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

Authors: Wei, Linlin | Zeng, Kexue | Gai, Juanjuan | Zhou, Feixiong | Wei, Zhenglin | Bao, Qinghui

Article Type: Research Article

Abstract: OBJECTIVE: To study the effect of acupuncture on neurovascular units after cerebral infarction (CI) in rats through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. METHODS: A total of 36 Sprague-Dawley rats were randomly divided into sham group (n  = 12), model group (n  = 12) and acupuncture group (n  = 12). The external carotid artery was only exposed in model group, while the post-CI ischemia-reperfusion model was established using the suture method in the other 2 groups. After modeling, the rats in sham group and model group were fixed and sampled, while those in acupuncture group were treated with …acupuncture intervention for 2 weeks and sampled. The neurological deficits of rats were evaluated using the Zea-Longa score, and the spatial learning and memory of rats were detected via water maze test. Moreover, the expressions of vascular endothelial growth factor (VEGF), growth associated protein-43 (GAP-43) and synuclein (SYN) in brain tissues were detected via immunohistochemistry, and the relative protein expressions of PI3K p85, PI3K p110 and p-AKT were detected via Western blotting. The messenger ribonucleic acid (mRNA) expressions of VEGF, GAP-43 and SYN were detected via quantitative polymerase chain reaction (qPCR). RESULTS: The Zea-Longa score was significantly increased in model group and acupuncture group compared with that in sham group (p  < 0.05), while it significantly declined in acupuncture group compared with that in model group (p  < 0.05). The escape latency was significantly prolonged and the times of crossing platform were significantly reduced in model group and acupuncture group compared with those in sham group (p  < 0.05), while the escape latency was significantly shortened and the times of crossing platform were significantly increased in acupuncture group compared with those in model group (p  < 0.05). The positive expressions of VEGF, GAP-43 and SYN were obviously increased in model group and acupuncture group compared with those in sham group (p  < 0.05), while they were obviously increased in acupuncture group compared with those in model group (p  < 0.05). Besides, model group and acupuncture group had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than sham group (p  < 0.05), while acupuncture group also had significantly higher relative protein expressions of PI3K p85, PI3K p110 and p-AKT than model group (p  < 0.05). The relative mRNA expressions of VEGF, GAP-43 and SYN were remarkably increased in model group and acupuncture group compared with those in sham group (p  < 0.05), while they were remarkably increased in acupuncture group compared with those in model group (p  < 0.05). CONCLUSION: Acupuncture promotes the repair of neurovascular units after CI in rats through activating the PI3K/AKT signaling pathway, thereby exerting a protective effect on neurovascular units. Show more

Keywords: Acupuncture, cerebral infarction, PI3K/AKT signaling pathway, neurovascular units

DOI: 10.3233/CH-190659

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Liu, Ying | Huang, Zhen-Li | Zhang, Zhen | Gong, Lin | Zhang, Shuang-Chuan | Zhou, Yu-Xin

Article Type: Research Article

Abstract: Background: N-terminal pro-B-type natriuretic peptide (NTproBNP) appears to be a useful tool for diagnosing hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. However, a consensus for its application has not been reached. Objective: The present study aims to evaluate the role of NTproBNP in predicting hsPDA in preterm infants, and explore the optimal cutoff value and testing-time. Methods: A prospective blind study of 120 preterm infants with birth weights of < 1,500 g was conducted at the NICU of Peking University Shenzhen Hospital. Blood samples were successively collected on the first three days after birth for NTproBNP analysis. …Echocardiographies were performed on day three of life to confirm the status of the ductus arteriosus. A receiver operating characteristic curve (ROC) analysis was performed to determine the ability of NTproBNP to recognize hsPDA. Results: NTproBNP was significantly higher in infants with hsPDA, than in infants in the control group, on both day two (P  < 0.001) and day three (P  < 0.001). On day two, a NTproBNP cutoff value of 3,689.0 pmol/L offered an optimal predictive value for hsPDA, while on day three, the optimal cut-off value for hsPDA was 2,331.5 pmol/L. The investigators proposes day three of life (48–72 hours) as the optimal testing time. Conclusion: The NTproBNP biomarker during the early neonatal period can be a useful tool for screening and assessing hsPDA in premature infants, especially on day three of life. Show more

