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Objective: This study aimed to analyze the therapeutic effect of Ginkgo biloba extract (EGb 761) on sudden sensorineural hearing loss (SSNHL) and its influence on hemorheology., Methods: The clinical data of patients diagnosed with SSNHL and admitted to the Wendeng Hospital of Traditional Chinese Orthopedics and Traumatology of Shandong Province from May 2020 to May 2023 were retrospectively analyzed. Based on different clinical treatment protocols, patients were divided into a control group (treated with routine treatment) and an administration group (treated with routine treatment + EGb 761). Both groups underwent drug treatment for 10 days. Subsequently, the hearing threshold, hemorheological parameters (blood high shear viscosity, blood low shear viscosity, plasma viscosity, and platelet aggregation rate) and inflammatory factors and serum levels (C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble vascular cell adhesion molecule-1) of these groups were compared., Results: This study comprised 120 patients, with 66 cases in the control group and 54 cases in the administration group. Following treatment, the total effective rate of the administration group was significantly higher than that of the control group (90.74% vs. 72.73%) (P-value < 0.05). The hearing threshold, hemorheological parameters, inflammatory factors, and serum levels were significantly lower in the administration group than in the control group (P-value < 0.05)., Conclusions: Compared with routine treatment, joint EGb 761 in the SSNHL treatment may improve the hearing threshold and hemorheological indexes of patients, inhibit the inflammatory response, and promote the recovery of hearing function. Moreover, no serious adverse reactions are observed, indicating adequate safety., (Copyright © 2024 Noise & Health.)

Diabetes mellitus (DM) is a complex, chronic metabolic disorder characterized by impaired regulation of blood glucose levels. Zinc (Zn) is an essential trace elements that plays a role in various physiological processes within the body, including those related to diabetes. The current study was investigated the effect of Zn supplementation on hemorheological parameters in a rat model of DM. After induction of DM, 32 male Wistar albino rats were divided into four groups: control, Zn, DM, and Zn+DM. Whole blood viscosity (WBV) was determined by using digital cone and plate viscometer and plasma viscosity (PV) was determined by a Coulter Harkness capillary viscometer. The rats in the DM Group showed a decrease in both Zn levels and body weight, as well as an increase in glucose levels when compared to the control group. Diabetic rats supplemented with Zn displayed lower blood glucose levels and higher concentrations of Zn compared to the DM Group. The higher PV and lower hematocrit level were measured in DM Group than control group and lower PV, higher hematocrit level were measured in Zn+DM group than DM Group. The WBV was measured at four different shear rates (57.6-115.2 - 172.8-230.4 s -1 ). A statistically significant increase was observed in the DM group compared to the control group. Additionally, a statistically significant decrease was observed in the Zn+DM Group compared to the DM Group at a shear rate of 230.4 s -1 . Erythrocyte rigidity index (T k ) and oxygen delivery index (ODI) were computed under conditions of high shear rate. The rats in the DM group exhibited a reduction in ODI and an elevation in T k in comparison to the control group. Conversely, the diabetic rats supplemented with Zn exhibited decreased T k and increased ODI compared to the DM Group. Zn supplementation seems to have a potential beneficial effect for protecting adverse affect of diabetes on hemorheogical parameters and for maintaining vascular health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Devis Ozcelik reports financial support was provided by Istanbul University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To investigate the effect of low-dose aspirin combined with vitamin E on the incidence of intrauterine growth restriction and hemorheological indexes of pregnant women in patients with gestational hypertension., Method: 134 elderly patients with chronic urticaria treated in our hospital from November 2017 to November 2020 were studied. According to the treatment methods, they were randomly divided into observation and control groups. There were 67 patients in the observation group, aged 20-37 years, with an average of (25.7 ± 2.75) years. There were 67 patients in the control group, aged 21-35 years, with an average of (26.3 ± 3.17) years. No significant difference was observed between the two groups ( P > 0.05)., Results: The number of cases with postpartum hemorrhage and intrauterine growth restriction in the observation group was less than that in the control group. The total incidence rate was lower than that in the control group. There were significant differences in the above results ( P < 0.05). The number of patients with preterm birth in the observation group was less than that in the control group, but there was no significant difference in the results ( P > 0.05). The head circumference, abdominal circumference, biparietal diameter, and femoral length diameter in the control and observation groups increased significantly after treatment ( P < 0.05). Compared with the control group, the head circumference, abdominal circumference, biparietal diameter, and femoral diameter in the observation group increased more after treatment, and the results were statistically poor ( P < 0.05). The systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the control and observation groups decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, the systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the observation group decreased more after treatment. The results were statistically different ( P < 0.05). The plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the control and observation groups decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, plasma viscosity levels, whole blood high shear viscosity, and whole blood low shear viscosity in the observation group decreased more after treatment, and the results were statistically different ( P < 0.05). The control and observation groups' fetal systolic/diastolic pressure and pulsatile index decreased significantly after treatment, and the results were statistically different ( P < 0.05). Compared with the control group, the fetal systolic/diastolic blood pressure and pulsatile index in the observation group decreased more after treatment, and the results were statistically poor ( P < 0.05)., Conclusion: Low-dose aspirin combined with vitamin E is effective in treating intrauterine growth restriction in patients with gestational hypertension. It can effectively control the blood pressure and blood flow of patients and newborns and improve pregnancy outcomes without increasing the incidence of adverse reactions. It is worthy of clinical promotion., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Tengfei Shan et al.)

