Clinical Hemorheology and Microcirculation - Volume 67, issue 3-4

Authors: Jünger, M. | Krüger-Genge, A. | Jung, F.

Article Type: Editorial

DOI: 10.3233/CH-179200

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 209-209, 2017

Authors: Lamby, P. | Prantl, L. | Krüger-Genge, A. | Franke, R.P. | Jung, E.M. | Jung, F.

Article Type: Research Article

Abstract: Ultrasound contrast agents (USCA) allows the dynamic detection of blood flow of both the macro and microvasculature. An obvious prerequisite for USCAs is the unhindered passage of clinically relevant dose levels through the microcirculation especially of the lungue, where they have to pass capillaries with diameters of around 4 μm. While smaller microbubbles rapidly passed through the microcirculation along with the red blood cells, larger microbubbles, however, were observed to coalesce and interrupt the blood flow. Whether this might influence the tissue oxygen tension is unclear up to now. To examine this question a bolus of 2.4 ml SonoVue™ was …injected into the suprarenal aorta at a flow rate of 10 ml/s (a dosage usually applied in the clinic). The pO2 in the outer medulla of the kidney was continuously measured using a flexible pO2 microcatheter. In addition, the SonoVue™ injection and its passage through the renal vasculature were documented by the CEUS technology to assess whether the microbubbles passed the kidney. The study revealed that SonoVue™ induced no changes of the mean oxygen partial pressure in the outer medulla which confirms that these microbubbles on their way through the medullar capillaries did not hinder the co-flow of blood through the renal microvessels in a big animal model with a renal morphology and function comparable to human kidneys. These results demonstrate that the CEUS diagnostic itself did not influence the system to be examined which is a most important prerequisite for any diagnostic method. Show more

Keywords: CEUS, iodixanol, Iopromide, microcirculation, kidney

DOI: 10.3233/CH-179201

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 211-214, 2017

Authors: Strauss, Catharina | Brix, Eva | Anker, Alexandra | Prantl, Lukas | Brébant, Vanessa | Aung, Thiha

Article Type: Research Article

Abstract: BACKGROUND: Intra- and postoperative assessment of perfusion with near-infrared fluorescence imaging is commonly used among plastic surgeons to evaluate the quality of a microsurgical anastomosis in free flaps. OBJECTIVE: As microsurgical anastomosis can be monitored with near-infrared fluorescence imaging there is potential concerning revascularized fingers and hands with soft tissue depths not exceeding 7 mm above anastomosis. In a case of a severe crush injury of the hand more information about the perfusion was necessary as clinical assessment suspected loss of perfusion. METHODS: A 49-year old male suffered from a severe crush injury of his left hand …with dissection of the ulnar superficial palmar arterial arch and a lesion of median nerve. After revascularization and reconstruction of the nerve, the patient developed postoperatively a loss of perfusion of thumb and index finger. An evaluation of the perfusion status was obtained by fluorescence imaging after intravenous application of ICG. RESULTS: After intravenous application of ICG the near-infrared imaging showed a delayed but sufficient perfusion of the hand so that a salvage surgery was not indicated. CONCLUSIONS: In scenarios of critical perfusion in revascularized fingers and hands, the perfusion control via application of ICG and near-infrared fluorescence imaging can be a helpful tool. Show more

Keywords: Indocyanine green, perfusion control, revascularized hands

DOI: 10.3233/CH-179202

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 215-219, 2017

Authors: Saemann, Lars | Lachner, Karin | Wenzel, Folker

Article Type: Research Article

Abstract: INTRODUCTION: In the field of cardiovascular diseases an ergometer test is a common diagnostical method in which a change in microcirculation can be reached. In this paper cardiac frequency and cutaneous microcirculation during and after exercising will be compared with each other. MATERIALS AND METHODS: The cutaneous microcirculation of  6 healthy volunteers (2 females, 4 males) is measured. As an instrument the PeriFlux 5000 combined with a Laser-Doppler-Flow(LDF)-Probe (Perimed Instruments) is used. The cardiac frequency (CF) is measured by the POLAR T31 sensor and as an ergometer the ERGO-FIT ® 457 is used. RESULTS: The mean …initial LDF (97,7±57,3 PU) decreases at the beginning (64,5±21,7 PU), increases during theexercise, reaches its maximum (247,8±82,1 PU) after the end of the exercise and drops to lower values (256,4±69,5 PU)after a few minutes. Contrasting to the LDF the mean initial CF (86±22/min) increases at the beginning (97±9/min),furthermore during the whole exercise (103±9/min) and then falls after having finished the exercise (96±3/min).Furthermore, during regeneration, one can see the CF decreasing towards its initial value, while LDF reaches its maximum. CONCLUSION: In further studies, realized with volunteers with well-known levels of physical condition, a directconnection between cutaneous microcirculation and physical condition might be found. Show more

Keywords: Exercise, cardiac frequency, cutaneous microcirculation, physical condition, ergometer test, regeneration

DOI: 10.3233/CH-179203

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 221-227, 2017

Authors: Lutze, Stine | Daeschlein, G. | Konschake, W. | Jünger, Michael

Article Type: Research Article

Abstract: A complex pathomechanism accounts systemic sclerosis as a form of collagenosis. A triad of vasculopathy, autoinflammation, and dysbalance of the fibroblast function can be seen as cause, as well as symptomatic appearance. Comparative with other collagenoses, e.g. Lupus erythematosus, vasculopathy, instead of autoinflammation, appears to be clinically important in systemic scleroderma. The fact that autoinflammation does not represent the major role in the maintenance of the disease is also evident by the lack of therapeutic effects of classical systemic immunosuppressants. Therapeutic approaches with regard to vasculopathy show better effects. In consideration of therapeutic options, such principles are therefore most important. …Apheretic methods filter out plasma proteins in the sense of plasmapheresis. Fibrinogen as a plasma viscosity factor is predominantly targeted and filtered out. In addition other accompanying plasma proteins are also reduced. This occurs on the one hand by dilution effects and on the other by unspecific binding. By this mechanism, acute phase proteins such as the C-reactive protein and various cytokines, especially interleukin-6 are reduced by this method. Looking more closely at these random adjunctive plasma proteins, a possible central role of interleukin-6 in the development and maintenance cascade of systemic scleroderma becomes clear. Show more

Keywords: Systemic scleroderma, SSc, rheopathy, plasmapheresis, acute ulcers, interleukin-6

DOI: 10.3233/CH-179204

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 229-240, 2017

Authors: Thorburn, Taylor | Aali, Maral | Kostek, Lisanne | LeTourneau-Paci, Chloe | Colp, Patricia | Zhou, Juan | Holbein, Bruce | Hoskin, David | Lehmann, Christian