Keywords: HsPDA, NTproBNP, Preterm infants, Very low birth weight infants

DOI: 10.3233/CH-190803

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2020

Authors: Pang, Mengru | Lei, Xiaoxuan | Yao, Zexin | Chen, Caihong | Cheng, Biao

Article Type: Research Article

Abstract: It has been reported that the beta-adrenergic receptor blocker (propranolol) and the a-adrenergic receptor (AR) blocker (phentolamine) both can inhibit human endothelial cell (EC) angiogenesis in vitro . However, it is unknown whether this inhibition also acts on pericytes. The present study aimed to determine how pericytes react to treatment with an a-/β- AR blocker. In the study, cell proliferation assays and scratch assay were performed to assess the effect of phentolamine or propranolol on cell proliferation and migration. Western blot and ELISA were employed to determine changes in VEGF-A and Ang-1 expression levels. The results indicated that the nonselective …a-/β- AR blocker inhibited the proliferation, migration, and secretion of pericytes. The use of the nonselective a-/β- AR blocker might have an impact on vascularization and vascular maturation. Our research suggests the rational use of nonselective a-/β- AR blockers to treat angiogenesis-dependent diseases. Show more

Keywords: Adrenergic receptor blocker, phentolamine, propranolol, pericytes, angiogenesis

DOI: 10.3233/CH-190780

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Liu, Xuanwei | Zhao, Na’na | Zeng, Kexue | Xiao, Peng | Sheng, Pengjie | Luo, Xun | Wang, Yulong

Article Type: Research Article

Abstract: OBJECTIVE: This study aims to investigate the effect of nimodipine combined with betahistine on the levels of CRP and other inflammatory cytokines, as well as vascular endothelial function in patients with hypertensive cerebral vasospasm. METHODS: A total of 80 patients with hypertensive cerebral vasospasm from March 2016 to September 2018 were enrolled and randomly equally divided into two groups. At 1 week before enrollment, the application of all antihypertensive drugs was stopped. Then amlodipine tablets were used in control group, based on which nimodipine tablets were applied in observation group. All the patients included were followed up for …1 month. The changes in the cerebral vasospasm index in the course of treatment as well as inflammatory cytokines and indicators related to vascular endothelial function at 1 month after treatment were measured and compared between the two groups. The correlations of the cerebral vasospasm index with the changes in inflammatory cytokines and vascular endothelial function-related factors in the body were analyzed. Finally, the effective rates of blood pressure regulation and cerebral vasospasm treatment were compared, while the adverse reactions and the overall clinical treatment effect of the two groups were evaluated. RESULTS: The cerebral vasospasm indexes in observation group were significantly lower than those in control group at 3 d, 1 week and 1 month after treatment (p  < 0.05). At 1 month after treatment, the levels of inflammatory cytokines such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α ) in observation group were significantly reduced compared to those in control group (p  < 0.05). As for vascular endothelial function-related indicators, the endothelin-1 (ET-1) level in observation group was markedly lower than that in control group, whereas the level of nitric oxide (NO) was statistically higher than that in control group (p  < 0.05). The cerebral vasospasm index was statistically positively correlated with changes in hs-CRP, IL-6, TNF-α and ET-1 (p  < 0.05), but negatively correlated with changes in NO (p  < 0.05). Besides, the effective rates of blood pressure regulation and cerebral vasospasm treatment in observation group were significantly higher than those in control group (p  < 0.05). The overall treatment effective rate in observation group was markedly higher than that in control group (p  < 0.05), and there were no significant differences of adverse reactions between the two groups (p  > 0.05). CONCLUSION: For the treatment of hypertensive cerebral vasospasm, combined application of betahistine on the basis of nimodipine can effectively reduce the body’s aseptic inflammatory responses, improve vascular endothelial function and increase the cerebral circulation blood flow, which offers a favorable strategy for clinical therapy. Show more

Keywords: Key words: Betahistine, hypertension, cerebral vasospasm, inflammatory cytokine, vascular endothelial function, nimodipine

DOI: 10.3233/CH-190589

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Dragic, Sasa | Momcicevic, Danica | Zlojutro, Biljana | Jandric, Milka | Kovacevic, Tijana | Djajić, Vlado | Gajić, Aleksandar | Talić, Goran | Kovacevic, Pedja

