Clinical Hemorheology and Microcirculation - Volume 72, issue 2

Authors: Jung, Friedrich | Connes, Philippe | Lehmann, Christian

Article Type: Editorial

DOI: 10.3233/CH-199008

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 117-118, 2019

Authors: Cheung, A.T.W. | Chen, P.C.Y. | Wong, K.Y. | Banerjee, A. | Tracy, B.D. | To, W.J.

Article Type: Research Article

Abstract: Orthokeratology (Ortho-K) is an over-night hard contact lens therapy, which physically reshapes the corneal curvature in order to stabilize or temporally eliminate myopia in patients. We hypothesize that the prolonged physical contact and mechanical pressure induced by the Ortho-K lenses may create lasting inadvertent effects and damages (microangiopathy), and may bring about unwanted changes in the microvasculature of the bulbar conjunctiva. Computer-assisted intravital microscopy (CAIM) was used to view, document (via videotaping) and objectively quantify (via computer-assisted image analysis) the real-time dynamic and morphometric characteristics of the conjunctival microcirculation in long-term (at least over one year) Ortho-K patients (n  = 11) …and matched non-user control subjects (n  = 8). Ortho-K patients were instructed to wear their lenses overnight following standard protocol. During the study, the conjunctival microcirculation of the left eye of all Ortho-K lens users was viewed, frequently re-focused and videotaped, without and with the lens in place, as outlined in Methods. The matched control subjects (non-lens wearing) were videotaped and studied in like manner. The dynamic and morphometric characteristics of each user and control subject were analyzed, quantified and summated as a severity index (SI) collectively for comparison. SI of Ortho-K lens users (4.18±1.08) differed significantly from SI of control subjects (1.75±1.39, p ≤0.05). In addition, changes in the conjunctival microcirculation (e.g., flow velocity, vessel diameter, shape change, etc) were viewed and videotaped immediately after the myopic patients put on the Ortho-K lenses. Eight of the 11 Ortho-K lens users displayed significant percentage changes (p ≤0.05) in flow velocity and 10 of 11 displayed significant percentage changes (p ≤0.05) in vessel diameter, without and with the Ortho-K lenses. The results clearly indicated that significant microvascular changes via tissue remodeling occurred, and were caused directly by the physical presence of the Ortho-K lenses. Show more

Keywords: Computer-assisted Intravital Microscopy (CAIM), Orthokeratology (Ortho-K), microcirculation, bulbar conjunctiva, microangiopathy

DOI: 10.3233/CH-189908

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 119-128, 2019

Authors: Zhu, Yi-Cheng | Zhang, Yuan | Deng, Shu-Hao | Jiang, Quan | Shi, Xiu-Rong | Feng, Ling-Ling

Article Type: Research Article

Abstract: BACKGROUND: Plasma cell mastitis (PCM), a common type of mastitis often mimics malignancy clinically and radiologically. OBJECTIVE: The study was designed to explore the diagnostic value of superb microvascular imaging (SMI) in differentiating PCM from malignant breast lesions. METHODS: A total of 95 breast lesions underwent conventional ultrasound (US) and SMI examination between May 2016 and April 2018. Vessels were detected in SMI in a quantitative manner. Blood flow parameters including systolic peak velocity (SPV), resistance index (RI), and pulsatility index (PI) were evaluated. We further assessed the diagnostic performances of US and US+SMI. …RESULTS: The majority of PCM were in regular shape and displayed no calcification compared with malignant breast lesions. Regarding blood flow parameters, PCM obtained significantly lower mean value of RI and PI compared with malignant lesions (P  < 0.05). The sensitivity, specificity and accuracy rate of US+SMI (84.62%, 76.47%, 83.16%) was significantly higher than those of US (78.21%, 64.71%, 75.59%). CONCLUSIONS: The present study supports that SMI is a novel ultrasound technology in revealing micro-vessels in breast lesions. The combined modality of US+SMI presented a better diagnostic performance in making a distinction between PCM and malignant breast carcinomas. Show more

DOI: 10.3233/CH-180468

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 129-138, 2019

Authors: Renno, Isabell | Boos, Anja M. | Horch, Raymund E. | Ludolph, Ingo

Article Type: Research Article

Abstract: BACKGROUND: Negative pressure wound therapy applied over closed incisions (ciNPT) has been shown to influence wound healing. Therefore, the aim of this study was to examine the short-term effects of ciNPT on skin perfusion patterns in postbariatric wounds. METHODS: 17 patients were included. Patients from the study group received a ciNPT dressing with a continuous negative pressure of – 125 mmHg for five days. Two intra- and two postoperative measurements were performed using both a combined laser Doppler spectrophotometry and an ICG angiography system to determine oxygen saturation (sO2), hemoglobin content (rHb) and perfusion patterns. RESULTS: Three …days postoperatively the sO2 was significantly higher in the study group compared to the control group and also compared to the end of the operation. Concerning the rHb, there was no statistical significant alteration in or between the groups, but a trend towards a correlated alteration of sO2 and rHb. ICG angiography showed an earlier and stronger enhancement of perfusion parameters in the study group. CONCLUSION: CiNPT has a positive effect on oxygen saturation and tissue perfusion, which are both associated with the wound healing process. The use of ciNPT could therefore possibly reduce the risk of wound healing complications in this high-risk patient group. Show more