Article Type: Research Article

Abstract: BACKGROUND: Iron catalyzes the generation of reactive oxygen species (ROS) as part of the innate antimicrobial defense. During sepsis, the dysregulated systemic inflammatory response to infection, iron homeostasis becomes disrupted, generating an excess of ROS causing damage to tissues. This can be potentially suppressed using iron chelators that selectively bind iron to prevent its participation in ROS-related inflammatory reactions. OBJECTIVE: We hypothesize that administration of DIBI, a novel iron-chelator, attenuates the dysregulated systemic immune response and reduces tissue damage in experimental endotoxemia. METHODS: Five groups of animals (n  = 5–10) were included in this study: control, untreated …endotoxemia, and endotoxemia animals treated with either DIBI-A, MAHMP, or DIBI-B. Intravital microscopy was performed on the intestine of anesthesized mice to observe leukocyte endothelial interactions and evaluate the intestinal microcirculation. RESULTS: Treatment of endotoxemic mice with DIBI-B reduced the number of adhering leukocytes in submucosal collecting (V1) venules by 68%. DIBI-B, MAHMP, and DIBI-A were able to restore functional capillary density (FCD) in the intestinal muscle layer by 74%, 44%, and 11%, respectively. CONCLUSIONS: DIBI-B reduces leukocyte recruitment and improves FCD in experimental endotoxemia, outperforming other chelators tested. These findings suggest a potential role for DIBI-B as a candidate drug for sepsis treatment. Show more

Keywords: Intravital microscopy, leukocyte adhesion, functional capillary density (FCD), microcirculation, inflammation, iron chelation, endotoxemia

DOI: 10.3233/CH-179205

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 241-250, 2017

Authors: Blocki, Anna | Löper, Farina | Chirico, Nino | Neffe, Axel T. | Jung, Friedrich | Stamm, Christof | Lendlein, Andreas

Article Type: Research Article

Abstract: Cell-based therapies often face the challenge of low cell retention and viability upon transplantation. Hence, biomaterials, which can immobilize transplanted cells, while at the same time support cell viability, are essential for successful clinical application. Noteworthy, biomaterials in the micrometer range such as microcapsules or microspheres have the advantage of a minimally invasive introduction into tissue. Hence, we established an approach to generate gelatin-based cell carriers in the form of microspherical hydrogels. Fibroblasts were microencapsulated in glycidylmethacrylate (GMA)-functionalized gelatin by photopolymerization. While the degree of GMA-functionalization was kept constant, the hydrogel cross-linking density was adjusted by varying the time …of irradiation or the average gelatin-chain length. Stable microspheres were synthesized from 10 wt% GMA-gelatin solutions for all irradiation periods tested (0.5 –2 min). Evaluation of cell viability revealed that microgels with the same weight content of biopolymer but with decreased cross-linking densities and thus decreased storage and E modulus, resulted in best cell support. Noteworthy, encapsulated cells partially migrated out of the microspheres and attached to the spherical surface. 10 wt% GMA-gelatin-based hydrogels with E moduli comparable to the native cellular niche proved to be a promising biomaterial suitable for the production of cell-laden microspheres and shall be evaluated further for biomedical application. Show more

Keywords: Gelatin, hydrogel, cell encapsulation, microspheres, microgels, microbeads

DOI: 10.3233/CH-179206

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 251-259, 2017

Authors: Beye, Aida | Pindur, Gerhard

Article Type: Research Article

Abstract: Cerebrovascular diseases are considered in a different way concerning their etiology with regard to arterial and venous occlusion. The role of thrombophilia in this context remains undetermined. For this reason, a case-control study was conducted including a total of 202 patients (154 females, 48 males) aged from 18 to 76 years (mean: 39.8 years) suffering either from cerebral sinus venous thrombosis (n  = 101) or from arterial ischemic stroke (n  = 101). Study groups were evaluated on the basis of age- and gender-matched pairs. Gene mutations of factor V-1691 (factor V Leiden) and prothrombin-20210 being considered as the most common thrombophilia markers …were analyzed in this study. Factor V Leiden-mutations were found in 16.8% of patients with cerebral sinus venous thrombosis (CVT) and in 17.8% of patients with arterial ischemic stroke (AIS), which was significantly more frequent than in controls at a rate of 4.95% (ORs: 3.89 and 4.16). Prothrombin-mutations were significantly more frequent in CVT at a rate of 14.9% versus 2.97% in controls (OR: 5.70). This does not apply for AIS showing a rate of 4.95% prothrombin-mutations. Rates of factor V Leiden-mutations are not different in CVT compared with AIS. In contrast, however, prothrombin-mutations were significantly more frequent in CVT than in AIS with a rate of 14.9% versus 4.95% (OR 3.35). Furthermore, 3 cases with combined heterozygosity of factor V Leiden- and prothrombin-mutation have been identified in CVT, but not in AIS or controls. All of the above mentioned mutations were exclusively heterozygous. We conclude from these data that thrombophilia in terms of factor V Leiden genotype is a risk factor for both CVT and AIS in equal measure. In contrast, prothrombin-20210-mutations were different playing a significant role in the pathogenesis of cerebral sinus vein thrombosis, but not in arterial ischemic stroke. Also, the combined occurrence of heterozygous prothrombin- and factor V Leiden-mutation clearly favors the emergence of cerebral sinus venous thrombosis. Therefore, in terms of thrombophilia such as investigated in this study, pathogenesis of arterial and venous occlusions in cerebrovascular disease has to be regarded as different. Show more

Keywords: Cerebral venous thrombosis, arterial ischemic stroke, thrombophilia

DOI: 10.3233/CH-179207

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 261-266, 2017

Authors: Li, Zhengdong | Xu, Xun | Wang, Weiwei | Kratz, Karl | Sun, Xianlei | Zou, Jie | Deng, Zijun | Jung, Friedrich | Gossen, Manfred | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Controlling mesenchymal stem cells (MSCs) behavior is necessary to fully exploit their therapeutic potential. Various approaches are employed to effectively influence the migration capacity of MSCs. Here, topographic microstructures with different microscale roughness were created on polystyrene (PS) culture vessel surfaces as a feasible physical preconditioning strategy to modulate MSC migration. By analyzing trajectories of cells migrating after reseeding, we demonstrated that the mobilization velocity of human adipose derived mesenchymal stem cells (hADSCs) could be promoted by and persisted after brief preconditioning with the appropriate microtopography. Moreover, the elevated activation levels of focal adhesion kinase (FAK) and mitogen-activated protein kinase …(MAPK) in hADSCs were also observed during and after the preconditioning process. These findings underline the potential enhancement of in vivo therapeutic efficacy in regenerative medicine via transplantation of topographic microstructure preconditioned stem cells. Show more

Keywords: Mesenchymal stem cells, precondition, microstructure, migration, FAK-MAPK

DOI: 10.3233/CH-179208

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 267-278, 2017

Authors: Wang, Weiwei | Li, Wenzhong | Wang, Jinlei | Hu, Qinglian | Balk, Maria | Bieback, Karen | Stamm, Christof | Jung, Friedrich | Tang, Guping | Lendlein, Andreas | Ma, Nan

