The average HR during a selected ADAC Kart-Masters (KZ2) races in Wackersdorf (Germany) was 147 beats min-1. The longest R-R interval was 0.86 sec. In total 32 races could be recorded successful. No couplets or bigeminy cycles were detected. In one other kart racer a supraventricular extrasystole and a ventricular extrasystole was detected. Interestingly, kart-drivers were found to have sinustachycardia throughout the races most likely triggered by emotional and physiological stress during speeding. CONCLUSION: Professional kart racing drivers had sinustachycardia with heart rates up to 193 beats min-1 during races. This is most likely attributed to a considerably high emotional and physiological stress affecting the cardiovascular system. Episodes of tachycardia positively correlated with mean speed. In the warm-up lap the heart rate was significantly lower in comparison to the race, suggesting that faster driving speed would induce greater cardiovascular stress to professional drivers during actual races. The experimental results showed that the proposed S-patch system provided a good ECG signal quality with accurate measurements even during the kart race and could detect the ECG features of the race in real time. The cardiac interpretation software performs well and is a useful tool to assist clinicians. Show more

Keywords: S-patch, ECG, motorsport, karting

DOI: 10.3233/CH-199232

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 13-19, 2020

Authors: Sievers, H. | Hiebl, B. | Hünigen, H. | Hirschberg, R.M.

Article Type: Research Article

Abstract: BACKGROUND: Blood supply is an important factor for the normal function of the equine hoof, but earlier studies present conflicting data on functional characteristics of its angioarchitecture. OBJECTIVE: Emphasis was laid on demonstration of the microvascularisation in the different hoof wall regions, aiming at assessment of specialised vascular structures, e.g. vascular sphincter mechanisms and arteriovenous anastomoses. METHODS: The angioarchitecture of the adult pododerma in the equine hoof wall was examined by scanning electron microscopy of micro-corrosion casts assisted by exemplary histological and immuno-histochemical characterisation of the pododermal vasculature. RESULTS: The microvasculature of the lamellae …and terminal papillae in all hoof wall regions was described in detail. Focal dilations and microvascular sphincters were a common feature. In contrast to former investigations, true arteriovenous anastomoses were detected at the base of the primary lamellae and the terminal papillae only, while thoroughfare channels proved a regular element within the microvasculature of the wall proper. Bicuspid venous valves were detected as regular feature. For the first time, the alpha-smooth muscle actin-reactivity of the microvascularisation in the hoof wall was systematically assessed, verifying its specialised vasomotor devices. CONCLUSIONS: The vasculature of the hoof wall displays specific angio-adaptations to high pressure and tensile load. Show more

Keywords: Blood vessels, microcirculation, wall segment, dermal lamellae, terminal papillae, sphincter vessels, pododermal angiogenesis

DOI: 10.3233/CH-199233

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 21-44, 2020

Authors: Gehmert, Sanga | Lehoczky, Gyözö | Loibl, Markus | Jung, Friedrich | Prantl, Lukas | Gehmert, Sebastian

Article Type: Research Article

Abstract: INTRODUCTION: Stromal-epithelial interactions are fundamental for normal organ development and there is a multitude of evidence that the different components of the microenvironment are also necessary for the maintenance and promotion of the “tumor organ”. Deregulated tumor associated extracellular matrix (tECM) is a hallmark of cancer, causing an alteration in the amount and composition of the different components (i.e. proteins, proteoglycans, glycoproteins and polysaccharids) of the ECM. As epithelial-stromal interactions are reciprocal, it is possible that tECM itself is able to initiate tumor development. We therefore established a mouse model to examine the influence of tECM of murine breast cancer …on developing breast tissue in mice. MATERIALS AND METHODS: Breast cancer was established in 5 BALB/c mice by subcutaneous injection of 1×106 4T1 cells in 100μl PBS into the left mammary fat pad. The mammary fat pad including the primary tumor was excised after two weeks, decellularised and labelled as tumor extracellular matrix (tECM). Tumor ECM of 4T1 tumors was implanted into the 4th inguinal mammary fat pad of BALB/c mice (n  = 5) aged 5 days. After 12 weeks the fourth mammary fat pad including the primary tumor was excised. Tissue was used for paraffin embedding and mouse breast cancer PCR array. Murine breast cancer tissue (BCT) and normal murine breast tissue (BT) served as control. RESULTS: Gene array analysis of 84 breast cancer-specific transcripts revealed that the mammary gland cells which were exposed to tumor ECM (tECM-BT) showed a similarly high overexpression for 22 genes as apparent for breast cancer tissue (BCT). The corresponding scatter plot showed a high agreement in the expression of the examined genes between the mammary gland cells which were exposed to tumor ECM and the breast cancer tissue. DISCUSSION: Our results clearly demonstrate that the tECM is able to shift the gene expression pattern of murine mammary epithelial cells towards that of carcinoma, indicating a role in breast cancer initiation. These data underlines that the acellular component of the tumor (ECM) can lead to a transformation of mammary gland tissue cells. These data show for the first time that the interaction of normal breast tissue cells with tumor ECM leads to an exchange of information and a consecutive overexpression of tumor-specific genes. Show more

Keywords: Breast cancer, extracellular matrix, microenvironment, epithelial-stromal interaction

