Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Skinner, Sarah | Nader, Elie | Stauffer, Emeric | Robert, Mélanie | Boisson, Camille | Cibiel, Agnès | Foschia, Clément | Feasson, Léonard | Robach, Paul | Millet, Guillaume Y | Connes, Philippe

Article Type: Research Article

Abstract: BACKGROUND: Endurance running events are known to cause inflammation and result in increased cytokine production. However, the effects of ultramarathons on cytokine profiles are not well characterized. OBJECTIVE: The aim of this study was to describe and compare the effects of a trail (40 km) race and an ultra-trail (171 km) race on leukocyte concentrations and cytokine profiles. METHODS: The study was conducted during the Ultra-Trail du Mont Blanc® ultra-marathon running event, and included 11 runners who completed the 40 km trail run and 12 runners who completed the 171 km ultra-trail. Blood samples were taken before and after the …races. RESULTS: Leukocyte concentrations significantly increased after both races. Circulating levels of IL-6, IL-1β, MCP-1, and IFN-γ were significantly higher after the longer race compared to the shorter race. Furthermore, while both races resulted in significant increases in IL-6 and IL-8, only the longer race resulted in significant increases in MIP-1β, IL-7, IL-17a, and IL-4. CONCLUSIONS: These results illustrate that a 171 km ultra-trail race results in greater modulations in cytokine profiles than a traditional trail race. Show more

Keywords: Running, exercise, ultra-trail, inflammation, cytokines profile, leukocytes

DOI: 10.3233/CH-211121

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-10, 2021

Authors: Caimi, Gregorio | Hopps, Eugenia | Montana, Maria | Urso, Caterina | Carollo, Caterina | Canino, Baldassare | Lo Presti, Rosalia

Article Type: Research Article

Abstract: The goal of this research was to evaluate the plasma concentration of MMP-9 and its tissue inhibitor (TIMP-1) in different clinical conditions. It included several groups of subjects: 31 overweight subjects; 91 obese adults divided into two subgroups according to the BMI value (BMI 30–35 Kg/m2 and BMI >  35 Kg/m2 ); 90 subjects with metabolic syndrome (MS) divided into two subgroups (with and without diabetes mellitus); 100 subjects with preclinical carotid atherosclerosis (PCA) divided according to the number of cardiovascular risk factors and to the insulin resistance degree; 48 subjects with obstructive sleep apnoea syndrome (OSAS) divided according to the apnoea/hypopnea index …(AHI); 27 subjects with chronic kidney disease (CKD) on conservative management; 31 subjects with CKD on regular haemodialysis treatment. We have found a significant increase of MMP-9 and TIMP-1 in overweight subjects, in obese adult and in MS subjects. In obese adults, the behaviour of these two parameters was not influenced by the degree of obesity, while in the group of MS subjects both these parameters were clearly influenced by the presence of diabetes mellitus. In subjects with PCA, we observed an increase of MMP-9 associated with a significant decrease of TIMP-1; the same trend was found by subdividing the entire group in accordance with the number of cardiovascular risk factors and with the insulin resistance degree. In subjects with OSAS, we noted an increase in MMP-9 and TIMP-1; this increase was more evident in subjects with OSAS having AHI >  30. In individuals with CKD on conservative and haemodialysis treatment we have found, at baseline, a marked increase in MMP-9 and a significant decrease of TIMP-1. In dialyzed subjects, after a standard dialysis session was noted, a significant increase in MMP-9 was associated with a further decrease in TIMP-1. Show more

Keywords: MMP-9, TIMP-1, obesity, metabolic syndrome, preclinical carotid atherosclerosis, OSAS, CKD

DOI: 10.3233/CH-201094

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-16, 2021

Authors: Natrus, Larysa | Ryzhko, Irina | Blazquez-Navarro, Arturo | Panova, Tatyana | Zaychenko, Ganna | Klymenko, Olena | Babel, Nina | Bondur, Vitalii