Article Type: Research Article

Abstract: Mesenchymal stem cells (MSCs) are targeted as vehicles for cell mediated gene therapy. Here we report on a macromolecular carrier, which was designed aiming at successful targeted gene delivery into MSCs through the mediation of folate receptor and reduced cytotoxicity compared to established cationic polymer vector – polyethylenimine with a weight average molecular weight (Mw ) of 25,000 Dalton (PEI25K). The carrier PHPA-PEI1800-FA was synthesized in a two-step procedure. PHPA-PEI1800 was prepared by grafting polyethylenimine with a Mw of 1800 Dalton (PEI1800) onto the α,β-poly(N-3-hydroxypropyl)-D,L-aspartamide (PHPA) backbone. PHPA-PEI1800-FA was obtained by chemically conjugating folic acid onto PHPA-PEI1800. The grafting …degree of PEI1800 was 3.9±0.2% in relation to the CH groups of PHPA and the molar ratio of folic acid conjugated to PEI1800 (χ FA ) was 1.8±0.1 as calculated by NMR spectroscopy. The copolymers were biodegradable and exhibited lower cytotoxicity than PEI25K. Compared to PHPA-PEI1800, PHPA-PEI1800-FA led to a significantly higher transfection efficiency in human MSCs, which could be attributed to the mediation of folate receptor during the transfection process as confirmed by folic acid competition assay. Both marker gene (GFP) and therapeutic gene (VEGF) were delivered into human MSCs from multi-donors using PHPA-PEI1800-FA. The percentage of GFP+ MSCs showed an average value of 2.85±1.60% but a large variation for different samples. The VEGF expression level of the PHPA-PEI1800-FA transfected cells was significantly higher than that of either untransfected or naked DNA transfected cells. Conclusively, PHPA-PEI1800-FA is a suitable vector to deliver genes into human MSCs through the interaction with folate receptor. Show more

Keywords: Non-viral gene delivery, mesenchymal stem cells, folate receptor, poly(N-3-hydroxypropyl)aspartamide, polyethylenimine

DOI: 10.3233/CH-179209

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 279-295, 2017

Authors: Zou, Jie | Wang, Weiwei | Neffe, Axel T. | Xu, Xun | Li, Zhengdong | Deng, Zijun | Sun, Xianlei | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: Polymeric matrices mimicking multiple functions of the ECM are expected to enable a material induced regeneration of tissues. Here, we investigated the adipogenic differentiation of human adipose derived mesenchymal stem cells (hADSCs) in a 3D architectured gelatin based hydrogel (ArcGel) prepared from gelatin and L-lysine diisocyanate ethyl ester (LDI) in an one-step process, in which the formation of an open porous morphology and the chemical network formation were integrated. The ArcGel was designed to support adipose tissue regeneration with its 3D porous structure, high cell biocompatibility, and mechanical properties compatible with human subcutaneous adipose tissue. The ArcGel could support initial …cell adhesion and survival of hADSCs. Under static culture condition, the cells could migrate into the inner part of the scaffold with a depth of 840±120 μm after 4 days, and distributed in the whole scaffold (2 mm in thickness) within 14 days. The cells proliferated in the scaffold and the fold increase of cell number after 7 days of culture was 2.55±0.08. The apoptotic rate of hADSCs in the scaffold was similar to that of cells maintained on tissue culture plates. When cultured in adipogenic induction medium, the hADSCs in the scaffold differentiated into adipocytes with a high efficiency (93±1%). Conclusively, this gelatin based 3D scaffold presented high cell compatibility for hADSC cultivation and differentiation, which could serve as a potential implant material in clinical applications for adipose tissue reparation and regeneration. Show more

Keywords: Mesenchymal stem cells, gelatin based scaffold, adipose tissue regeneration, adipogenic differentiation

DOI: 10.3233/CH-179210

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 297-307, 2017

Authors: Krüger-Genge, A. | Hiebl, B. | Franke, R.P. | Lendlein, A. | Jung, F.

Article Type: Research Article

Abstract: In drug eluting stents the cytostatic drugs Sirolimus or Tacrolimus are used to inhibit blood vessel restenosis by limiting the proliferation of smooth muscle cells. However, the cytostatic activity of both drugs was shown to be not cell specific and could also affect the stent endothelialisation, respectively. Currently, only limited in vitro data are available about the impact of Sirolimus and Tacrolimus on endothelial cell proliferation over a broad concentration range. To answer this question the following study was performed. Commercially obtained HUVEC were expanded with DMEM cell culture medium (GIBCO, Germany) supplemented with 5 vol% fetal calf …serum on non-coated regular polystyrene-based 24-multiwell plates. For drug testings 2×104 cells/cm2 were seeded and grown for 24 h until 30–40% of the multiwell surfaces were covered and then exposed to Sirolimus (1.0×10–11 – 1.0×10–5  mol/l) or Tacrolimus (2.0×10–8 – 6.2×10–5  mol/l), both dissolved in DMSO. 12, 24 and 48 h after adding the drugs cell numbers per area were quantified by counting the cells in six wells with four fields of view per well, representing 0.6 mm2 , using a confocal laser microscope. After 48 h of cell growth in the drug-free cell culture medium, the HUVEC number increased from 2.0×104 to 3.55×104 cells/cm2 (mean cell doubling time: 53.6 h, n = 6). At lower concentrations (≤2.0×10–6  mol/l) Tacrolimus reduced the number of adherent HUVEC significantly less than Sirolimus (p  < 0.05). However, at higher concentrations (≥2.07×10–5  mol/l) the effect of Tacrolimus on the number of adherent endothelial cells was significantly greater than that of Sirolimus (p  < 0.05). At the highest concentration applied (6.22×10–5  mol/l), Tacrolimus induced detachment of all HUVECs within 12 h after drug application. The number of adherent HUVEC decreased only slightly (about 9%) after Sirolimus application at the highest concentration (1.09×10–5  mol/l). These data show that in a non-flow model the cytostatic drug Tacrolimus reduced the number of adherent endothelial cells less than Sirolimus, as long as the drug concentration did not surpass 10–6  mol/l. At the limits of solubility, Sirolimus (1×10–5  mol/l) reduced the number of adherent endothelial cells less than Tacrolimus (6×10–5  mol/l), which induced detachment of endothelial cells. Show more

Keywords: Endothelial cells, Sirolimus, Tacrolimus, DMSO

DOI: 10.3233/CH-179211

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 309-318, 2017

Authors: Broer, P. Niclas | Aung, Thiha | Heidekrueger, Paul I. | Prantl, L. | Narayan, Deepak

Article Type: Research Article

Abstract: OBJECTIVE: The interleukin-1 receptor antagonist (IL-1RA) contributes to tumor survival and progression in multiple cancer entities. IL-1RA polymorphisms influence IL-1RA expression patterns and function. A known polymorphism was correlated with clinical outcomes in melanoma patients with particularly aggressive disease. METHODS: DNA of 343 controls and 97 melanoma patients with poor prognostic indicators (time from diagnosis to death, nodal status, metastasis) was analyzed for a variable number of tandem repeat polymorphisms (VNTR) of the IL-1RA gene. Five alleles containing two (allele 2), three (allele 4), four (allele 1), five (allele 3) or six (allele 5) 86-bp repeats were targeted …via PCR amplification. RESULTS: Genotype 1/2 is less common in the melanoma patient group vs. the control (28.8% vs. 39.6%; p  = 0.06). Significant was the stage of the melanoma in order to predict the survivability (p  = 0.008). The 1/1 and 1/2 genotype appeared to have lower hazards ratios than the 2/2 genotype (p  > 0.05). CONCLUSIONS: Compared to the general population, the distribution of alleles coding for IL-1RA is different in melanoma patients. This alteration and the potential impact on tumor protein function and systemic inflammatory response may warrant further investigation. Show more

