Clinical Hemorheology and Microcirculation - Volume 63, issue 4

Authors: Myung, Jeihak | Park, Seol Ju | Lim, Jaekwan | Kim, Yun Hee | Shin, Sehyun | Lim, Choon Hak

Article Type: Research Article

Abstract: The aim of this study was to evaluate changes in RBC aggregation and deformability over 24 hr and suggest specific shear stress values for detecting RBC deformability in a mouse endotoxemia model using lipopolysaccharide (LPS). Six-week-old male BALB/c mice received LPS (20 mg/kg) intraperitoneally. Aggregation indices (AIs) and T1/2 were measured to assess RBC aggregation, and elongation indices (EIs) were used to assess RBC deformability at shear stress values of 0.3, 0.5, 1, 3, 7, 10, 15 and 20 Pascals (Pa) 0, 30 min, 1, 2, 4, 6, 9, 12, 18 and 24 hours after the LPS injection. No …significant differences were detected in the AIs during the study period, however, T1/2 shortened significantly 2, 6, 12, 18, and 24 hr after the LPS injection. The EIs increased significantly 24 hr after LPS injection at 0.5 and 1 Pa shear stress, whereas it decreased significantly at 10 Pa of shear stress 24 hr after the LPS injection. Altered RBC deformability was detectable 24 hr after the LPS injection and T1/2 may be a sensitive marker for detecting changes in RBC aggregation. The EIs should be measured at 1 Pa to detect changes in RBC deformability in LPS-induced septic mice. Show more

Keywords: Lipopolysaccharide, RBC deformability, RBC aggregation, shear stress

DOI: 10.3233/CH-152017

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 305-312, 2016

Authors: Ergun, Dilek Duzgun | Karis, Denizhan | Alkan, Fatma Ates | Cakmak, Gulfidan | Yenigun, Mustafa | Ercan, Meltem

Article Type: Research Article

Abstract: BACKGROUND: Cigarette smoking deteriorates human health via vascular disorders, cancer and especially respiratory diseases. The aim of this study is to investigate effects of cigarette smoking on hemorheologic parameters, plasma osmolality and lung function in individuals without diagnosis of chronic obstructive pulmonary disease (COPD). METHODS: Patients diagnosed without COPD utilizing respiratory function test were enrolled in the study with three groups, ex-smokers (n  = 21), current-smokers (n  = 35) and never-smokers (n  = 43). Hemorheologic parameters and plasma osmolality were measured in hemorheology laboratory. SPSS 17.0 was used for statistical analysis. RESULTS: Blood and plasma viscosity, fibrinogen and …hematocrit levels, mean corpuscular volume and mean corpuscular hemoglobin concentration were significantly elevated in ex-smokers and current-smokers compared to never-smokers. The standardized red blood cell deformability and oxygen delivery index and lung function were statistically lower in current-smokers than never-smokers. Pulmonary blood flow rate was statistically lower in current-smokers and ex-smokers than never-smokers. Plasma osmolality was statistically significantly higher in ex-smokers and current-smokers than never-smokers. CONCLUSIONS: Our findings clearly show that cigarette smoking has severe effects on hemorheologic parameters, plasma osmolality and lung function even in individuals without COPD. Blood and plasma viscosity with plasma osmolality might be useful markers to detect early hemorheologic-hemodynamic alterations in cigarette smokers. Show more

Keywords: Cigarette smoking, blood viscosity, plasma viscosity, oxygen delivery index, red blood cell deformability, red blood cell aggregation, plasma osmolality, lung function