Article Type: Research Article

Abstract: Roles of nitric oxide (NO) and endothelin-1 (ET-1) in the local regulation of blood flow under physiological conditions are important and well known, while data on their effects and interactions in conditions of hyperbaric hyperoxia is still insufficient. This was a prospective observational study which included patients who underwent hyperbaric oxygen therapy (HBOT) in accordance with existing therapeutic protocol for peripherial arterial disease (PAD) during time period of six months, between january and july of 2016. Clinical stage of PAD according to Fontain was taken into account, as well as risk factors, demographic, anthropometric and clinical characteristics of studied patients. …The study included 64 patients with a mean age (±Sd) 60.2±12.7 years, of whom 28 were female. Patients’ NO serum levels in all observed categories before and after HBOT were not signifficantly different, except for stage II PAD (NObefore HBOT 21.9±9.6 vs. NOafter HBOT 26.2±12.1 (p  = 0.04)). On the contrary, in all studied patients ET-1 level increased signifficantly after HBOT (ET-1before HBOT 4.2±11.6 vs. ET-1after 18.3±21.0 (p  < 0.001)). Treatment of PAD using HBOT leads to the predominance of vasoconstrictor effects probably caused by elevation of serum ET-1 concentrations, while other factors such as exposure time to hyperbaric conditions, activation of antioxidant molecules, and the influx of other interfering substances must be considered in interpreting the effects of NO molecules. Show more

Keywords: Peripherial arterial disease, hyperbaric oxygen therapy, endothelin-1, nitric oxide

DOI: 10.3233/CH-190796

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Park, Seong Jun | Yoon, Jung | Seo, Hong Seog | Lim, Chae Seung

Article Type: Research Article

Abstract: BACKGROUND: Platelet function analysis is crucial in assessing the hemostatic status to evaluate congenital and acquired platelet function defects. The Anysis-200 analyzer is a new automated lab-on-a-chip-based platelet function analyzer. OBJECTIVE: We aimed to evaluate a new platelet function analyzing system, the Anysis-200 in comparison to the Platelet Function Analyzer (PFA)-200 in cardiac patients. METHODS: Citrated blood was collected from 174 patients who visited the Department of Cardiology. The Anysis-200 consists of two kits, the microchips with collagen and epinephrine-coated membrane (C/EPI) or adenosine diphosphate-coated membrane (C/ADP). Platelet clogging in the Anysis-200 is measured by the …blood migration distance obtained by a camera, which is compatible with the closure time in the PFA-200. We performed Anysis-200 and PFA-200 analyzers simultaneously and compared the results. RESULTS: The sensitivity and specificity of the Anysis-200 C/EPI kit in comparison to the PFA-200 C/EPI kit were 63.41% and 91.43%, respectively. Regarding the C/ADP kit, the sensitivity and specificity of the Anysis-200 were 58.97% and 74.29%, respectively. The agreement rate between the Anysis-200 and PFA-200 for C/EPI was 83.35% and 70.14% for C/ADP. CONCLUSIONS: The Anysis-200, which applies a novel method to detect platelet clogging, has shown moderate to fair agreement with the PFA-200. This test is potentially useful for screening cardiac patients with an abnormal platelet function. Show more

Keywords: Platelet function, Anysis-200 analyzer, PFA-200 analyzer

DOI: 10.3233/CH-190801

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Liu, Xiaojun | Wang, Gang | Zhang, Tao

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the changes in the levels of plasm interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α ), C-reactive protein (CRP), matrix metalloproteinase-9 (MMP-9) and endotoxins in patients with acute aortic dissection (AAD). METHODS: 55 AAD patients who were admitted and scheduled to undergo emergency surgery in our hospital from January 2017 to July 2017 were selected and retrospectively analyzed. They were divided into the survival group (n  = 40) and the death group (n  = 15). The levels of plasma IL-6, TNF-α , CRP, MMP-9 and endotoxins at admission and at 6 h, 12 h and 24 h after admission (T0, T1, T2 …and T3) were measured, and the correlations of inflammatory cytokines with endotoxins were analyzed. RESULTS: At T1, T2 and T3, the levels of inflammatory cytokines and endotoxins were increased. The levels of plasma IL-6, TNF-α , CRP, MMP-9 and endotoxins in the death group were significantly higher than those in the survival group at each time point (p  < 0.05 in all comparisons). Neutrophil and platelet counts in the death group were higher than those in the survival group (p  < 0.05). Correlation analyses indicated that the levels of IL-6, TNF-α , CRP and MMP-9 were positively correlated with the level of endotoxin. CONCLUSION: Patients with AAD are often accompanied by systemic inflammatory responses, with inflammation-related cytokines (IL-6, TNF-α , CRP and MMP-9) and endotoxins levels significantly elevated. Combined monitoring of dynamic changes in inflammatory cytokines and endotoxins, as well as early interventions, has important clinical implications for evaluating the prognosis of AAD and reducing mortality. Show more