Keywords: Melanoma, interleukin-1 receptor antagonist, IL-1RA, polymorphism, inflammation

DOI: 10.3233/CH-179212

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 319-326, 2017

Authors: Lutter, Anne-Helen | Scholka, Jenny | Richter, Heiko | Anderer, Ursula

Article Type: Research Article

Abstract: BACKGROUND: Tetrazolium-based assays are optimized to assess proliferation/toxicity of monolayer or suspension cells in microtiter plates. With regard to tissue engineering and regenerative medicine the need for in vivo like 3D microtissues has an increasing relevance. Applying tetrazolium-based assays to 3D culture systems is technically more challenging. The composed microenvironment may influence the assay standards, e.g. equal distribution of tetrazolium. OBJECTIVE: Evaluation of membrane-impermeable tetrazolium salt-based assays with regard to spheroid culture (3D) of human chondrocytes. METHODS: Chondrocytes were isolated from human articular cartilage. XTT, WST-1, and WST-8 were applied to monolayer cells (2D, varying …cell numbers) and spheroids (3D, different sizes) in 96well plates. Formazan formation was measured spectrophotometrically after different incubation periods. Evaluation was done using phase contrast microsopy (toxicity), analyzing the correlation of cell number and absorbance signals (Gompertz function), and document signal over background ratio. RESULTS: In monolayer culture the assays showed a correlation between seeded cell numbers and absorption data. Spheroid sizes are directly related to the starting cell number. A correlation between size and absorbance was only detectable starting from 10,000 cells/aggregate. Phase contrast microscopy of monolayer cells revealed strong toxicity effects of the WST-1 (4 h) and XTT (8 h) assay and no signs of toxicity using WST-8. CONCLUSION: The WST-8 assay is non-toxic and revealed the highest sensitivity in comparison to the XTT or WST-1 assay. There is evidence, that only cells of the outer rim of spheroids are able to convert membrane-impermeable tetrazolium salts to formazans. Show more

Keywords: XTT, WST-1, WST-8, human chondrocytes, spheroid, 3D culture, 2D culture

DOI: 10.3233/CH-179213

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 327-342, 2017

Authors: Anadol, Remzi | Gori, Tommaso

Article Type: Research Article

Abstract: Coronary scaffolds have been recently developed to address the long-term limitations of metallic drug eluting stents. Concerns have however been expressed on the safety of these devices, with evidence of both early and late scaffold thrombosis. While early thrombosis has been associated with incomplete scaffold expansion, leading to flow disturbances, blood recirculation, and platelet activation, the pathophysiology of late events remains less understood. Recent cases series have shown that malapposition and scaffold dismantling might play a role in this phenomenon, an observation that further confirms the importance of an accurate implantation. Further, the role of dual antiplatelet therapy, and whether …prolonging it may reduce event rates, remains to be elucidated. As well, the role of inflammatory phenomena has been proposed but never demonstrated. This brief review summarizes the current evidence on these phenomena. Show more

Keywords: Bioresorbable scaffolds, stent thrombosis

DOI: 10.3233/CH-179214

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 343-346, 2017

Authors: Mrowietz, C. | Franke, R.P. | Pindur, G. | Wolf, U. | Jung, F.

Article Type: Research Article

Abstract: The Laser Doppler technique (Laser-Doppler-Fluxmetry, LDF), a noninvasive method to estimate skin blood flow (LDF), is frequently used in research and clinical routine [1 ]. Here, the measurements were carried out with a new Laser Doppler system, the DOP-system, which allows to measure frequency spectra in four different frequency windows according to the velocities in venules (low velocity), capillaries (low to medium velocities), and in arteries (with high and very high velocities). However, the diagnostic reliability or the effectiveness of the LDF has not yet been evaluated sufficiently, which is indispensable, where medical diagnostics and therapy controls are concerned. For …a valid interpretation of LDF values of individual patients, the knowledge of the reference range and the variability of the measured parameters is required. In four successive studies the reference range (62 apparently healthy subjects), the circadian variability (8 subjects), the variability from day-to-day (6 subjects) and over one year with monthly measurements (6 subjects) were evaluated. With the knowledge of the reference range, microcirculatory disorders can now be diagnosed using the DOP method. Following a standard measurement procedure there was no dependence of the measured data on the day or season of measurement. Show more

Keywords: Laser Doppler Flux, reference range, variability, skin perfusion

DOI: 10.3233/CH-179215

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 347-353, 2017

Authors: Ranieri, M. | Wohlgemuth, W. | Müller-Wille, R. | Prantl, L. | Kehrer, A. | Geis, S. | Klein, S. | Lamby, P. | Schiltz, D. | Uller, W. | Aung, T. | Dolderer, J.H.

Article Type: Research Article

Abstract: This article presents our experience in managing peripheral vascular malformations of upper and lower extremities over a 4-year period in a series of 46 patients of the Department of Plastic Surgery treated in the Interdisciplinary Center of Vascular Anomalies (ICVA) at the University of Regensburg. The patients presented vascular malformations of upper and lower extremity and were selected from our prospective vascular anomalies file archive from 2012 to 2016. During this period in the ICVA at University of Regensburg were performed more than 1400 radiological interventional treatments in patients with vascular malformations. The purpose of this retrospective study was …to review combined embolotherapy, sclerotherapy (embolo/sclerotherapy), and surgical procedures (surgical excision and soft tissue reconstruction) to manage vascular malformations. Treatments were principally induced to reduce pain, daily physical limitations, social discomfort and recover tegument continuity after ulceration. The 46 patients were first examined with noninvasive radiological procedures. After diagnosis was posed, embolo/sclerotherapy, surgical procedures and clinically as well as radiological follow-ups were coordinated and established by the multidisciplinary team. All vascular malformations were categorized according to the classification approved at the April 2014 General Assembly of International Society for the Study of Vascular Anomalies (ISSVA) in Melbourne, Australia. Arteriovenous malformations (AVMs) were further classified following the Cho-Do and Schobinger classification. Embolo/sclerotherapy shows to be the most appropriate procedure in vascular malformations treatment. Nevertheless was found that in case of complications or lack of improvement as well as to improve functional or aesthetical results, a following partial or complete surgical excision and immediate soft tissue reconstruction seems to be the gold-standard treatment. In addition, the precise clinical and radiological diagnosis as well as an intensive postoperative patient care have a significant positive influence on the clinical outcome and patient satisfaction while decreasing morbidity and recurrence during early and late follow-up. Vascular malformations require a multidisciplinary approach and individual treatment after complex excision and indispensable reconstruction. Show more

Keywords: Vascular malformations, vascular malformations surgical therapy, vascular malformations soft tissue reconstruction, interdisciplinary treatment vascular malformations

DOI: 10.3233/CH-179216

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 355-372, 2017

Authors: Haimerl, M. | Brünn, K | Poelsterl, S. | Beyer, L.P. | Wiesinger, I. | Stroszczynski, C. | Jung, E.-M. | Wiggermann, P.