Article Type: Research Article

Abstract: AIM: The aim of this study was to correlate the content of cells with regulatory molecules associated with angiogenesis in wound healing in a rat model of hyperglycemia. We hypothesize that blood neutrophils are the main VEGF source and can stimulate FLT-1 receptor expression, which is the perquisite for efficient neoangiogenesis. MATERIALS AND METHODS: Kinetic studies of the healing dynamics (3, 7, 14, 21 days) of burn wounds on the skin were conducted in white adult male rats. The content of nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), its receptor (Flt-1) in the regenerated tissue …was analyzed by western blot. Numbers of cells associated with the regenerative process and from peripheral blood (PB) were determined. Additionally a bone marrow (BM) myelogram was conducted. RESULTS: The relative number of peripheral blood (PB) neutrophils was found to be associated with the level of VEGF (R  = 0.708) and Flt-1 (R  = 0.472). The relative number of fibroblasts was also associated with VEGF (R  = 0.562), but not with Flt-1. A negative association was found between the number of neutrophils in the regenerated tissue with VEGF (R  = –0.454) and FLT-1 (R  = –0.665). This confirms our hypothesis, that blood neutrophils are the main VEGF producer that stimulate the expression of the FLT-1 receptor subsequently inducing neoangiogenesis. Furthermore, that under hyperglycemic conditions fibroblasts were highly associated with VEGF (R  = 0.800), while negatively associated with FLT-1 (R  = –0.506). There was a high association between PB neutrophils and newly generated tissue cells: neutrophils (R  = 0.717) and macrophages (R  = 0.622), as well as the association between neutrophils and macrophages (R  = 0.798). This is an indication of chronic inflammation and increased transmigration of blood cells to the burned tissue. CONCLUSION: Blood neutrophils are the main producer of VEGF and stimulate the expression of the FLT-1 receptor. In the context of hyperglycemia the imbalance of receptor and ligand associated with angiogenesis indicates for chronic inflammation: VEGF and FLT-1, which facilitates hypoxia, prevents the physiological course of burn wound healing and may be important factors in impaired tissue regeneration in diabetes. Show more

Keywords: Angiogenesis, granulocytes, neutrophils, macrophages, connective tissue, burn wound

DOI: 10.3233/CH-201077

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2021

Authors: Schmidt, Jeremias | Kruppa, Philipp | Georgiou, Iakovos | Ghods, Mojtaba

Article Type: Research Article

Abstract: BACKGROUND: When performing large volume liposuction, perioperative management of lipedema patients with coagulation disorders remains challenging due to a lack of clinical experience. With a prevalence of 1% of von Willebrand disease (VWD) in the general population, basic knowledge on diagnostic and adapted surgical strategies are essential for patients’ safety. OBJECTIVE: Based on a selective literature review, the purpose of this article is to present a standardized algorithm for diagnosis and perioperative treatment of VWD patients undergoing large volume liposuction. METHODS: The databases MEDLINE (via PubMed) and Web of Science were selectively searched with the term …“(((liposuction) OR (surgery)) OR (lipectomy)) AND (((VWD) OR (hemostaseology)) OR (von Willebrand disease))”. Included were articles published in English or German until November 2020. RESULTS: The evidence for large volume liposuctions in patients with VWD is limited. Experience is largely based on operations with similar bleeding risks. A safe performance requires an adjustment of the surgical technique and a customized perioperative drug substitution plan. According to the current literature, perioperative thromboembolic events appear to be rare with adequate drug treatment. CONCLUSION: The implementation of the developed diagnostic and treatment algorithm may help further reducing bleeding complications and improve the safety for treated patients. Show more

Keywords: Lipedema, liposuction, von Willebrand disease, hemostaseology

DOI: 10.3233/CH-201063

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2021

Authors: Evans, V.J. | Lawrence, M. | Whitley, J. | Johns, C. | Pillai, S. | Hawkins, K. | Power, K. | Morris, K. | Williams, R. | Evans, P.A.

