Clinical Hemorheology and Microcirculation - Volume 58, issue 1

Authors: Vayá, Amparo | Giménez, Cristina | Sarnago, Ana | Alba, Amparo | Rubio, Olaya | Hernández-Mijares, Antonio | Cámara, Rosa

Article Type: Research Article

Abstract: BACKGROUND: Subclinical hypothyroidism (SCH) has been suggested to be associated with increased cardiovascular risk by different mechanisms. Several cardiovascular risk factors have been analysed, but yielded controversial results. OBJECTIVES: We aimed to analyse whether there are differences in several cardiovascular risk markers, such as lipids, inflammatory parameters: plasma viscosity (PV), fibrinogen and C reactive protein (CRP); homocysteine (Hcy) and red blood cell distribution width (RDW), when comparing SCH and controls. We also analysed which of these parameters predict SCH risk and constitute independent markers. METHODS: We determined PV in a Fresenius capillary plasma viscosimeter, Hcy by a chemiluminiscent enzyme immunoassay, …and biochemical and haematological parameters by conventional laboratory methods in 58 SCH outpatients and 58 controls matched for age and gender. RESULTS: SCH patients did not show statistical differences for glucose, lipids or leucocytes (p > 0.05). However, patients showed a higher prevalence for use of hypolipidaemic drugs, body mass index (BMI), thyroid stimulating hormone (TSH), PV, CRP, fibrinogen, Hcy and RDW (p < 0.05). RDW correlated with inflammation parameters: PV (r = 0.331, p < 0.05), fibrinogen (r = 0.424, p < 0.05), CRP (r = 0.433, p < 0.01) and leucocytes (r = 0.613, p < 0.01). None of the cardiovascular markers correlated with the TSH levels (p > 0.05) In the unadjusted logistic regression analyses, BMI ≥28 kg/m2 , RDW ≥14%, Hcy ≥12 μm/L, fibrinogen ≥400 mg/dL and MCV ≤88 fL increased SCH risk, but only RDW ≥14% and fibrinogen ≥400 mg/dL independently increased this risk in the adjusted logistic regression analyses (OR = 4.68, 95% CI 1.20–18.30 P = 0.026; OR = 3.48, 95% CI 1.08–11.23 P = 0.037). CONCLUSION: SCH patients show a higher cardiovascular risk, characterised by increased PV, fibrinogen, Hcy and RDW. However, only fibrinogen ≥400 mg/dL and RDW ≥14% are independent predictors of SCH. Show more

Keywords: Subclinical hypothyroidism, red blood cell distribution width, homocysteine, fibrinogen, plasma viscosity, cardiovascular risk

DOI: 10.3233/CH-141871

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 1-7, 2014

Authors: Klein, S.M. | Prantl, L. | Geis, S. | Eisenmann-Klein, M. | Dolderer, J. | Felthaus, O. | Loibl, M. | Heine, N.

Article Type: Research Article

Abstract: BACKGROUND: Grafting of autologous lipoaspirate for various clinical applications has become a common procedure in clinical practice. With an estimated mortality rate of 10–15 percent, fat embolism is among the most severe complications to be expected after lipofilling therapies. OBJECTIVE: The aim of this study was to determine the level of interstitial pressure after the injection of defined volumes of lipoaspirate into the subcutaneous tissue of female breasts. It was hypothesized, that interstitial pressure levels exceed the physiologic capillary pressure during lipofilling procedures and hence increase the potential risk for fat embolism. Further it was investigated if external tissue expansion …has the potential to significantly reduce interstitial tissue pressure. METHODS: Interstitial pressure was monitored in 36 female patients, that underwent autologous fat injections into the breast. Measurements were conducted with a sensor needle connected to a pressure transducer (LogiCal Pressure Monitoring Kit, Smiths medical int. Ltd., UK). Patients were divided into 4 subcohorts differing in their pre-treatment regimen or local tissue conditions. Pre-treatment consisted of tissue expansion, achieved with the Brava™ (Brava LLC Miami, Fla., USA) vacuum-chamber. RESULTS: The increase in interstitial pressure after injection volumes of 100 ml (p = 0.006), 200 ml (p = 0.000) and between 100 ml and 200 ml (p = 0.004) respectively, were significant in non-mastectomized patients without pre-treatment. Patients pre-treated with Brava™ did not show such statistically significant differences in interstitial pressures before and after the injection of 100 ml and 200 ml of lipoaspirate (p = 0.178). The difference in interstitial pressure in mastectomized patients between 0 ml and 100 ml (p = 0.003), as well as 0 ml and 200 ml (p = 0.028) was significant. The difference in pressures between pre-treated patients and patients without pre-treatment did not differ significantly in the mastectomized patient cohort. CONCLUSION: During lipofilling procedures interstitial pressures are reached that exceed pressure limits defined as hazardous for fat embolism. To date it is unknown what pressure levels need to be considered critical for complications in soft tissue interventions. Further the results indicate higher interstitial pressures for patients that had undergone mastectomy, whereas pre-treatment with external tissue expansion seemed to diminish pressure values. Show more