Curcuma wenyujin Y.H. Chen et C. Ling rhizome (also called EZhu in China) has long been used as plant medicine for its traditional effect on promoting blood circulation and remove blood stasis. However, the active components of EZhu are still unclear at present. This research is managed to investigate the pharmacodynamics material basis on removing blood stasis of EZhu by exploring the spectrum-effect relationship between UPLC-Q/TOF-MS fingerprints and pharmacologic actions. Hemorheology and related functional parameters were detected to evaluate the pharmacologic actions of EZhu. Relative content Changes of components in rat plasma were detected by UPLC-Q/TOF-MS. A compound-target-pathway network was built to predict the pharmacological activity of components in plasma. Then, bivariate correlation analysis (BCA) was used to explore the correlation degree between components in plasma and pharmacologic actions of EZhu. In UPLC-Q/TOF-MS fingerprints of rat plasma, 10 prototype components were identified. BCA results show that 8 components were concerned with the pharmacological activity for treating blood stasis syndrome (BSS) in varying degrees (R > 0.5, P < 0.05). Among them, zedoarofuran and curzerenone have shown correlation with more pharmacological indicators. The network predicted that 80 targets were closely related to 10 components, in which 48 targets were connected with 159 metabolic pathways including arachidonic acid metabolism, sphingolipid signaling pathway, and linoleic acid metabolism. Overall, this study provided a scientific basis for TCM quality control to ensure its safety and efficacy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hawthorn, a commonly used traditional Chinese medicine, has been suggested to have therapeutic effects on cardiovascular disease. However, effective fractions of hawthorn extract in the treatment of cardiovascular disease, together with possible therapeutic mechanisms, remain unclear. This study aimed to investigate the effects of four different polar fractions of hawthorn extract on blood stasis model rats, and explore the possible metabolic mechanisms by using a liquid chromatography-mass spectrometry metabolomics approach. Evaluation of hemorheology and fibrinogen showed that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats. Furthermore, metabolomics analysis showed that n-butanol and ethyl acetate fractions of hawthorn extract could reverse imbalanced biomarkers in plasma and urine of blood stasis model rats. Additionally, metabolic pathway analysis revealed that plasma biomarkers were responsible for several important pathways, including d-glutamine and d-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, sphingolipid metabolism, and arginine biosynthesis. Meanwhile, urine biomarkers were responsible for some important pathways, including phenylalanine metabolism, tyrosine metabolism, and lysine degradation. This study demonstrated that n-butanol and ethyl acetate fractions of hawthorn extract had significant therapeutic effects on blood stasis model rats, and the underlying mechanisms involved multiple metabolic pathways., (© 2021 Wiley-VCH GmbH.)

