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