Keywords: Acute aortic dissection, IL-6, TNF-α, CRP, MMP-9

DOI: 10.3233/CH-190674

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Carlisi, Melania | Mancuso, Salvatrice | Caimi, Gregorio | Siragusa, Sergio

Article Type: Research Article

Abstract: The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and …non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients. Show more

Keywords: Paroxysmal nocturnal hemoglobinuria, complement system, CD55, CD59, thromboembolic risk

DOI: 10.3233/CH-190735

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-13, 2020

Authors: Lerchbaumer, Markus Herbert | Putz, Franz Josef | Rübenthaler, Johannes | Rogasch, Julian | Jung, Ernst-Michael | Clevert, Dirk-Andre | Hamm, Bernd | Makowski, Marcus | Fischer, Thomas

Article Type: Research Article

Abstract: PURPOSE: Contrast-enhanced-ultrasound (CEUS) has been frequently used in assessment of cystic renal lesions. OBJECTIVE: The aim of this study was to investigate the Bosniak classification in CEUS compared to CT and MRI in a multi-center setting. METHODS: Bosniak classification in CEUS examinations of cystic renal lesions were compared to imaging findings in computed-tomography (ceCT) and magnetic-resonance-imaging (ceMRI). Imaging results were correlated to histopathological reports. All examinations were performed by experts (EFSUMB level 3) using up-to-date CEUS examination-protocols. RESULTS: Overall, 173 cystic renal lesions were compared to subgroups CT (n  = 87) and MRI (n  = 86). …Using Bosniak-classification 64/87 renal cysts (73.6%) were rated equal compared to CT with upgrade of four lesions (4.6%) and downgrade of 19 lesions (21.8%) by CT (Intra-class-correlation [ICC] coefficient of 0.824 [p  < 0.001]). CEUS compared to MRI, presenting different scoring especially in classes Bosniak IIF (n  = 16/31) and Bosniak III (n  = 16/28) with an ICC coefficient of 0.651 (p  < 0.001). CONCLUSION: CEUS can visualize even finest septal and small nodular wall enhancement, which may result in an upgrade of cystic lesions into a higher Bosniak class compared to CT or MRI. Thus, a modification of the Bosniak classification on CEUS may reduce unnecessary biopsies and surgery. Show more

Keywords: Contrast-enhanced ultrasound, CEUS, Bosniak, renal cyst

DOI: 10.3233/CH-190764

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Huang, Yunqian | Liu, Qi | Xu, Junmei | Zhu, Wenqian | Jiang, Jianwei | Tang, Lei | Chen, Man

Article Type: Research Article

Abstract: BACKGROUND: Early identification of vulnerable plaques at risk of rupture could help prevent cerebral ischemic stroke in patients with carotid artery disease. OBJECTIVE: To investigate the correlation between contrast-enhanced ultrasound (CEUS) perfusion patterns and serum lipid signatures of carotid artery plaques with the degree of carotid stenosis. METHODS: A total of 80 patients with carotid artery plaques who underwent CEUS were included. All patients underwent CEUS, computed tomography angiography or digital subtraction angiography, and serum lipid testing. RESULTS: The contrast agent enhancement levels and the CEUS perfusion patterns in the plaques were associated with …the degree of carotid stenosis (P  < 0.05). Serum free fatty acid (FFA) was associated with the contrast agent enhancement levels (P  < 0.05), but did not correlate with the degree of stenosis (P  > 0.05). There was no significant difference in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides with respect to contrast agent enhancement levels (P  > 0.05) or the degree of stenosis (P  > 0.05). CONCLUSION: A high level of CEUS perfusion and increased serum FFA levels are indicative of vulnerable carotid plaques, which may be useful for the prediction of stroke in patients with carotid artery disease. Show more

Keywords: Carotid plaque, contrast-enhanced ultrasound perfusion patterns, stenosis, free fatty acid, stroke

DOI: 10.3233/CH-190804

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020