Article Type: Research Article

Abstract: PURPOSE: To compare the diagnostic performance of real-time maximum liver capacity (LiMAx) with dynamic contrast-enhanced ultrasound (CEUS)-based liver microcirculation. MATERIALS AND METHODS: 23 patients underwent liver function capacity (LiMAx) test and consecutive or previous CEUS examinations. A bolus injection of 1.4 ml sulfur hexafluoride microbubbles was administered for CEUS measurements (1–6 MHz) and quantitative perfusion analysis (TIC) was performed with an integrated perfusion software using stored cine-loops. Two perfusion-parameters, time to peak (TtoP) and area under the curve (Area), were evaluated in liver parenchyma and portal vein using TIC analysis. To compare quantification parameters, patients were classified in patients representing …a healthy population (LiMAx value >315 μg/kg/h) and those representing patients with liver disease (LiMAx value <315 μg/kg/h). RESULTS: Comparing perfusion parameters derived from portal vein measurements, TtoP and Area were higher in patients with normal liver function TtoP: 25.0±8.4 s, Area: 1483±920 a.u. compared to patients with impaired liver function TtoP: 22.4±14.0 s; Area 1351±1212 a.u. This difference however was not statistically significant (p  = 0.52, p  = 0.48). In parameters derived from measurements in liver parenchyma TtoP was higher (38.5±11.3 s) and Area was lower (999±632 a.u.) in patients with normal liver function compared to patients with impaired liver function (TtoP; 30.6±11.0 s, p  = 0.156; Area: 1202±719 a.u.) (p  = 0.16, p  = 0.56). In a simple linear regression model, none of the perfusion parameters measured in portal vein (TtoP portal, Area portal) and liver parenchyma (TtoP liver, Area liver) correlated significantly with respective LiMAx values (p  = 0.194–0.950). CONCLUSION: Within the framework of this study, CEUS-based perfusion parameters were not able to assess severity of liver disease, assessed with LiMAx- test. Show more

Keywords: Liver capacity, LiMAx, CEUS, microcirculation, liver function

DOI: 10.3233/CH-179217

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 373-382, 2017

Authors: Pregler, B. | Beyer, L.P. | Wiesinger, I. | Haimerl, M. | Stroszczynski, C. | Jung, E.M. | Wiggermann, P.

Article Type: Research Article

Abstract: PURPOSE: To determine the influence of pre-interventionally existing portal vein thrombosis on the ablation success of percutaneous tumor ablation of HCC. MATERIALS AND METHODS: 15 patients with HCC and pre-existing portal vein thrombosis underwent thermal tumor ablation. We retrospectively analyzed the pre- and post-interventionally performed CT and MRI scans in terms of technical success as well as the complication rate. The portal vein thrombosis was classified into segmental, lobar and central thrombus. RESULTS: In 13/15 cases (87%) complete ablation with no evidence of residual tumor tissue was seen 6 weeks after the procedure in contrast-enhanced MRI …scans and contrast-enhanced ultrasound (CEUS). No major and 2 minor complications were observed after the ablation procedure. CONCLUSION: Reduced perfusion due to pre-interventionally existing portal vein thrombosis has no significant impact on the ablation success or the complication rate. Show more

Keywords: HCC, portal vein thrombosis, ablation, RFA, MWA

DOI: 10.3233/CH-179218

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 383-388, 2017

Authors: Zengel, Pamela | Reichel, Christoph Andreas | Vincek, Teresa | Clevert, Dirk André

Article Type: Research Article

Abstract: PURPOSE: Chronic recurrent parotitis (CRP) is a non-obstructive disease with episodes characterized by painful swelling of the parotid gland. It presents in both a juvenile and an adult form, with no clear information on its actual origin. Diagnosis is based on patient medical history and ultrasound examination but is frequently not correctly identified. Acoustic Radiation Force Impulse Imaging (ARFI) is a novel ultrasound elastography technology that has recently been implemented in the diagnostic work-up of patients with malignancies. This study aimed to answer whether ARFI can reasonably be employed in the initial examination and follow-up during therapy in patients with …CRP. MATERIAL AND METHODS: Mechanical tissue properties of the salivary glands were analyzed by ARFI in 37 parotid glands of patients with CRP. RESULTS: Having integrated ARFI into our diagnostic protocol for CRP, affected parotid glands were found to exhibit lower tissue elasticity compared to both healthy contralateral glands in the same individuals as well as those of healthy individuals. Most importantly, this method enabled us to quantitatively assess the patient benefit of therapy regarding the recovery of the glands’ diseased parenchyma. CONCLUSIONS: ARFI provides a quick, easy, and reliable diagnostic tool for the assessment of disease severity and progression in patients with CRP that can be seamlessly implemented into preexisting ultrasound protocols. Show more

Keywords: Chronic recurrent parotitis, ultrasound, elastography, ARFI imaging, tissue elasticity

DOI: 10.3233/CH-179219

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 389-397, 2017

Authors: Beyer, L.P. | Pregler, B. | Verloh, N. | Brünn, K. | Haimerl, M. | Stroszczynski, C. | Jung, E.M. | Wiggermann, P.

Article Type: Research Article

Abstract: OBJECTIVES: Irreversible electroporation (IRE) is a novel focal ablation technique applicable for treatment of prostate cancer (PCa). We aim to evaluate imaging findings of T1-weighted contrast-enhanced MRI after percutaneous IRE of low-risk PCa. METHODS: A total of 13 male patients underwent IRE of focal low-risk PCa and were included in this analysis. Prostate IRE was conducted using 2–4 electrodes being placed under CT-fluoroscopy guidance. Dynamic contrast-enhanced 3D isotropic fat-saturated T1-weighted MRI (DCE-MRI) was performed 24–72 hours before and 24–72 hours after ablation. RESULTS: Ablated prostate was either homogeneously (8/13 [62%]) or heterogeneously (5/13 [38%]) hypo attenuating. …Peripheral contrast enhancement manifesting as a hyper attenuating margin was observed during the arterial (60 sec) (3/13 [23%]) and venous (240 sec) (10/13 [77%]) phase. The ablation defect showed a sharp (8/13 [62%]) or blurry (5/13 [38%]) margin. CONCLUSIONS: The results show a venous peripheral rim enhancement in most of the cases, indicating reactive hyperaemia. The heterogeneous appearance of the defect zone in some cases may be secondary to sustained vascularization. Show more

Keywords: MRI, irreversible electroporation (IRE), prostate cancer, imaging findings

DOI: 10.3233/CH-179220

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 399-405, 2017

Authors: Mueller-Peltzer, K. | Rübenthaler, J. | Fischereder, M. | Habicht, A. | Reiser, M. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Vascular complications in renal transplant patients are a well-known issue in post transplant patient care. If malfunctioning of the renal transplant is suspected to be caused by vascular complications an early diagnosis and therapy is required to maintain the renal transplant. Computed tomography (CT), digital substraction angiography (DSA) and radioisotope renography are the gold standard imaging modalities to diagnose vascular complications. OBJECTIVE: To analyse the sensitivity and specificity of contrast-enhanced ultrasound (CEUS) in comparison to the standard imaging modalities CT, DSA and radioisotope renography in the diagnosis of vascular complications in renal transplant patients. Methods: …A total of 33 renal transplant recipients with elevated kidney function parameters with initial diagnostic imaging between 2006 and 2017 were included in the study. The imaging studies and clinical data were analysed retrospectively. The diagnostic accuracy of CEUS was compared to CT, DSA and renal scintigraphy respectively which are classified as gold standard for diagnosis of vascular complications in renal transplant patients. Out of 23 patients 15 patients showed vascular complications in CT, DSA or radioisotope renography and in 15 out of 15 patients CEUS detected the vascular complication. RESULTS: CEUS showed a sensitivity of 100%, a specificity of 66.7%, a positive predictive value (PPV) of 71.4%, and a negative predictive value (NPV) of 100%. CONCLUSIONS: CEUS is a non-nephrotoxic and safe method for the initial imaging of vascular complications in renal transplant recipients. Compared to the gold standard imaging modalities CT, DSA and radioisotope renography CEUS shows a high sensitivity and NPV in detecting vascular complications. In cases with suspected stenosis of the transplant renal artery additional DSA might be needed. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, CT, DSA, renal transplant, vascular complications