Article Type: Research Article

Abstract: BACKGROUND: The acute vascular disease deep vein thrombosis (DVT) requires oral anticoagulants to prevent progression. Monitoring therapeutic efficacy of direct oral anticoagulants (DOAC), including rivaroxaban, is problematic as no reliable test is available. Advances in rheometry have led to the development of a functional coagulation biomarker using Gel Point (GP) analysis which assesses clot structure formation. The biomarker measures incipient clot formation time (TGP ) and quantifies fibrin clot structure in terms of fractal dimension (df ). OBJECTIVE: This study aimed to investigate clot structure formation in first time DVT and the effect of rivaroxaban treatment. …METHODS: This prospective observational cohort study measured the GP and standard laboratory markers at three sample points: pre-treatment and at 20 and 60 days following 15 mg BD and 20 mg OD rivaroxaban respectively. RESULTS: Forty DVT patients (mean age 64 years [SD±14.8]; 23 males, 17 female) were recruited. The results show that DVT vs non-DVT patients did not have a significantly different GP profile (df : 1.72±0.06 vs 1.70±0.06 and TGP : 267±68 sec vs 262±73 sec) with both within the defined healthy index. In addition, rivaroxaban therapy increased TGP to 392 s (±135 s) after 20 days, and subsequently increased to 395 s (±194 s) at 60 days but did not significantly increase df (from 1.69±0.05 to 1.71±0.06). CONCLUSIONS: The results indicate in this cohort of DVT patients there was no underlying hypercoagulable effect as determined by gel point analysis. Furthermore, the anticoagulant effect of rivaroxaban prolonged clotting, suggesting a protective effect against clot formation, without significantly reducing clot microstructural properties. Show more

Keywords: Rivaroxaban, coagulation inhibitors, venous thrombosis, clot structure, biomarkers

DOI: 10.3233/CH-201030

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Cao, Jiaying | Dong, Yi | Fan, Peili | Mao, Feng | Chen, Kailing | Chen, Rongxin | Huang, Beijian | Cheng, Yaqing | Wang, Wen-Ping

Article Type: Research Article

Abstract: BACKGROUND: Dynamic three-dimensional contrast-enhanced ultrasound (3D-CEUS) with quantitative analysis is available in recent years. It can reduce the quantitative sampling error caused by the inconsistency of different sections in order to evaluate local treatment response of hepatocellular carcinoma (HCC) accurately. OBJECTIVE: To investigate the value of dynamic 3D-CEUS in evaluating the early response to transarterial chemoembolization (TACE) treatment in patients with advanced HCC lesions. METHODS: In this prospective study, both two-dimensional (2D) CEUS and dynamic 3D-CEUS were performed on 40 HCC patients who scheduled for TACE at baseline (T0) and 1–3 days (T1) after treatment. Tumor …microvascular perfusion changes were assessed by CEUS time-intensity curve (TIC) and quantitative parameters. According to contrast-enhanced computed tomography (CT) and magnetic resonance (MR) imaging 1 month after treatment results, patients were divided into responders and non-responders groups. The changes of perfusion parameters of both 2D-CEUS and 3D-CEUS were compared between responders and non-responders groups before and after TACE treatment. RESULTS: Before and after TACE treatment, no significant difference in maximum diameter of HCC lesions between the two groups could be found. There were more significant differences and ratios of perfusion parameters in 3D-CEUS quantitative analysis than in 2D-CEUS. The mutual significant differences and ratios of 2D-CEUS and 3D-CEUS included peak intensity (PI) difference, PI ratio, ratio of area under the curve (A), ratio of area under the wash-out part (AWO) and slope (S) difference. The former 4 corresponding parameters were better on 3D-CEUS than on 2D-CEUS. CONCLUSION: Dynamic 3D-CEUS can be used as a potential imaging method to evaluate early treatment response to TACE in advanced HCC patients. Show more

Keywords: Contrast-enhanced ultrasound, advanced, hepatocellular carcinoma, three-dimensional, treatment response