This work presents a semi-quantitative spectroscopic approach, including FTIR-ATR and Raman spectroscopies, for the biochemical analysis of red blood cells (RBCs) supported by the biochemical, morphological and rheological reference techniques. This multi-modal approach provided the description of the RBC alterations at the molecular level in a model of accelerated aging induced by administration of D-galactose (D-gal), in comparison to natural aging. Such an approach allowed to conclude that most age-related biochemical RBC membrane changes (a decrease in lipid unsaturation and the level of phospholipids, or an increase in acyl chain shortening) as well as alterations in the morphological parameters and RBC deformability are well reflected in the D-gal model of accelerated aging. Similarly, as in natural aging, a decrease in LDL level in blood plasma and no changes in the fraction of glucose, creatinine, total cholesterol, HDL, iron, or triglycerides were observed during the course of accelerated aging. Contrary to natural aging, the D-gal model led to an increase in cholesterol esters and the fraction of total esterified lipids in RBC membranes, and evoked significant changes in the secondary structure of the membrane proteins. Moreover, a significant decrease in the phosphorous level of blood plasma was specific for the D-gal model. On the other hand, natural aging induced stronger changes in the secondary structures of the proteins of the RBCs' interior. This work proves that research on the aging mechanism, especially in circulation-related diseases, should employ the D-gal model with caution. Nonetheless, the D-gal model enables to imitate age-related rheological alterations in RBCs, although they are partially derived from different changes observed in the RBC membrane at the molecular level.

Background: Resveratrol (RSV), one of the SIRT1 agonists, has the ability of alleviating severe acute pancreatitis (SAP); however, the concrete protective mechanism remains unknown. It is noteworthy that microcirculation disturbance plays a vital role in SAP, and the SIRT1/FOX1 axis can regulate microcirculation. Therefore, this study is aimed at ascertaining what is the underlying mechanism of the protective effect of RSV on SAP, and whether it is associated with alleviating microcirculation disturbance by regulating the SIRT1/FOX1 axis., Method: The model of SAP was induced by retrograde injection of sodium taurodeoxycholate into the bile duct of the rats. The pancreatic wet/dry weight, ET/NO, and TXB 2 /6-keto-PGF 1 α ratios; microcirculatory function; and SIRT1 activity were examined. ELISA was used to examine the serum level of lipase, amylase, hemorheology, ET, NO, TXB 2 , and 6-keto-PGF 1 α and the content of SIRT1, VEGF, Ang I, and Ang II in the pancreas. RT-PCR was used to examine the mRNA level of VEGF, Ang I, and Ang II. Western blotting was used to detect SIRT1, FOXO1, and acetyl-FOXO1. Immunoprecipitation was used to examine the interaction of SIRT1 and FOXO1., Results: Resveratrol can significantly decrease the expression of lipase, amylase, acetyl-FOXO1, VEGF, Ang II, ET, NO, TXB 2 , and 6-keto-PGF 1 α and the ratio of wet/dry weight, ET/NO, and TXB 2 /6-keto-PGF 1 α by improving microcirculatory dysfunction and blood viscosity in SAP. Moreover, resveratrol can also promote the interaction of SIRT1 and FOXO1 and increase SIRT1 activity and the expression of SIRT1 and Ang I. The SIRT1 inhibitor, Sirtinol (EX527), obliviously reversed the effects of RSV on SAP., Conclusion: Resveratrol can protect rats against SAP, and its protective mechanism is associated with suppressing microcirculation disturbance through activating SIRT1-FOXO1 axis., Competing Interests: The authors declare there is no potential conflict of interest., (Copyright © 2021 Yuping Rong et al.)