DOI: 10.3233/CH-152018

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 313-324, 2016

Authors: Wu, Qiong | Li, Yi | Wang, Yan

Article Type: Research Article

Abstract: OBJECTIVES: Our study sought to investigate the unique diagnostic value of “absent” pattern in contrast-enhanced ultrasound (CEUS) for the differentiation of solid thyroid nodules, also, to analyze corresponding characteristics of B-scan ultrasound (US) and real-time elastography (RTE). METHODS: A total of 96 patients enrolled in our study underwent conventional US, RTE and CEUS before fine needle aspiration (FNA) or surgery. Thyroid nodules with the same “absent” pattern of contrast-enhancement were evaluated on the basis of different ultrasound features in B-scan US and RTE. Then accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis …of thyroid cancer were investigated respectively. RESULTS: Among the five B-scan US features, nodular border obscurity was most predictive of malignancy (accuracy 84.4%, sensitivity 75.0%, specificity 84.8%, p  < 0.05). Nevertheless, none of other ultrasound features including RTE was significantly different between benign and malignant thyroid nodules (p  > 0.05). Besides, both echohomogeneity and RTE had a high sensitivity of 100%. CONCLUSIONS: Combined with medical history, our study allows to identify a specific role for “absent” pattern of CEUS in the differentiation of thyroid nodules with suspicious ultrasound features in conventional B-scan US and RTE. Show more

Keywords: Thyroid nodules, contrast-enhanced ultrasound, B-scan US, real-time elastography, fine-needle aspiration

DOI: 10.3233/CH-152020

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 325-334, 2016

Authors: Chen, Qingsong | Lang, Li | Xiao, Bin | Lin, Hansheng | Yang, Aichu | Li, Hongling | Tang, Shichuan | Huang, Hanlin

Article Type: Research Article

Abstract: OBJECTIVE: To explore whether polymorphic variants of the HTR1B gene are associated with the susceptibility of Raynauds’ Phenomenon (RP) coursed by vibration. METHODS: 148 subjects exposed to vibration for more than 2 years were classified into either induced white finger (VWF) group (n  = 72), or non-VWF group (n  = 76). Vibration exposure levels were measured and assessed following ISO 5349-1:2001 protocol. All workers were genotyped by sequencing for the single nucleotide polymorphisms (SNPs) in the 5′ -flanking and coding region of HTR1B . Genetic characteristics and linkage disequilibrium (LD) were analyzed with Haploview. Serum serotonin levels of …each subject were detected using ELISA. The association between the susceptibility of vascular damage and genotype was analyzed via logistic regression. RESULTS: 7 known SNPs were obtained and their allele frequencies were inserted into the Hardy-Weinberg equilibrium. rs6297 variant genotype had an increased risk of VWF compared with wild genotype (OR = 2.14, 95% CI = 1.04– 4.58, P  < 0.05). rs6298 mutant type (AG+GG) was found to have a significant interaction on vibration exposure LN(CEI), accounting for VWF occurrence. LN(5-HT) level is significantly different between the VWF group (x ¯ ± s = 1.99±1.09 ng/mL) and the non-VWF group (x ¯ ± s = 2.72±1.47 ng/mL). CONCLUSIONS: Serotonin levels may affect the progression of secondary RP. Polymorphic variants of the HTR1B gene are associated with the susceptibility of secondary RP in vibration-exposed occupational populations of Chinese Han people. Show more

Keywords: Raynauds’ Phenomenon (RP), HTR1B, single nucleotide polymorphisms, vascular damage, vibration-induced white finger (VWF)

DOI: 10.3233/CH-152021

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 335-347, 2016

Authors: Sloop, Gregory D. | Bialczak, Jessica K. | Weidman, Joseph J. | St. Cyr, J.A.

Article Type: Research Article

Abstract: Uric acid may be a risk factor for atherosclerotic cardiovascular disease, although the data conflict and the mechanism by which it may cause cardiovascular disease is uncertain. This study was performed to test the hypothesis that uric acid, an anion at physiologic pH, can cause erythrocyte aggregation, which itself is associated with cardiovascular disease. Normal erythrocytes and erythrocytes with a positive direct antiglobulin test for surface IgG were incubated for 15 minutes in 14.8 mg/dL uric acid. Erythrocytes without added uric acid were used as controls. Erythrocytes were then examined microscopically for aggregation. Aggregates of up to 30 erythrocytes were noted …when normal erythrocytes were incubated in uric acid. Larger aggregates were noted when erythrocytes with surface IgG were incubated in uric acid. Aggregation was negligible in controls. These data show that uric acid causes erythrocyte aggregation. The most likely mechanism is decreased erythrocyte zeta potential. Erythrocyte aggregates will increase blood viscosity at low shear rates and increase the risk of atherothrombosis. In this manner, hyperuricemia and decreased zeta potential may be risk factors for atherosclerotic cardiovascular disease. Show more