Keywords: Lipofilling, pressure monitoring, Brava, fat embolism syndrome

DOI: 10.3233/CH-141872

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 9-17, 2014

Authors: Wang, Weiwei | Xu, Xun | Li, Zhengdong | Lendlein, Andreas | Ma, Nan

Article Type: Research Article

Abstract: Mesenchymal stem cells (MSCs) are an ideal cell source for tissue engineering and regenerative medicine as they possess self-renewal properties and multilineage differentiation potential. They can be isolated from various tissues and expanded easily through normal cell culture techniques. Genetic modifications of MSCs to further improve their therapeutic efficacy have been widely studied and extensively researched. Compared to viral gene delivery methods, non-viral methods generate less toxicity and immunogenicity and thus represent a promising and effective tool for the genetic engineering of MSCs. In the last decades, various non-viral gene delivery strategies have been developed and some of them have …been applied for MSC transfection. This paper gives an overview of the techniques, influencing factors and potential applications of non-viral methods used for the genetic engineering of MSCs. Show more

Keywords: Mesenchymal stem cells, regenerative medicine, non-viral gene delivery, transfection, lipoplex, polyplex

DOI: 10.3233/CH-141883

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 19-48, 2014

Authors: Franke, R.P. | Scharnweber, T. | Fuhrmann, R. | Mrowietz, C. | Wenzel, F. | Krüger, A. | Jung, F.

Article Type: Research Article

Abstract: Different radiographic contrast media (RCM) were shown to induce morphological changes of blood cells (e.g. erythrocytes or thrombocytes) and endothelial cells. The echinocytic shape change of erythrocytes, particularly, affords alterations of the membrane cytoskeleton. The cytoskeleton plays a crucial role for the shape and deformability of the red blood cell. Disruption of the interaction between components of the red blood cell membrane cytoskeleton may cause a loss of structural and functional integrity of the membrane. In this study band4.9 and actin as components of the cytoskeletal junctional complex were examined in human erythrocytes after suspension in autologous plasma or in …plasma RCM mixtures (30% v/v Iodixanol-320 or Iopromide-370) followed by a successive double staining with TRITC-/FITC-coupled monoclonal antibodies. After adding Iopromide-370 to the plasma in practically none of the cells the rounded conformation of the membrane cytoskeleton – as it appeared in cells suspended in autologous plasma – was found. In addition, Iopromide-370 induced thin lines and coarse knob-like structures of band4.9 at the cell periphery while most cell centers were devoid of band4.9, and a box-like arrangement of bands of band4.9. A dissociation between colours red (actin) and green (band4.9) occurred as well. In contrast, erythrocytes suspended in a plasma/Iodixanol-320 mixture showed a membrane cytoskeleton comparable to cells suspended in autologous plasma, Similar results were found with respect to the distribution of actin. This study revealed for the first time RCM-dependent differences in band4.9 activities as possible pathophysiological mechanism for the chemotoxicity of radiographic contrast media. Show more

Keywords: Radiographic contrast media, band4.9 Iodixanol-320, Iopromide-370, actin, chemotoxicity, cytoskeletal junctional complex, erythrocyte

DOI: 10.3233/CH-141894

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 49-63, 2014

Authors: Büttner, Petra | Galli, Roberta | Jannasch, Anett | Schnabel, Christian | Waldow, Thomas | Koch, Edmund

Article Type: Research Article

Abstract: Degenerative heart valve disease is a life-threatening disease affecting about 3% of the population over 65 years. Up to date, cardiac surgery with heart valve replacement is the only available therapy. The disease is characterized by degenerative disorganization of the heart valve structure and alterations in the residing cell populations. Causes and mechanisms of disease genesis are still not fully understood and until now pharmacological therapies are not available. Thus there is enormous interest in new technologies that enable a better characterization of structure and composition of diseased valves. Currently most research techniques demand for extensive processing of extracted valve …material. We present a novel approach combining coherent anti-Stokes Raman scattering, endogenous two-photon excited fluorescence and second harmonic generation. Cusp constituents can be examined simultaneously, three-dimensionally and without extensive manipulation of the sample enabling impressive insights into a complex disease. Show more