DOI: 10.3233/CH-201086

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2021

Authors: Zhao, Shanjun | Yu, Lei

Article Type: Research Article

Abstract: BACKGROUND: Ischemia reperfusion usually results in certain degree of damage to the myocardium, which is called myocardial ischemia/reperfusion (I/R) injury. OBJECTIVE: Previous studies have found that Sirt1 plays a critical role in I/R injury by protecting cardiac function. SRT1460 is the activator for Sirt1 that participates in the regulation of various diseases. However, whether SRT1460 has any effects on myocardial I/R injury needs further study. METHODS: The I/R rat model and H/R H9C2 model were established to simulate myocardial I/R injury. The infarct area of the rat heart was examined through TTC staining. The EF and …FS of rats were detected through echocardiography. The levels of CK-MB, LDH, MDA, SOD and CK in cardiac tissues, serum or H9C2 cells were measured using commercial kits. Cell viability was assessed through MTT assay. Apoptosis was determined through flow cytometry analysis. Sirt1 expression was measured through western blot. RESULTS: Our work found that SRT1460 reduced the infarct area of the heart induced by myocardial I/R injury. In addition, SRT1460 was confirmed to ameliorate cardiac dysfunction induced by myocardial I/R injury. Further exploration discovered that SRT1460 weakened oxidative stress induced by myocardial I/R injury. Findings from in vitro assays demonstrated that SRT1460 relieved injury of H/R-treated H9C2 cells. Finally, rescue assays proved that Sirt1 knockdown reversed the protective effects of SRT1460 on the injury of H/R-treated H9C2 cells. CONCLUSION: Sirt1 activated by SRT1460 protected against myocardial I/R injury. This discovery may offer new sights on the treatment of myocardial I/R injury. Show more

Keywords: Sirt1, SRT1460, myocardial I/R injury

DOI: 10.3233/CH-201061

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Glazkova, P.A. | Kulikov, D.A. | Glazkov, A.A. | Terpigorev, S.A. | Rogatkin, D.A. | Shekhyan, G.G. | Krasulina, K.A. | Kulikov, A.V. | Makmatov-Rys, M.B. | Paleev, F.N.

Article Type: Research Article

Abstract: BACKGROUND: The role of microcirculatory disorders is progressively being accepted in the pathogenesis of cardiovascular diseases. OBJECTIVE: The purpose of current study is to assess whether we can consider skin microcirculation disorders as a biomarker of cardiovascular events. METHODS: Group 1 consisted of healthy volunteers (n  = 31); group 2 (n  = 42) consisted of patients with diseases that increase the risk of cardiovascular events; group 3 (n  = 39) included patients with the history of cardiovascular events. Skin microcirculation measurement was performed using laser Doppler flowmetry during the heating test. RESULTS: LDF parameters reflecting the rapid …response of microcirculation to heating (“Slope 120 s” and “Slope 180 s”) significantly differed in three groups (p  < 0.05). A decrease in the “Slope 180 s” parameter less than 0.5 PU/s is associated with cardiovascular events (sensitivity 69.2%, specificity 66.7%; the area under the ROC curve, 0.667; 95% confidence interval [CI], 0.545–0.788, p  = 0.01). Multivariable logistic regression analysis revealed that “Slope 180 s≤0.5 PU/s” was significantly related to cardiovascular events (adjusted odds ratio = 3.9, p  = 0.019, CI 95% 1.2–12). CONCLUSIONS: Reduced reactivity of the skin microcirculation may be useful as a biomarker of severe damage to the cardiovascular system and is promising as a risk factor for cardiovascular events. Show more

Keywords: Cardiovascular diseases, skin, microcirculation, laser-Doppler flowmetry, risk factors, diabetes mellitus, hypertension

DOI: 10.3233/CH-201016

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Maxeiner, Andreas | Fischer, Thomas | Stephan, Carsten | Treskatsch, Selda | Baur, Alexander Daniel Jacques | Jung, Ernst-Michael | Hamm, Bernd | Lerchbaumer, Markus Herbert