Keywords: Atherosclerotic cardiovascular disease, uric acid, erythrocyte aggregation, zeta potential, risk factor

DOI: 10.3233/CH-152023

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 349-359, 2016

Authors: Xue, Li-Yun | Lu, Qing | Huang, Bei-Jian | Li, Cui-Xian | Yan, Li-Xia | Wang, Wen-Ping

Article Type: Research Article

Abstract: We aimed to assess the difference of enhancement patterns among the three RCC subtypes with contrast-enhanced ultrasound (CEUS). Two hundreds cases of pathologically proved clear cell renal cell carcinomas (ccRCC), 58 papillary renal cell carcinomas (pRCC) and 51 chromophobe renal cell carcinomas (chRCC) underwent preoperative conventional ultrasound and CEUS. The wash-in and wash-out pattern, peak enhancement degree and homogeneity, and the presence of pseudocapsule were evaluated by two blinded observers respectively. The interreader agreement in the characterization of CEUS features between two observers was good (κ  = 0.649–0.775). Compared with pRCCs and chRCCs, ccRCCs demonstrated higher frequency of simultaneous wash-in …pattern, hyperenhancement and heterogeneity with necrotic areas. Most pRCCs and chRCCs manifested hypoenhancement, homogeneity, fast wash-out and presence of pseudocapsule. The only difference we obtained between pRCC and chRCC was the wash-in pattern, with slow wash-in in pRCC and simultaneous wash-in in chRCC. In small lesions with long diameter≤3 cm, the majority of the three subtypes of RCC showed homogeneous enhancement and there was no difference among them. CEUS was a useful method to preoperatively differentiate the ccRCC from non-ccRCC subtypes. There were no distinguishing features identifid on CEUS that allowed reliable differentiation of pRCC from chRCC. Show more

Keywords: Clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma, contrast-enhanced ultrasonography, differential diagnosis

DOI: 10.3233/CH-152024

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 361-371, 2016

Authors: Thummala, A.S. | Leach, J.K. | Patterson, E. | O’Rear, E.A.

Article Type: Research Article

Abstract: BACKGROUND AND PURPOSE: It is known that encapsulation can alter the delivery of plasminogen activators by flow to accelerate fibrinolysis while other experimental studies suggest encapsulation may reduce the risk of hemorrhage with administration of the agent. The aim of this research is to resolve the effect of encapsulation on fibrinolysis and bleeding in the microcirculation. METHODS: An established rabbit model of fibrinolytic hemorrhage was utilized to explore the potential of encapsulation to limit bleeding. Equal dosages of free or microencapsulated streptokinase (MESK) were infused to initiate thrombolysis of small vessel clots while tracking blood loss. …RESULTS: Compared to free streptokinase, significant improvements in bleeding were observed with MESK as demonstrated by (1) delayed onset of bleeding, (2) shortened duration, and (3) reduction in the volume of lost blood, consistent with less systemic fibrinogen degradation. CONCLUSIONS: Findings demonstrate that encapsulation of streptokinase can inhibit clot lysis in small vessels. Combined with prior work on accelerated thrombolysis, results suggest a time-based regimen for avoiding bleeding complications during thrombolytic therapy with encapsulated agent. Show more

Keywords: Drug delivery, thrombolysis, transport, plasminogen activator, fibrinolysis