Keywords: Skin perfusion patterns, combined laser Doppler spectrophotometry, ICG angiography, oxygen saturation, relative hemoglobin content, wound healing, O2C, SPY, weight loss, obesity, maintenance of weight loss, body contouring surgery, abdominoplasty, postoperative complications, closed incisional negative pressure wound therapy, ciNPWT, ciNPT, NPWT, postbariatric surgery, postoperative wound care, high-risk patients

DOI: 10.3233/CH-180450

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 139-150, 2019

Authors: Guo, Le-Hang | Wang, Dan | Li, Xiao-Long | Liu, Bo-Ji | Chen, Shigao | Li, Dan-Dan | Xu, Hui-Xiong

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the stiffness distribution in the ablated zone after radiofrequency ablation (RFA), we used a device called tissue elastometer based on gross liver samples. MATERIALS: AND METHODS: Twelve freshly excised porcine livers were subject to RFA under a same setup to form elliptic ablated samples. Each sample was cut open for gross examination, and then the surface of the section plane was sliced into one piece for Young’s modulus test using the tissue elastometer. Five test points along the long- and short-axis on each piece were selected to evaluate stiffness distribution respectively. Among them, …four points distributed equidistantly from center to boundary in the ablated zone and one was in the unablated zone. RESULTS: In the ablated zone, we found the Young’s moduli were significantly different among the four test points both in long- (F = 99.04, p <0.001) and short-axis (F = 79.47, p <0.001) directions. The Young’s modulus showed a downtrend in each direction, and was linearly related to the distance from the center to the test point (for long axis, R2 = 0.968; for short axis, R2 = 0.984, both p <0.001). A more significant downtrend was observed in short-axis direction. The Young’s moduli gained from the inner edge of ablated zone were comparable and significantly higher than those from the outer edge for both directions. The maximum value of 24.71kPa for Young’s modulus was the appropriate threshold to ensure the tissues were necrotic completely. CONCLUSION: The stiffness inside the ablated zone represented a radial distribution with downtrend, following a linear law. The stiffness at the inner edge of ablated zone is stable and significantly higher than that at the outer edge. The maximum value of 24.71 kPa close to the inner edge of Wz may be used as the standard of complete ablation. Show more

Keywords: Stiffness distribution, radiofrequency ablation, tissue elastometer, Young’s modulus

DOI: 10.3233/CH-180404

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 151-160, 2019

Authors: Hahn, Robert G. | Hasselgren, Emma | Björne, Håkan | Zdolsek, Markus | Zdolsek, Joachim

Article Type: Research Article

Abstract: BACKGROUND: Injury (shedding) of the endothelial glycocalyx layer, which alters local blood flow and microvascular permeability, is assessed by measuring components of this layer in circulating blood. The influence of renal function on their concentrations is unknown. METHODS: Plasma and urine concentrations of three shedding products (syndecan-1, hyaluronic acid, and heparan sulfate) and creatinine were measured over 5 hours in 15 healthy volunteers and 15 postoperative patients; this guaranteed a spread of kidney functions. Renal clearances were calculated. RESULTS: Low renal clearances of syndecan-1 (mean 3.5 mL/min) and hyaluronic acid (0.8 mL/min) correlated inversely with the 6-fold variability …in the plasma concentrations of these substances (r  = – 0.45 and– 0.49). Low creatinine clearance correlated inversely (r  = – 0.60) and plasma creatinine directly (r  = 0.52) with the two-fold variability in heparan sulfate, which was the only shedding substance that also correlated with C-reactive protein (r  = 0.51) and, therefore, showed higher concentrations after surgery. CONCLUSIONS: The present explorative study suggests that a 6-fold variability in the plasma concentrations of three commonly measured endothelial shedding products can be understood by the kidney’s ability to excrete them. This finding has implications when interpreting results of studies where shedding is assessed. Show more

Keywords: Endothelial glycocalyx, syndecan-1, heparan sulfate, hyaluronic acid, kidney function, renal clearance

DOI: 10.3233/CH-180444

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 161-168, 2019

Authors: Li, H. | Ding, X. | Lu, L. | Yang, J. | Ma, J.