Vascular networks consist of hierarchical structures of various diameters and are necessary for efficient blood distribution. Recent advances in vascular tissue engineering and bioprinting have allowed us to construct large vessels, such as arteries, small vessels, such as capillaries and microvessels, and intermediate-scale vessels, such as arterioles, individually. However, little is known about the control of vessel diameters between small vessels and intermediate-scale vessels. Here, we focus on vascular remodeling, which creates lasting structural changes in the vessel wall in response to hemodynamic stimuli, to regulate vessel diameters in vitro. The purpose of this study is to control the vessel diameter at an intermediate scale by inducing outward remodeling of microvessels in vitro. Human umbilical vein endothelial cells and mesenchymal stem cells were cocultured in a microfluidic device to construct microvessels, which were then perfused with a culture medium to induce outward vascular remodeling. We successfully constructed vessels with diameters of 40-150 μm in perfusion culture, whereas vessels with diameters of <20 μm were maintained in static culture. We also revealed that the in vitro vascular remodeling was mediated by NO pathways and MMP-9. These findings provide insight into the regulation of diameters of tissue-engineered blood vessels. This is an important step toward the construction of hierarchical vascular networks within biofabricated three-dimensional systems.

Microcirculation, which connects macrocirculation and cells between arterioles and venules, plays a major role in the early onset of a variety of diseases. In this article, a dextran-induced microcirculation dysfunction (MCDF) model rats were adopted to evaluate the effects and mechanism of Salvia miltiorrhiza stem-leaf extracts based on plasma and urine metabonomics. The results showed the effective components of S. miltiorrhiza stem-leaf could significantly improve the hemorheology and coagulation index of MCDF rats and callback the expression of endothelin-1 (ET-1), induciblenitric oxide synthase (iNOS), vascularendothelial growth factor (VEGF), P-Selectin, thromboxane A2, 6-keto-PGF 1α , TNF-α, and interleukin-1β to control group in MCDF rats. The decrease of microvessel density (MVD) in lung and thymus caused by MCDF was upgraded by Salvia miltiorrhiza stem-leaf. Based on the plasma and urine metabolic data, 20 potential biomarkers were identified. These biomarkers are mainly related to linoleic acid metabolism, glutathione metabolism, pantothenate and coenzyme A biosynthesis, pentose and glucuronate interconversions, pyruvate metabolism, glyoxylate and dicarboxylate metabolism, beta-alanine metabolism, and citrate cycle. The results indicated that the effective components of S. miltiorrhiza stem-leaf can improve the hemorheological disorder and vascular endothelial function. Meanwhile, the effective components can regulate potential biomarkers and correlated metabolic pathway, which can provide guidance for the research and development of new drugs for MCDF., (© 2020 John Wiley & Sons, Ltd.)

Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low-glycemic index isomaltulose (Palatinose™) with that of sucrose in modulating EF, as assessed by flow-mediated dilation (FMD). In this double-blinded cross-over study, 80 overweight mildly hypertensive subjects were randomized to receive 50 g of either isomaltulose or sucrose. On two non-consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0-T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltulose compared to sucrose (ΔFMD = -0.003% and -0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltulose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p = 0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r-range = -0.20 to -0.23, p < 0.1). Sub-analysis suggested a lower FMD in insulin-resistant (IR) compared to insulin-sensitive subjects. Isomaltulose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltulose to preserve the endothelial function postprandially and consequently play a favorable role in cardiovascular health., Competing Interests: E.d.G. has honorary consultancies with Atlantia Food CRO, COLSWE environmental sensors, AiREAS corporation and Municipality of Eindhoven, and the Departments of Clinical Epidemiology, Biostatistics and Bioinformatics, and Gastroenterolog, of the Amsterdam UMC—Academic Medical Centre. E.d.G. receives writing fees from Up-to-Date in Cardiology (Wolters Kluwer). E.d.G. is owner and employee of Imagelabonline & Cardiovascular. Imagelabonline served as a subcontractor for Atlantia Food CRO, Cork, Ireland in the present study. E.d.G. also received research grants from the AMC Research Foundation, Academic Medical Center—Amsterdam UMC, Bioactor BV, Pfizer, LSP-Quartz, and the Municipality of Eindhoven. Otherwise, E.d.G. has no disclosures to make. S.T. and L.S. are employees of BENEO GmbH/Südzucker Group. In this double-blinded study, source data were provided by Atlantia Food Clinical Trials CRO, Cork, Ireland. Primary data analysis and report generation were undertaken by Atlantia Food Clinical Trials CRO independently from the sponsor. The statistical analyses of this publication have been developed for BENEO GmbH, which was also the exclusive sponsor of the project. BENEO GmbH reserves the exclusive right to use the results and data for possible Health Claim requests.