DOI: 10.3233/CH-179221

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 407-413, 2017

Authors: Putz, Franz Josef | Hautmann, Matthias G. | Banas, Miriam C. | Jung, Ernst Michael

Article Type: Research Article

Abstract: BACKGROUND: The plantar fasciitis is a common disease with a high prevalence in public and a frequent cause of heel pain. OBJECTIVE: In our pilot study, we wanted to characterise the feasibility of shear-wave elastography and contrast-enhanced ultrasound (CEUS) in the assessment of the plantar fasciitis. METHODS: 23 cases of painful heels were examined by B-Mode ultrasound, Power Doppler (PD), shear wave elastography and contrast-enhanced ultrasound before anti-inflammatory radiation. Time-intensity-curves were analysed by the integrated software. The results for area-under-the-curve (AUC), peak, time-to-peak (TTP) and mean-transit-time (MTT) were compared between the plantar fascia and the surrounding …tissue. RESULTS: All cases showed thickening of the plantar fascia, in most cases with interstitial oedema (87.0%). Shear wave elastography showed inhomogeneous stiffness of the plantar fascia. 83.3% of cases showed a visible hyperperfusion in CEUS at the proximal plantar fascia in comparison to the surrounding tissue. This hyperperfusion could also be found in 75.0% of cases with no signs of vascularisation in PD. AUC (p  = 0.0005) and peak (p  = 0.037) were significantely higher in the plantar fascia than in the surrounding tissue. CONCLUSION: CEUS and shear wave elastography are new diagnostic tools in the assessment of plantar fasciitis and can provide quantitative parameters for monitoring therapy. Show more

Keywords: CEUS, plantar fasciitis, shear wave elastography, TIC-Analysis

DOI: 10.3233/CH-179222

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 415-423, 2017

Authors: Zengel, Pamela | Notter, Florian | Reichel, Christoph A. | Clevert, Dirk A.

Article Type: Research Article

Abstract: BACKGROUND: It is difficult to assess tumors of the parotid gland preoperatively. However, it is essential for the surgeon to know which kind of tumor is present. Ultrasound is the method of choice, but there is still no reliable differential diagnostic tool for determining whether a tumor is malignant or benign. OBJECTIVE: The aim of our study was to examine the value of Virtual Touch imaging quantification (VTIQ) elastograpy in distinguishing between malignant and benign tumors as well as in identifying the most common benign tumor types. METHODS: The parenchyma of 100 parotid glands and 12 …lymph nodes of healthy volunteers and 50 tumors of the parotid gland were analyzed via ultrasound, color Doppler ultrasound, and VTIQ, and the results were then compared with histopathology. RESULTS: In comparison with benign tumors, in malignant tumors the tumor border was diffuse, the perfusion higher, and the VTIQ quality much lower. Share wave velocity of the user-defined region of interest was more frequently higher than 6.8 m/s in malignant tumors in comparison to benign tumors. CONCLUSIONS: VTIQ in combination with ultrasound examination provides additional information for distinguishing between benign and malignant tumors and shows promise for integration into preexisting ultrasound protocols. Show more

Keywords: Parotid tumors, ultrasound, elastography, ARFI imaging, Virtual Touch IQ, pleomorphic adenoma

DOI: 10.3233/CH-179223

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 425-434, 2017

Authors: Kehrer, Andreas | Mandlik, Veronika | Taeger, Christian | Geis, Sebastian | Prantl, Lukas | Jung, Ernst-Michael

Article Type: Research Article

Abstract: BACKGROUND AND OBJECTIVES: Facial paralysis causes excruciating impairments including facial asymmetry, limited eye closure, oral incontinence and social dysfunction. Modern plastic surgical reconstructions render favorable results with well-perfused dynamic muscle flaps. Post-operative tissue monitoring is a critical determinant for success. Contrast-enhanced Ultrasound (CEUS) and elastography have proven superior properties to evaluate tissue perfusion in various organs. We evaluated their role for functional muscle flaps positioned at the sub-skin level in facial palsy patients. METHODS: From 2016–2017 five patients received muscle flap reconstructions. Flaps included four free transplants and one pedicled transfer. Postoperatively tissue vitality and blood flow were …assessed with CEUS. One experienced examiner using linear probes (6–9, 6–15 MHz) and bolus injections of Sulphur-hexafluoride microbubbles evaluated tissue perfusion. Using the time intensity curve- (TIC)-analysis measurements were recorded for TTP (time to peak) and AUC (Area under curve). Tissue elasticity was assessed with ultrasound elastography. RESULTS: All flaps were successful and showed no major complications. TTP-values in flap tissue showed slightly decreased values of 35.12±33.99 s and 25.04±10.86 s compared to surrounding tissue with 19.88±6.94 s. AUC-analysis however revealed higher values of 292.25±169.52 RU and 274.51±115.88 RU than surrounding tissue with 150.90±40.21 RU. Elastography demonstrated predominantly elastic flap tissue whereas surrounding tissue confirmed a slightly harder tissue quality. CEUS in combination with elastography verified tissue vitality and blood flow in a safe and reproducible manner. CONCLUSIONS: Post-operative perfusion monitoring in muscle flaps positioned at a sub-skin level may be performed superiorly by CEUS and elastography in a quick, reproducible and minimally-invasive fashion. Show more

Keywords: Facial paralysis, functional muscle flaps, contrast-enhanced ultrasound (CEUS), elastography, tissue perfusion monitoring, blood flow

DOI: 10.3233/CH-179224

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 435-444, 2017

Authors: Bruenn, K. | Beyer, L. | Haimerl, M. | Pregler, B. | Stroszczynski, C. | Jung, E.M. | Wiggermann, P.