Article Type: Research Article

Abstract: PURPOSE: To explore the normal morphological features of the retinal periarteral capillary free zone (paCFZ) and the changes associated with severe non-proliferative diabetic retinopathy (NPDR) by optical coherence tomography angiography (OCTA). METHODS: A total of 148 normal subjects and 115 patients with severe NPDR were enrolled. Spectral-domain OCTA was used to acquire the image with a Cirrus prototype. Diameter and area of each paCFZ quadrant and adjacent large artery diameter was estimated. RESULTS: In healthy subjects, the maximum width of paCFZ in the temporal quadrant (169.38 ± 19.26 μ m) was smaller than the other three quadrants …(all P <0.001). The ratio of maximum paCFZ width to artery caliber was much larger in the nasal quadrants than the rest quadrants (Ps <0.05). In patients with severe NPDR, both maximum width and area of paCFZ were significant larger, and the retinal artery inner diameters significant smaller in each quadrant compared to normal subjects (Ps <0.05). The ratio of paCFZ maximum width to artery caliber maximum width was significant greater, and the ratio of paCFZ area to artery caliber was significantly higher in all quadrants compared to normal eyes (Ps <0.05). CONCLUSIONS: OCTA provides noninvasive and quantitative measurement of paCFZ dimensions. The maximum width and area of paCFZ quadrants and the ratios of these parameters to adjacent inner artery width and area are elevated in severe NPDR, suggesting that changes in paCFZ dimension can be used as clinical indices for diseases associated with changes in retinal microcirculation and oxygen pressure. PRÉCIS: Optical coherence tomography angiography revealed differences in retinal periarteral capillary free zone (paCFZ) morphometry between health retina and severe non-proliferative diabetic retinopathy. Morphometric indices of paCFZ may be useful for monitoring disease occurrence and progression. Show more

Keywords: Non-proliferative diabetic retinopathy, periarteral capillary free zone, optical coherence tomography angiography

DOI: 10.3233/CH-180458

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 169-178, 2019

Authors: Lee, Chang Youn | Lee, Jiyun | Seo, Hyang-Hee | Shin, Sunhye | Kim, Sang Woo | Lee, Seahyoung | Lim, Soyeon | Hwang, Ki-Chul

Article Type: Research Article

Abstract: BACKGROUND: Cardiac hypertrophy is an important risk factor for heart failure. The MEK-ERK axis has been reported as a major regulator in controlling cardiac hypertrophy. TAK733 is a potent and selective MEK inhibitor that suppresses cell growth in a broad range of cell lines. OBJECTIVE: Therefore, we aimed to investigate the anti-hypertrophic effect of TAK733 in cardiomyocytes. METHODS: Cardiomyocyte hypertrophy was induced with norepinephrine (NE) or phenylepinephrine (PE) using H9c2 cells. To confirm the cardiomyocyte hypertrophy, cell size and protein synthesis were measured and hypertrophy-related gene expression was estimated by reverse transcription polymerase chain reaction. To …identify the signaling pathway involved, immunoblot analysis were performed. RESULTS: We observed that NE activated MEK-ERK signaling and increased ANP and BNP expression, resulting in cardiomyocyte hypertrophy. TAK733 significantly reduced cardiomyocyte hypertrophy by regulating NE-induced ERK1/2 and ERKThr188 activation, hypertrophy marker expression, and cardiomyocyte hypertrophy through depression of MEK activity. In addition, we examined that PE-induced cardiomyocyte hypertrophy was also attenuated by TAK733. CONCLUSIONS: Here, we report that TAK733 suppressed NE- or PE-induced cardiomyocyte hypertrophy by repressing a crucial component of cardiac hypertrophy-related pathways. These results suggest that TAK733 may be a useful therapeutics for cardiac hypertrophy and warrants further in vivo studies. Show more

Keywords: Cardiac hypertrophy, MEK inhibitor, TAK733, norepinephrine

DOI: 10.3233/CH-180476

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 179-187, 2019

Authors: Bach, Annika | Hameister, Clarissa | Slowinski, Torsten | Jung, Ernst Michael | Thomas, Anke | Fischer, Thomas