DOI: 10.3233/CH-199234

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 45-52, 2020

Authors: Tung, Wing Tai | Zou, Jie | Sun, Xianlei | Wang, Weiwei | Gould, Oliver E.C. | Kratz, Karl | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Microfibers with a core-shell structure can be produced by co-axial electrospinning, allowing for the functionalization of the outer layer with bioactive molecules. In this study, a thermoplastic, degradable polyesteretherurethane (PEEU), consisting of poly(p-dioxanone) (PPDO) and poly(ɛ -caprolactone) (PCL) segments with different PPDO to PCL weight ratios, were processed into fiber meshes by co-axial electrospinning with gelatin. The prepared PEEU fibers have a diameter of 1.3±0.5 μm and an elastic modulus of around 5.1±1.0 MPa as measured by tensile testing in a dry state at 37°C, while the PEEU/Gelatin core-shell fibers with a gelatin content of 12±6 wt% and a diameter of …1.5±0.5 μm possess an elastic modulus of 15.0±1.1 MPa in a dry state at 37 °C but as low as 0.7±0.7 MPa when hydrated at 37 °C. Co-axial electrospinning allowed for the homogeneous distribution of the gelatin shell along the whole microfiber. Gelatin with conjugated Fluorescein (FITC) remained stable on the PEEU fibers after 7 days incubation in Phosphate-buffered saline (PBS) at 37 °C. The gelatin coating on PEEU fibers lead to enhanced human adipose tissue derived mesenchymal stem cell (hADSC) attachment and a proliferation rate 81.7±34.1 % higher in cell number in PEEU50/Gelatin fibers after 7 days of cell culture when compared to PEEU fibers without coating. In this work, we demonstrate that water-soluble gelatin can be incorporated as the outer shell of a polymer fiber via molecular entanglement, with a sustained presence and role in enhancing stem cell attachment and proliferation. Show more

Keywords: PEEU, gelatin, electrospun fibers, mesenchymal stem cells, biomaterials

DOI: 10.3233/CH-199235

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 53-66, 2020

Authors: Lehoczky, Gyözö | Wolf, Francine | Mumme, Marcus | Gehmert, Sebastian | Miot, Sylvie | Haug, Martin | Jakob, Marcel | Martin, Ivan | Barbero, Andrea

Article Type: Research Article

Abstract: OBJECTIVE: Implantation of autologous chondrocytes for cartilage repair requires harvesting of undamaged cartilage, implying an additional joint arthroscopy surgery and further damage to the articular surface. As alternative possible cell sources, in this study we assessed the proliferation and chondrogenic capacity of debrided Knee Chondrocytes (dKC) and Nasal Chondrocytes (NC) collected from the same patients. METHODS: Matched NC and dKC pairs from 13 patients enrolled in two clinical studies (NCT01605201 and NCT026739059) were expanded in monolayer and then chondro-differentiated in 3D collagenous scaffolds in medium with or without Transforming Growth Factor beta 1 (TGFβ 1). Cell proliferation and …amount of cartilage matrix production by these two cell types were assessed. RESULTS: dKC exhibited an inferior proliferation rate than NC, and a lower capacity to chondro-differentiate. Resulting dKC-grafts contained lower amounts of cartilage specific matrix components glycosaminoglycans and type II collagen. The cartilage forming capacity of dKC did not significantly correlate with specific clinical parameters and was only partially improved by medium supplemention with TGFβ 1. CONCLUSIONS: dKC exhibit a reproducibly poor capacity to engineer cartilage grafts. Our in vitro data suggest that NC would be a better suitable cell source for the generation of autologous cartilage grafts. Show more

Keywords: Nasal chondrocytes, cartilage repair, tissue engineering, chondrogenic differentiation, articular cartilage

DOI: 10.3233/CH-199236

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 67-78, 2020

Authors: Wernly, Bernhard | Pernow, John | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: In the microcirculation, the exchange of nutrients, water, gas, hormones, and waste takes place, and it is divided into the three main sections arterioles, capillaries, and venules. Disturbances in the microcirculation can be measured using surrogate parameters or be visualized either indirectly or directly. Arginase is a manganese metalloenzyme hydrolyzing L-arginine to urea and L-ornithine. It is located in different cell types, including vascular cells, but also in circulating cells such as red blood cells. A variety of pro-inflammatory factors, as well as interleukins, stimulate increased arginase expression. An increase in arginase activity consequently leads to a consumption of …L-arginine needed for nitric oxide (NO) production by endothelial NO synthase. A vast body of evidence convincingly showed that increased arginase activity is associated with endothelial dysfunction in larger vessels of the vascular tree. Of note, arginase also influences the microcirculation. Arginase inhibition leads to an increase in the bioavailability of NO and reduces superoxide levels, resulting in improved endothelial function. Arginase inhibition might, therefore, be a potent treatment strategy in cardiovascular medicine. Recently, red blood cells emerged as an influential player in the development from increased arginase activity to endothelial dysfunction. As red blood cells directly interact with the microcirculation in gas exchange, this could constitute a potential link between arginase activity, endothelial dysfunction and microcirculatory disturbances. The aim of this review is to summarize recent findings revealing the role of arginase in regulating vascular function with particular emphasis on the microcirculation. Show more

Keywords: Microcirculation, arginase, atherosclerosis, intensive care, intravital microscopy, nitric oxide

DOI: 10.3233/CH-199237

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 79-92, 2020

Authors: Lau, S. | Rangarajan, R. | Krüger-Genge, A. | Braune, S. | Küpper, J.-H. | Lendlein, A. | Jung, F.

Article Type: Research Article

Abstract: Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies. In our approach, HAEC from 16 donors of varying age (16–63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status. No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p  = 0.0374) and …the membrane integrity marginally impaired (p  = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors. According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly. Show more

Keywords: Cardiovascular implants, arterial endothelial cells, aging, senescence, donor variability

DOI: 10.3233/CH-199238

Citation: Clinical Hemorheology and Microcirculation, vol. 74, no. 1, pp. 93-107, 2020