Article Type: Research Article

Abstract: OBJECTIVE: To compare contrast-enhanced computed tomography (CT) and contrast-enhanced ultrasound (CEUS) for the quantitative evaluation of an ablation defect following radiofrequency ablation of malignant liver lesions in a prospective study. MATERIALS AND METHODS: 22 radiofrequency ablations of malignant liver tumors were performed. The ablation defects were then measured and evaluated by two independent examiners via contrast-enhanced computed tomography (CT) and contrast-enhanced ultrasound (CEUS) using a 1–5 MHz multifrequency convex ultrasound transducer (LOGIQ E9, GE) with respect to the short-axis diameter, the long-axis diameter, and the area. RESULTS: Quantitative evaluation of ablation defects is possible with both contrast-enhanced …CT and CEUS. The average long-axis diameter was 47.1 mm (±11.08;±23,5%) on CEUS and 56.48 mm (±14.14;±25,0%) on CT; the short-axis diameter was 39.72 mm (±11.14;±28,05%) on CEUS and 40.27 mm (±10.50;±26,07%) on CT; the area was 1439.82 mm2 (±678.57;±47,13%) on CEUS and 2392.68 mm2 (1147.67;±48,0%) on CT. On average, ablation defects are assessed to be larger on CT than on CEUS. A significant correlation between the modalities could not be achieved for all measurement axes. CONCLUSION: CEUS can be used for the postinterventional detection and evaluation of ablation defects. However, these are always assessed to be larger on contrast-enhanced CT than CEUS. Show more

Keywords: CEUS, CT, ablation, RFA, HCC

DOI: 10.3233/CH-179225

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 445-451, 2017

Authors: Kauffmann, P. | Troeltzsch, M. | Cordesmeyer, R. | Heidekrueger, P.I. | Schliephake, H. | Canis, M. | Wolff, H.A. | Rave-Fraenk, M. | Stroebel, P. | Kehrer, A. | Prantl, L. | Aung, T.

Article Type: Research Article

Abstract: The chorioallantoic membrane of fertilized chicken eggs in an early phase of breeding presents an approved test situation for the growth and treatment of human cancer cells. These models work due to the inoculation of cells into the membrane that stays within the egg shell during the time of investigation. In this study a modification of this model is presented. Samples of native tumors, rather than cell lines, are transplanted into the membrane and the body of the egg is taken out of the shell and placed in a plastic bowl. These modifications lead to an enhanced accessibility to …the chorioallantoic membrane and the surrounding vessels thus facilitating intra venous access and application of pharmaceuticals and a focused radiotherapy. With the current modifications the embryo was kept alive and additionally, the vascularized tumor environment was preserved. Show more

DOI: 10.3233/CH-179226

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 453-457, 2017

Authors: Heine, Norbert | Koch, Christoph | Brebant, Vanessa | Kehrer, Andreas | Anker, Alexandra | Prantl, Lukas

Article Type: Research Article

Abstract: BACKGROUND: Breast Carcinoma is the most common malign tumor disease in women. 20–30% of these tumors have to be treated by removing all of the breast tissue. After that kind of therapeutic procedure, most of the women are severely traumatized and ask for reconstruction. The goldstandard of breast reconstruction is the free perforator flap from the lower abdomen (DIEAP-flap), which can provide body-own tissue and natural shape for the reconstructed breast. Many studies evaluate the shape of the reconstructed breast but neglect the skin sensitivity. Claim of this study was to compare this important part of reconstruction on two different …techniques of mastectomy. OBJECTIVE: In this retrospective study we evaluated which technique of mastectomy and breast reconstruction with DIEAP-Flap offers the highest outcome for sensibility of the reconstructed breast. Skin sparing mastectomy was compared with conventional mastectomy and the results of skin sensitivity were measured. METHODS: Ten patients underwent breast reconstruction with free abdominal perforator flap between 2011 and 2015 after conventional mastectomy (CM) and were compared with ten patients, who had a skin sparing mastectomy (SSM) with immediate reconstruction by DIEAP-flap during the same time interval. These two groups were matched by age, height, weight and the time between reconstruction and examination. The sensitivity of the skin was measured by Semmes-Weinstein-Filaments in the strength beginning from 0,07 g till 300 g for deep sensation. The logarithmic profile of these measurements had been transferred into a continuous data system beginning from 1 point, which stands for no sensation, till 7 points for pressure threshold of 0,07 g. RESULTS: Patients who underwent DIEAP-reconstruction after skin sparing mastectomy showed a higher sensation at all regions of the new breast in comparison to reconstruction after conventional mastectomy, beginning from the nipple to the areola and the breast skin. The results in the CM-group were 1.0 points at the mamilla, 1.33 pts. at the areola and 1.78 pts. at the breast skin. In the SSM-group, the findings were 3 pts. at the mamilla, 3.25 pts. at the areola and 5.25 pts. at the breast skin. CONCLUSION: The skin sparing mastectomy combined with immediate reconstruction by DIEAP-flap provides an excellent therapeutic option for patients, who are suitable for this technique, which takes into account not only the form but also the sensitivity of the breast. Show more

Keywords: Breast reconstruction, DIEP, skin sensation, breast cancer, skin sparing mastectomy

DOI: 10.3233/CH-179227

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 459-465, 2017

Authors: Daeschlein, Georg | Langner, Inga | Wild, Thomas | von Podewils, Sebastian | Sicher, Claudia | Kiefer, Thomas | Jünger, Michael

Article Type: Research Article

Abstract: Monitoring of perfusion is a cornerstone in surgery, phlebology and basic science to proof wound healing by interventions. In chronic wound management it is of utmost importance to realize and parametrize wound bed perfusion to verify actual, and plan further treatment by noninvasive diagnostics. Up to now monitoring is based on visual inspection of wounds as conventionally practiced over more than decades. The main problems of visual inspection are the lack of standardization and comparability because of interindividual variations. Therefore technical performance with contact free probes based on standardized perfusion measuring is strongly needed. Hyperspectral imaging (HSI) was investigated to …overcome manual and visual wound inspection in monitoring of wound healing. HSI works noninvasive, and imaging of relevant perfusion parameters is possible without the need of contrast enhancing drugs. METHODS: HSI technology uses imaging spectroscopic analysis in visual and near infrared spectrum to get information on imaged tissue in less than 10 s. Tissue is radiated by broad spectrum light and the following parameters are calculated from remitted spectra: the grade of oxygenation and the volume proportion of hemoglobin (in superficial and also deeper (8 mm) tissues. The calculated data comprise the “Tissue hemoglobin oxygen saturation” (StO2 ) as percental oxygenation index to assess superficial perfusion (VIS-spectrum), the “Near infrared perfusion” (NIR) to assess deeper perfusion (near infrared spectrum) and the “Tissue hemoglobin index” (THI) to measure the percental volume of hemoglobin of surface perfusion (VIS-spectrum). The measurements of these parameters are calculated as false color-coded perfusion results on screen. We investigated different kind of wounds (combustion, infection, ulcer wounds, wounds in immune disorders, trauma wounds) determining superficial and deeper oxygen saturation, hemoglobin distribution and water content using hyperspectral imaging with TIVITA™ Tissue system. RESULTS: Hyperspectral Imaging allowed easy real time determination and visualization of hemodynamically relevant parameters- superficial and deeper oxygen saturation, total hemoglobin and tissue water content. In the patient with scleroderma, acral lesions with decreased perfusion correlated well with necrotic skin aspects. HSI clearly revealed macroscopic conspicuous suture wounds after Dupuytren surgery, infected soft tissue wounds with strong inflammatory hyperemia, edema in burn injuries, spatial geometry of abscess formation and chronic ulcer wounds. All measurements influenced further surveillance decisions. Hyperspectral imaging seems suitable for routine diagnostics and monitoring of skin and soft tissue lesions like acute and chronic wounds. It allows surveillance of postoperative suture wounds and burn wounds. Special indications may be transplant surveillance and monitoring of therapeutical interventions. Show more

Keywords: Hemodynamic alteration, microcirculation, oxygen saturation, wound healing, wound medicine