Keywords: Heart valve disease, aortic valve stenosis, aortic valve insufficiency, fibrosis, coherent anti-Stokes Raman scattering, endogenous two-photon excited fluorescence, second harmonic generation, nonlinear optical microscopy

DOI: 10.3233/CH-141882

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 65-75, 2014

Authors: Vahldiek, Janis L. | Lehmann, Kai S. | Poch, Franz | Zurbuchen, Urte | Kreis, Martin E. | Gemeinhardt, Ole | Hamm, B. | Niehues, Stefan M.

Article Type: Research Article

Abstract: Radiofrequency ablation (RFA) has shown to be a reasonable alternative for the treatment of hepatic tumors and metastases although multiple limitations remain. Cooling effects due to larger vessels can prevent complete coverage and may lead to early tumor relapse. This preliminary in vivo pig study combines the use of multipolar RFA with three applicators (six electrodes) and interrupted liver perfusion using Pringle's maneuver to overcome the most serious limitations. Furthermore, immediate detection of incomplete RFA is important to revise ablation. We used contrast enhanced computed tomography (CECT) to evaluate post ablation results in comparison to macroscopic images in healthy pig …liver. We found significantly (p = 0.001) larger ablation zones and no affection by larger vessels with interrupted liver perfusion. This allows effective RFA for larger tumors. Immediate postinterventional CECT provided comparable results (r = 0.985) to macroscopic evaluation. Show more

Keywords: Liver perfusion, animals, catheter ablation, electrodes, imaging, three-dimensional/*methods, multidetector computed tomography, radiography, Interventional/methods, *contrast media

DOI: 10.3233/CH-141886

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 77-87, 2014

Authors: Greis, C.

Article Type: Research Article

Abstract: Ultrasound contrast agents have substantially extended the clinical value of ultrasound, allowing the assessment of blood flow and distribution in real-time down to microcapillary level. Selective imaging of contrast agent signals requires a contrast-specific imaging mode on the ultrasound scanner, allowing real-time separation of tissue and contrast agent signals. The creation of a contrast image requires a specific interaction between the insonated ultrasound wave and the contrast agent microbubbles, leading to persistent oscillation of the bubbles. Several technical and procedural parameters have a significant influence on the quality of CEUS images and should be controlled carefully to obtain good image …quality and a reliable diagnosis. Achieving the proper balance between the respective parameters is a matter of technical knowledge and experience. Appropriate training and education should be mandatory for every investigator performing CEUS examinations. Show more

Keywords: Ultrasound, microbubble, contrast, CEUS, mechanical index, gain, frame rate, contrast agent dose, presets, image quality, artefacts

DOI: 10.3233/CH-141873

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 89-95, 2014

Authors: Nantais, Jordan | Dumbarton, Tristan C. | Farah, Nizam | Maxan, Alexander | Zhou, Juan | Minor, Samuel | Lehmann, Christian

Article Type: Research Article

Abstract: Methylene blue (MB) has been used with some success as a treatment for the vasoplegia of vasopressor-refractory septic shock. The putative mechanism of action of MB is the inhibition of endothelial nitric oxide within the microvasculature and improved responsiveness to endogenous catecholamines (norepinephrine (NE)). However, to date, no study has demonstrated the microcirculatory effect of methylene blue in septic shock. The objective of this randomized, controlled, animal study was to show, in an experimentally-induced, septic shock model in rats, the effects of MB and NE on global hemodynamics and the microcirculation. Mean arterial pressure (MAP) was drastically reduced following bacterial …endotoxin (lipopolysaccharide, LPS) administration in animals not receiving vasopressors. Only the combination of NE + MB restored MAP to control levels by the end of the three hour experiment. Intravital microscopy of the microcirculation was performed in the terminal ileum in order to examine functional capillary density in intestinal muscle layers and the mucosa, as well as leukocyte activation in venules (rolling, adhesion to the endothelium). Untreated LPS animals showed a significant increase in leukocyte adhesion and a decrease in capillary perfusion in the intestinal microcirculation. In groups receiving NE or NE+MB, we observed a significant decrease in leukocyte adhesion and improved functional capillary density, indicating that microvasculature function was improved. This study suggests that methylene blue may be able to improve hemodynamics while preserving microvascular function in septic shock. Show more

Keywords: Methylene blue, norepinephrine, septic shock, microcirculation, intravital imaging

DOI: 10.3233/CH-141874

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 97-105, 2014

Authors: Hiebl, B. | Hopperdietzel, C. | Hünigen, H. | Dietze, K. | Jung, F. | Niehues, S.M.