Article Type: Research Article

Abstract: BACKGROUND: Besides mammography, breast ultrasound is the most important imaging modality for women with suspected breast cancer. New software tools bear high potential for improved detectability and specification of malignant breast lesions. OBJECTIVE: To compare the halo depicted around malignant breast lesions by ultrasound using Acoustic Structure Quantification (ASQ) of raw image data with the echogenic rim seen in B-mode ultrasound. METHODS: This retrospective study included 37 women for whom conventional B-mode ultrasound of the breast and ASQ were available as well as histopathology findings for comparison. Software tools were used to measure the halo area …or echogenic rim and tumor area and calculate halo-to-lesion ratios for the two ultrasound modes. Six inexperienced readers characterized the breast lesions based on this information. Specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. ANOVA, the Wilcoxon test, and ROC curve analysis were performed. RESULTS: There was a linear relationship between ASQ-based and B-mode-based halo-to-lesion ratios; however, a systematic error was also noted. ASQ-derived ratios tended to be higher for breast lesions with lymphangioinvasion (p  = 0.051, n.s.) and higher N-stages (p  > 0.925, n.s.), while there was no correlation with other markers. Because of the significantly greater conspicuity of peritumoral halos in the ASQ mode, inexperienced readers achieved greater sensitivity (78% vs. 74%) and specificity (75% vs. 71%) and higher NPVs (75% vs. 71%) and PPVs (78% vs. 74%) compared with B-mode images. Greater halo conspicuity affected the identification of malignant lesions with both modes; ASQ was found to be particularly well suited (FBimage (1,100) = 19.253, p  < 0.001; FASQ (1,100) = 52.338, p  < 0.001). The inexperienced readers were significantly more confident about their diagnosis using the ASQ maps (z = –3.023, p  = 0.003). CONCLUSIONS: We conclude that the halo in ASQ and the echogenic rim in B-mode ultrasound are attributable to different morphologic correlates. ASQ improves diagnostic accuracy and confidence of inexperienced examiners because of improved halo visibility. Show more

Keywords: Ultrasound, breast neoplasms, breast cancer, breast lesion, B mode, ASQ, sonography, diagnostic imaging, halo, peripheral rim, peripheral zone, BI-RADS

DOI: 10.3233/CH-180484

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 189-200, 2019

Authors: Zhang, Yi | Wu, Ruipeng | Gu, Cheng | Gao, Fulin | Hu, Xiaojuan | Zang, Peixi | Dong, Tong

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the role and potential mechanism of Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κ B) signaling pathway in cognitive impairment induced by cerebral small vascular disease (CSVD), so as to provide a reference for the clinical treatment of CSVD-induced cognitive impairment. METHODS: Mice with TLR4 gene knockout (n  = 20) and those with wild-type TLR4 gene (n  = 40) aged 8–10 weeks old were divided into blank control group (Control group, n  = 20), wild-type + CSVD group (WT + CSVD group, n  = 20) and TLR4 gene knockout + CSVD group (TLR4 KO + CSVD group, n  = 20). Allogeneic thrombosis (particle diameter: 50–70 mm) was injected …to the mouse’s external carotid artery to create a model of learning and memory dysfunction. Step-down test and Y-type maze test were utilized to examine the learning and memory abilities of the mice. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblotting techniques were adopted to measure the levels of apoptosis-related genes [B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), C-caspase-3 and T-caspase-3] in the brain tissues of mice. Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method was applied to detect the apoptosis of neuronal cells in the brain tissues. Meanwhile, the levels of oxidative stress markers, including superoxide dismutase (SOD), gp91 and malondialdehyde (MDA), were measured. Finally, the expression level of TLR4/NF-κ B pathway was detected. RESULTS: The latency in the step-down test in the WT + CSVD group was remarkably longer than that in the Control group, and the number of errors was evidently larger than that in the Control group (p  < 0.05). At the same time, in the WT + CSVD group, the expression levels of pro-apoptotic genes Bax and C-caspase-3 were up-regulated markedly, while the expression level of anti-apoptotic gene Bcl-2 declined notably (p  < 0.05). TUNEL results showed that the number of apoptotic cells in the brain tissues in the WT + CSVD group was about 12 times that in the Control group (p  < 0.05). Meanwhile, the SOD expression level was lowered, and the MDA expression level was elevated in the brain tissues in the WT + CSVD group. In addition, the TLR4/NF-κ B pathway was prominently activated in the mice in the WT + CSVD group (p  < 0.05). After TLR4 gene knockout, the cognitive functions of the mice were improved markedly, and the apoptosis of neuronal cells and oxidative stress in the brain tissues were suppressed significantly in the meantime. Moreover, the activation of the TLR4/NF-κ B signaling pathway was also inhibited. CONCLUSION: The TLR4/NF-κ B pathway is involved in the occurrence and development of CSVD-induced cognitive impairment through regulating oxidative stress and cell apoptosis. Show more

Keywords: TLR4/NF-κB, CSVD, cognitive impairment

DOI: 10.3233/CH-180515

Citation: Clinical Hemorheology and Microcirculation, vol. 72, no. 2, pp. 201-210, 2019