DOI: 10.3233/CH-179228

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 467-474, 2017

Authors: Braun, Diana | Dietze, Stefanie | Pahlitzsch, Tamara M.J. | Wennysia, Inggrid C. | Persson, Pontus B. | Ludwig, Marion | Patzak, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Descending vasa recta (DVR) supply the inner part of outer renal medulla an area at risk for hypoxic damages. OBJECTIVE: We hypothesize increased vasoreactivity after hypoxia/re-oxygenation (H/R) in DVR, which might contribute to the reduced medullary perfusion after an ischemic event. METHODS: Live kidney slices (200μ m) from SD rats were used for functional experiments. TUNEL assay and H&E staining were used to estimate slice viability. Kidney slices were treated with carbogen or hypoxia (1% O2 ) for 60 or 90 min and vasoreactivity to Ang II (10–7 M) was recorded by DIC microscopy after …re-oxygenation with carbogen. Expression of NOS and NADPH enzymes mRNA were determined in iron-perfusion isolated VR. RESULTS: Percentage of apoptotic cells increased in control and H/R after 90 min in the medulla. Ang II– induced constriction of DVR was reduced after 90 min in control (compared to 60 min), but not after H/R. NOS enzymes mRNA expression levels decreased over 90 min hypoxia. CONCLUSIONS: Increased reactivity of DVR to Ang II after H/R compared to control (90 min) suggest a role of DVR in renal ischemia/reperfusion injury. Show more

Keywords: Vasa recta, acute kidney injury, live kidney slices, hypoxia

DOI: 10.3233/CH-179230

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 475-484, 2017

Article Type: Other

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 485-485, 2017

Authors: Lehmann, Christian

Article Type: Editorial

DOI: 10.3233/CH-179231

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 487-488, 2017

Authors: Sharawy, Nivin | Mukhtar, Ahmed | Islam, Sufia | Mahrous, Reham | Mohamed, Hassan | Ali, Mohamed | Hakeem, Amr A. | Hossny, Osama | Refaa, Amera | Saka, Ahmed | Cerny, Vladimir | Whynot, Sara | George, Ronald B. | Lehmann, Christian

Article Type: Research Article

Abstract: INTRODUCTION: The outcome of patients in septic shock has been shown to be related to changes within the microcirculation. Modern imaging technologies are available to generate high resolution video recordings of the microcirculation in humans. However, evaluation of the microcirculation is not yet implemented in the routine clinical monitoring of critically ill patients. This is mainly due to large amount of time and user interaction required by the current video analysis software. The aim of this study was to validate a newly developed automated method (CCTools® ) for microcirculatory analysis of sublingual capillary perfusion in septic patients in comparison to …standard semi-automated software (AVA3® ). METHODS: 204 videos from 47 patients were recorded using incident dark field (IDF) imaging. Total vessel density (TVD), proportion of perfused vessels (PPV), perfused vessel density (PVD), microvascular flow index (MFI) and heterogeneity index (HI) were measured using AVA3® and CCTools® . RESULTS: Significant differences between the numeric results obtained by the two different software packages were observed. The values for TVD, PVD and MFI were statistically related though. CONCLUSION: The automated software technique successes to show septic shock induced microcirculation alterations in near real time. However, we found wide degrees of agreement between AVA3® and CCTools® values due to several technical factors that should be considered in the future studies. Show more

Keywords: Sublingual microcirculation, sepsis, shock, capillary perfusion, incident dark field imaging

DOI: 10.3233/CH-179232

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 489-498, 2017

Authors: Cerny, Vladimir | Astapenko, David | Burkovskiy, Ian | Hyspler, Radomir | Ticha, Alena | Trevors, Mary Ann | Lehmann, Christian

Article Type: Research Article

Abstract: The endothelial glycocalyx (EG) lining the endoluminal surface of the capillaries has been proposed as a key component of the microcirculation and a major player in microvascular pathology. Recent advances in the understanding of its physiological role and clinical significance have been made upon the development of methods allowing EG assessment in clinical medicine. Laboratory methods can assess the amount of EG damage by measuring levels of its degradation products (e.g. syndecan-1, heparan sulphate and hyaluronan sulphate), mostly in the plasma, however, their physiological turnover disqualifies them from being the reliable index of EG damage. At the bedside, in vivo video …microscopy tools technologies (e.g. Side-stream Dark Field imaging technology) allow indirect assessment of EG thickness in sublingual microcirculation by measuring the penetration extent (called Perfused Boundary Region) of flowing red blood cells into the EG. Show more

Keywords: Endothelial glycocalyx, laboratory methods, videomicroscopy, Perfused Boundary Region

DOI: 10.3233/CH-179235

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 499-503, 2017

Authors: Henzler, Dietrich | Scheffler, Matthias | Westheider, Arne | Köhler, Thomas

Article Type: Research Article

Abstract: BACKGROUND: In patients with shock, inflammation and sepsis alterations in microcirculation are common problems. Although the pathophysiologic consequences are well understood, measurements of microcirculation have not entered clinical routine so far. OBJECTIVE: To characterize the requirements for clinical microcirculation measurement techniques and the barriers for implementation into routine practice. METHODS: Clinical review of reliability, reproducibility, validity, availability and usefulness of clinically available measurement techniques to be used in patients with sepsis or cardiac surgery with cardiopulmonary bypass. RESULTS: Few methods such as video microscopy are readily available at the bedside, but are hampered by …the high variability of measurements and the lack of reliable automated software analysis. The correlation of microcirculation impairment measured by in-vivo microscopy with fatal outcomes has been established, but no recommendations have been given which parameters should be targeted to improve outcomes. Measurement of regional brain tissue oxygenation has been recommended for cardiac surgery, but does not specifically target microcirculation. CONCLUSIONS: International guidelines for the management of sepsis or cardiac anesthesia do not recommend specific goals targeting the microcirculation directly, but global hemodynamics. The reason for this may be attributed to the lack of methods that fulfill the requirements necessary to be clinically acceptable. Once the validity, i.e. any improvement in patient’s outcomes attributable to microcirculation measurements, can be established, clinical measurement of microcirculation could become part of routine treatment of patients with sepsis, inflammation and shock. Until then, more clinical studies targeting microcirculation are urgently needed. Show more

Keywords: Sepsis, shock, microcirculation, technology, in-vivo microscopy, cardiac anesthesia, inflammation

DOI: 10.3233/CH-179229

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 505-509, 2017

Authors: Kern, Hartmut | Sharawy, Nivin | Sardinha, Joel | Lehmann, Christian

Article Type: Research Article

Abstract: Community hospitals provide ideal conditions for large clinical studies because of the high volume of unselected patients admitted every year. With regard to microcirculatory studies, there are still some feasibility problems which are not solved yet. First of all, the lack of reliable automated software to analyze microcirculatory images represents the most important issue. Secondly, hardware aspects still need improvements regarding portability and miniaturization. Finally, to conduct studies of the microcirculation in a community hospital is also always a funding issue. The cost of the measurement device is hereby only one factor. Main cost factor is the personnel.

DOI: 10.3233/CH-179233

Citation: Clinical Hemorheology and Microcirculation, vol. 67, no. 3-4, pp. 511-514, 2017