Background: Severe bacterial infections initiate inadequate inflammation that leads to disseminated intravascular coagulation and death., Objectives: To evaluate the influence of bacterial infection on blood viscosity and red blood cells (RBCs) morphology, and the ability of Calotropis procera proteins (CpLP) to prevent the patho-hemorheology in infected animals., Methods: Rheology of blood, atomic force microscopy measurements on specific blood elements and blood count were performed to examine changes in blood viscosity, RBCs morphology, platelets activation, and RBCs indices., Findings: Infected mice hold their blood rheological behaviour as compared to that of the control group. However, they presented hyperactivated platelets, RBCs at different stages of eryptosis, and variation on RBCs indices. CpLP administration in healthy animals altered blood behaviour from pseudoplastic to Bingham-like fluid. Such effect disappeared over time and by inhibiting its proteases. No alterations were observed in RBCs morphology or platelets. Treatment of infected animals with CpLP prevented the changes in RBCs indices and morphology., Main Conclusions: The inflammatory process triggered by bacterial infection induced pathological changes in RBCs and platelets activation. Treatment of infected animals with CpLP prevented the emergence of RBCs abnormal morphology and this may have implications in the protective effect of CpLP, avoiding animal death.

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.

Background New therapeutic strategies, such as the use of agents to correct rheological disorders, are needed for the prevention and treatment of angiopathy in diabetic patients. The aim of this work was to study the antihyperglycaemic, haemorheologic and antioxidant activities of an extract from the flowering plant Lychnis chalcedonica L. (ELC) and 20-hydroxyecdysone using the streptozotocin-induced model of diabetic rats. Methods The streptozotocin-induced model of diabetes was produced using streptozotocin at a dose of 50 mg/kg (ip). Animals from the experimental groups were treated with ELC (150 mg/kg) or 20-hydroxyecdysone (1.1 mg/kg) intragastrically in 1% aqueous starch mucilage daily, for 14 days; rats of control groups received an equal volume of starch mucilage. The following parameters were measured: glucose concentration (GC) in blood, whole blood viscosity (WBV), conjugated dienes in RBC membranes. Macro- and microrheological indicators (viz. plasma viscosity, haematocrit, RBC aggregation (T1/2) and the RBC elongation index (EI)) were additionally measured in rats that received ELC, and in the control group. Results After treatment with ELC, the GC in rats was 19% lower than that in the control group (14.7 ± 0.9 mM compared to 18.2 ± 1.1 mM). Rats with streptozotocin-induced diabetes have hyperviscosity syndrome, which is characterized by increased WBV, increased RBC aggregation and decreased deformability. ELC treatment reduced WBV at shear rates of 10-90 s-1 by 5-8%, and T1/2 and EI in the experimental group were 31% and 5-10% higher compared to the control group. 20-Hydroxyecdysone decreased WBV at shear rates of 10-90 s-1 by 3-11%. Finally, ELC and 20-hydroxyecdysone lowered the content of conjugated dienes by 27% and by 26% compared to the control groups. Conclusion In the streptozotocin-induced diabetic rat model, ELC showed measurable antihyperglycaemic activity; ELC and 20-hydroxyecdysone demonstrated similar haemorheological, and antioxidant activities.