Article Type: Research Article

Abstract: BACKGROUND: Tissue Doppler imaging (TDI) uses the Doppler principle to quantify the movement of biological tissues. OBJECTIVE: To investigate the contribution of TDI parameters derived during magnetic resonance imaging and ultrasound (MRI/US) fusion-guided biopsy for prostate cancer (PCa) discrimination. METHODS: From March 2016 to Dec. 2018, 75 men with suspected PCa prospectively underwent fusion-guided prostate biopsy. TDI overlaid on predefined target lesion were compared to the confirmed contralateral tumor-free area of the prostate gland (using Image J). Diagnostic value of TDI parameters was assessed using histopathology as standard of reference. RESULTS: Thirty-seven patients were …diagnosed with PCa (49.3%), among them 27 with clinically significant PCa (Gleason score >  3 + 3 = 6 (ISUP 1). The LES/REF ratio was lower in confirmed PCa patients compared to patients without PCa (0.42, IQR, 0.22–0.59 vs. 0.52, IQR, 0.40–0.72, p  = 0.017). TDI parameters allowed differentiation of low-risk from high-to-intermediate-risk PCa (ISUP 2 versus ISUP 3) based on lower pixel counts within the target ROI (1340, IQR 596–2430 vs. 2687, IQR 2453–3216, p  = 0.004), lower pixel percentage (16.4 IQR 11.4–29.5 vs. 27.3, IQR 22.1–39.5; p  = 0.005), and lower LES/REF ratios (0.29, IQR 0.19–0.51 vs. 0.52, IQR 0.47–0.74, p  = 0.001). CONCLUSION: TDI of prostate lesions prelocated by MRI discriminates between cancerous and noncancerous lesions and further seems to enable characterization of PCa aggressiveness. This widely available US technique may improve confidence in target lesion localization for tissue sampling. Show more

DOI: 10.3233/CH-201035

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2021

Authors: Macedo, Lucas Sousa | Rusig, Renato Polese | Silva, Gustavo Bersani | Cho, Alvaro Baik | Hsiang Wei, Teng | Bernardelli Iamaguchi, Raquel

Article Type: Research Article

Abstract: BACKGROUND: Microsurgical flaps are widely used to treat complex traumatic wounds of upper and lower limbs. Few studies have evaluated whether the vascular changes in preoperative computed tomography angiography (CTA) influence the selection of recipient vessel and type of anastomosis and the microsurgical flaps outcomes including complications. OBJECTIVE: The aim of this study was to evaluate if preoperative CTA reduces the occurrence of major complications (revision of the anastomosis, partial or total flap failure, and amputation) of the flaps in upper and lower limb trauma, and to describe and analyze the vascular lesions of the group with CTA …and its relationship with complications. METHODS: A retrospective cohort study was undertaken with all 121 consecutive patients submitted to microsurgical flaps for traumatic lower and upper limb, from 2014 to 2020. Patients were divided into two groups: patients with preoperative CTA (CTA+) and patients not submitted to CTA (CTA–). The presence of postoperative complications was assessed and, within CTA+, we also analyzed the number of patent arteries on CTA and described the arterial lesions. RESULTS: Of the 121 flaps evaluated (84 in the lower limb and 37 in the upper limb), 64 patients underwent preoperative CTA. In the CTA+ group, 56% of patients with free flaps for lower limb had complete occlusion of one artery. CTA+ patients had a higher rate of complications (p  = 0.031), which may represent a selection bias as the most complex limb injuries and may have CTA indicated more frequently. The highest rate of complications was observed in chronic cases (p  = 0.034). There was no statistically significant difference in complications in patients with preoperative vascular injury or the number of patent arteries. CONCLUSIONS: CTA should not be performed routinely, however, CTA may help in surgical planning, especially in complex cases of high-energy and chronic cases, since it provides information on the best recipient artery and the adequate level to perform the microanastomosis, outside the lesion area. Show more

Keywords: Computed tomography angiography, free flap, microvascular free flap, trauma surgery, complex injuries, complication rates

DOI: 10.3233/CH-200986

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2021