DOI: 10.3233/CH-152030

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 373-379, 2016

Authors: Nemeth, Norbert | Sogor, Viktoria | Kiss, Ferenc | Ulker, Pinar

Article Type: Research Article

Abstract: We hypothesized that the results of red blood cell mechanical stability test show interspecies differences. The comparative investigations were performed on blood samples obtained from rats, beagle dogs, pigs and healthy volunteers. Mechanical stress was applied in nine combinations: 30, 60 or 100 Pa shear stress for 100, 200 or 300 seconds. Generally, rat erythrocytes showed the highest capability of resistance. With the applied combinations of mechanical stress pig erythrocytes were the most sensitive. On human erythrocytes 60 Pa for 200 s was the minimum combination to result significant deformability deterioration. By increasing the magnitude and duration of the applied mechanical stress we …experienced escalating deformability impairment in all species. 100 Pa shear stress for 300 seconds on human erythrocytes showed the largest deformability impairment. The mechanical stability test results were also dependent on osmolality. At hypoosmolar range (200 mOsmol/kg) the mechanical stress improved EI data mostly in rat and porcine blood. At higher osmolality (500 mOsmol/kg), the test did not show detectable difference, while in 250–300 mOsmol/kg range the differences were well observable. In summary, erythrocytes’ capability of resistance against mechanical stress shows interspecies differences depending on the magnitude and duration of the applied stress, and on the osmolality. Show more

Keywords: Red blood cell deformability, mechanical stability, membrane stability, comparative hemorheology, osmotic gradient ektacytometry

DOI: 10.3233/CH-152031

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 381-398, 2016

Authors: Liu, Cuiying | Li, Xiang | Feng, Jiantao | Liao, Fulong | Li, Dongguo | Han, Dong

Article Type: Research Article

Abstract: Identifying effective targets induced by ECM stiffness is of critical importance for treating metastatic cancer diseases, which are followed by changes in the mechanical microenvironment in cancer cells. In this study, polyacrylamide hydrogel substrates with different stiffnesses were prepared and mRNA microarrays were performed to analyze the mRNA expression profiles in breast cancer cell line SK-BR-3 grown on different stiffness substrates. The results indicated that the expressions of 1831 genes were changed significantly in the SK-BR-3 cells on the different stiffness substrates. GO and KEGG pathway analyses of the differently expressed genes in five significant profiles annotated that the most …significant pathways were cell cycle, ubiquitin mediated proteolysis RNA transport and pathways in cancer. Finally, the network of genes and gene interaction based on these differently expressed genes was established, and the phosphorylation of AKT and ERK, respectively the downstreams of the PI3K and Ras signal pathways, was further validated. The genes identified in this study may represent good therapeutic targets, and further study of these targets may help to increase our understanding of the mechanisms underlying the pathological processes and therapy for metastatic breast cancer disease. Show more

Keywords: Stiffness, breast cancer, tumor microenvironment, mRNA microarray, bioinformatics

DOI: 10.3233/CH-162047

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 399-410, 2016

Authors: Li, Hongyi | Yang, Chongqing | Lu, Kuiyuan | Zhang, Liyang | Yang, Jiefu | Wang, Fang | Liu, Dongge | Cui, Di | Sun, Mingjun | Pang, Jianxin | Dai, Luru | Han, Dong | Liao, Fulong

Article Type: Research Article

Abstract: OBJECTIVES: Although the microcirculatory dysfunctions of edema formation are well documented, the draining pattern of dermal edema lacks information. This study was to assess the potential drainage pathways of the interstitial fluid in patients with ankle edema using the anatomical and histological methods. METHODS AND RESULTS: Four amputees of lower leg participated in this study. Fluorescent imaging agent was injected into lateral ankle dermis in one volunteered patient before the amputation and three lower legs after the amputation. Physiologically in the volunteer or enhanced by cyclical compression on three amputated limbs, several fluorescent longitudinal pathways from ankle …dermis to the broken end of the amputated legs were subsequently visualized and studied using histological methods, laser confocal microscopy and electron microscopy methods respectively. Interestingly, the fluorescent pathways confirmed to be fibrous connective tissues and the presence of two types: those of the cutaneous pathway (located in dermis or the interlobular septum among adipose tissues within the hypodermis) and those of the perivascular pathway (located in connective tissues surrounding the veins and the arteries). The intrinsic three-dimensional architecture of each fluorescent pathway was the longitudinally running and interconnected fibril bundles, upon which, an interfacial transport pathway within connective tissues was visualized by fluorescein. CONCLUSIONS: The current anatomical data suggested that a unique long-distance transport pathway composed of oriented fibrous connective tissues might play a pathophysiological role in draining dermal edema besides vascular circulations and provide novel understandings of general fibrous connective tissues in life science. Show more

Keywords: Connective tissues, vascular circulations, interstitial fluid

DOI: 10.3233/CH-162057

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 4, pp. 411-421, 2016