Article Type: Research Article

Abstract: Implantable long-term central venous port systems (CVPS) are widely used as a permanent means of accessing the vascular system for intravenous delivery of drugs, parenteral nutrition, blood transfusion, and blood sampling. These systems allow easy and repetitive puncture without causing much damage to the vessels. However, the body foreign surface of CVPS induces an inflammatory response with varying intensity (depending on the implant materials) that leads to formation of a fibrous tissue capsule around the implant. This study was designed to investigate the influence of bacterial infection on the tissue reaction induced by implanted CVPS in adult patients. 20 patients …(9 women, 11 men, 58 ± 14 yrs of age) were included in this study. These patients received explantation of a polysulfone based CVPS (ChemoSite™, Covidien, Mansfield, USA) due to port related infections (patients with bacterial infections at the implantation site: group A, 5 men, 1 women) or to other reasons such as termination of treatment, thrombosis, or CVPS dysfunction (patients without bacterial infections, group B, 6 men, 8 women) 299.9 ± 261.2 days after CVPS implantation. A sample of the encapsulating tissue covering the CVPS together with surrounding tissue (at least 1 × 1 cm2 ) was placed in a small container with fixing agent, a buffered neutral 4% formalin solution (pH 7). Histological sections of the samples were prepared for light microscopic analysis after paraffin embedding. Sections of 3 μm were cut and stained with haematoxylin and eosin, Weigert's elastic stain, and Heidenhain's azan stain. There was no difference in thickness, collagen and elastin content, or cell and capillary density of the fibrous capsule between both groups. Due to the wound healing reaction involving angiogenesis and fibroblast activation cell density and number of capillaries in the capsule tissue of all patients showed a positive correlation (r = 0.45, p < 0.05). However, the study demonstrated that at the end of the foreign body reaction the artificial tissue layer which covers the CVPS after implantation due to foreign body reaction shows only low reactivity towards infections. Show more

Keywords: Encapsulation, infection, central venous access system, biomaterial

DOI: 10.3233/CH-141881

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 107-113, 2014

Authors: Rjosk-Dendorfer, D. | Reu, S. | Deak, Z. | Hetterich, H. | Kolben, T. | Reiser, M. | Clevert, D.A.

Article Type: Research Article

Abstract: PURPOSE: To evaluate the use of color Doppler sonography and free hand sonoelastography in the assessment of breast fibroadenomas according to their size and shape. MATERIALS AND METHODS: From December 2012 to March 2013 women with 16 solid breast masses, classified as BI-RADS category 3 or 4 were examined with B-mode ultrasound, sonoelastography and color Doppler sonography. Lesions were subdivided according to their shape in round, ovoid or macrolobulated and according to their size (<2.0 cm or ≥2.0 cm). Two readers assessed sonoelastographic findings at 12.5 MHz using the tsukuba elasticity score and results of Doppler sonography using a score …of 0, 1 or 2, depending on the degree of perfusion. RESULTS: Among the 16 examined lesions 3 showed a round shape, 9 were ovoid and in 4 cases a macrolobulated appearance could be seen. No significant differences concerning Tsukuba-score depending on various shapes of fibroadenomas in B-mode sonography could be shown (p = 0.91) and also comparison of Tsukuba-scores and size of masses revealed no significant differences (p = 1.0). Sizes of fibroadenomas ≥2 cm were significantly associated with an increased vascularization of the lesions (p = 0.04) and a macrolobulated appearance in B-mode sonography (p = 0.04). CONCLUSION: The combination of color Doppler sonography and sonoelastography in addition to B-mode sonography leads to an increased accuracy in distinguishing benign from malignant breast masses and to an improvement in characterization of fibroadenomas independent of their shape or size. Show more

Keywords: Fibroadenoma, ultrasound, elastography, doppler sonography

DOI: 10.3233/CH-141884

Citation: Clinical Hemorheology and Microcirculation, vol. 58, no. 1, pp. 115-125, 2014