The present study focused on the effect of paeonol, one of the main components of Guizhi Fuling Pill, on blood pressure, cerebral blood flow, and vascular endothelium injury in spontaneously hypertensive rats to provide theoretical basis for the treatment of hypertension. After treatment with paeonol, the mean arterial pressure (MAP) of LSHRT and HSHRT rats decreased gradually with the prolongation of treatment time. The systolic blood flow velocity (Vs), diastolic blood flow velocity (Vd) and mean blood flow velocity (Vm) were significantly increased after paeonol treatment ( p < 0.05). Paeonol effectively improved the blood pressure and increased the cerebral blood flow velocity in spontaneously hypertensive rats. This may be related to the fact that paeonol reduced the blood viscosity and the oxidative stress and improved the antioxidant capacity. Moreover, paeonol protected vascular endothelial cells and reduced vascular endothelial injury in spontaneously hypertensive rats.

Danshen (salvia miltiorrhiza) and honghua(Carthamus tinctorius) were traditional herb pair with promoting blood circulation and removing blood stasis actions, in China. Both were widely used to treat cardiovascular diseases (CVD) for hundreds years, especially shown definite advantage in the treatment of ischemic heart disease (IHD). However, the mechanism of danshen-honghua herb pair (DHHP) in the treatment of IHD was still unclear. This study was focused on examining the effects and possible mechanisms of DHHP in rats with acute myocardial ischemia induced by isoproterenol (ISO). The results suggested that DHHP significantly ameliorated the myocardial tissue abnormalities, notablely inhibited the elevation of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), creatinekinase isoenzyme (CK-MB) and cardiac troponin T (CTn-T) in plasma, obviously decreased the plasma levels of Tumor Necrosis Factor α (TNF-α), outstandingly inhibited the reduction of superoxide dismutase (SOD), catalase (CAT) caused by ISO, significantly inhibited the high expression of Bcl-2 assaciated X protein (Bax) and nuclear transcriptionfactor-κBP65 (NF-κBP65) protein, significantly induced the low expression of B-cell lymphoma-2 (Bcl-2) protein in acute myocardial ischemia rats. DHHP can obviously ameliorate hemodynamic parameters. In summary, DHHP can significantly improve myocardial ischemia in acute myocardial ischemia model rats caused by ISO. Anti-free radicals, anti-peroxidation, inhibition of cell apoptosis and anti- inflammation maybe are the potential mechanisms of DHHP anti-myocardial ischemia in acute myocardial ischemia rats in duced by ISO., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Hemorheological properties represent significant contributors in the pathogenesis of cardiovascular diseases. As plasma vitamin C is inversely associated with blood viscosity in humans, we aimed to characterize the effect of vitamin C supplementation on hemorheology with an emphasis on erythrocyte functions. Twenty young healthy volunteers were asked to take vitamin C (1000 mg per day) for 3 weeks. We observed beneficial effect of intervention on multiple hemorheological parameters: whole blood viscosity in the range of medium to high shear rates, Casson yield stress, complex viscosity, and storage and loss moduli. As erythrocyte properties play a significant role in hemorheology, we characterized their deformability, nitric oxide production, and sodium pump activity in erythrocyte membranes. We can conclude that observed promotion in whole blood rheology may be consequence of improved erythrocyte functionality as concerns their ability to pass through narrow capillaries of the microcirculation, nitric oxide production, and sodium pump activity. Parameters reflecting oxidative stress and antioxidant status in plasma were not affected by our intervention. As improvement in hemorheology may play an important role in cardioprotection, it would be challenging to investigate the vitamin C supplementation to patients suffering from microcirculatory disturbances and worsened organ perfusion in the case of cardiovascular diseases.

Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device-related infections and provide insight into the development of pump thrombosis. Biomaterials-DLC: diamond-like carbon-coated stainless steel; Sap: single-crystal sapphire; and Ti: titanium alloy (Ti 6 Al 4 V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s -1 or 1000 s -1 ). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro-inflammatory cytokines. L-selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L-selectin expression. Sap and Ti blunted the LPS-stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Danshen (Salvia miltiorrhiza, DS) and Honghua (Carthamus tinctorius, HH) are commonly used traditional Chinese medicines for activating blood and removing stasis, and DS-HH (DH) herbal pair had potential synergistic effects on promoting blood circulation. Therefore, it is essential to make clear the active components of this herbal pair for better understanding their potential synergistic effects., Purpose: To comprehensively evaluate the activity of DH herbal pair on physiological coagulation system of rats, and seek their potential active components by spectrum-effect relationship analysis., Methods: The water extracts of DH herbal pair with different proportions (DS: HH = 1:1, 2:1, 3:1, 5:1, 1:5 and 1:3) were prepared. Male Sprague-Dawley rats were randomly divided into eight groups: blank group, model group, model + 1:1 (DH) group, model + 2:1 group, model + 3:1 group, model + 5:1 group, model + 1:5 group and model + 1:3 group. The intragastric administration was performed for eight times with 12 h intervals. SC40 semi-automatic coagulation analyzer was employed to determine coagulation indices. Meanwhile, HPLC and LC-MS were applied for chemical analyses of DH extracts. Finally, the active ingredients were screened by spectrum-effect relationship analysis and the activities of major predicted compounds were validated in vitro., Results: Different proportions of DH extracts could significantly prolong thrombin time (TT) and activated partial thromboplastin time (APTT), increase prothrombin time (PT) and decrease fibrinogen (FIB) content, reduced whole blood viscosity (WBV) and plasma viscosity (PV), decreased erythrocyte sedimentation rate blood (ESR) compared with model group. Furthermore, fifteen highly related components were screened out by the spectrum-effect relationship and LC-MS analysis, of which caffeic acid, salvianolic acid B, hydroxysafflor yellow A and lithospermate acid had significant blood-activing effect by prolong APTT and decrease FIB content at high (0.6 mM), medium (0.3 mM) and low (0.15 mM) (except lithospermate acid) concentrations in vitro., Conclusions: DH herbal pair showed strong blood-activating effect on blood stasis rat through regulating the parameters involved in haemorheology and plasma coagulation system. Four active compounds, caffeic acid, salvianolic acid B, hydroxysafflor yellow A and lithospermate acid predicted by spectrum-effect relationship analysis had good blood-activating effect. Therefore, spectrum-effect relationship analysis is an effective approach for seeking active components in herbal pairs., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes., Objective: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE)., Methods: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2max and 2-min active recovery at 40% of vVO2max. Three blood samples were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties., Results: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P < 0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P > 0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P < 0.05)., Conclusions: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men.

Rhizome of Curcuma wenyujin , which is called EZhu in China, is a traditional Chinese medicine used to treat blood stasis for many years. However, the underlying mechanism of EZhu is not clear at present. In this study, plasma metabolomics combined with network pharmacology were used to elucidate the therapeutic mechanism of EZhu in blood stasis from a metabolic perspective. The results showed that 26 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees by EZhu preadministration. Metabolic pathway analysis showed that the improvement of blood stasis by Curcuma wenyujin rhizome was mainly related to lipid metabolism (linoleic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolisms (tryptophan metabolism, lysine degradation). The component-target-pathway network showed that 68 target proteins were associated with 21 chemical components in EZhu. Five metabolic pathways of the network, including linoleic acid metabolism, sphingolipid metabolism, glycerolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis, were consistent with plasma metabolomics results. In conclusion, plasma metabolomics combined with network pharmacology can be helpful to clarify the mechanism of EZhu in improving blood stasis and to provide a literature basis for further research on the therapeutic mechanism of EZhu in clinical practice.

Estetrol (E4) is a natural estrogen synthesized exclusively during pregnancy by the human fetal liver, and the physiological role of this hormone is unknown. Interestingly, E4 was recently evaluated in preclinical and phase II-III clinical studies in combination with a progestin, with the advantage to not increase the circulating level of coagulation factors, at variance to oral estradiol or ethinylestradiol. Here, we evaluated the effect of E4 on hemostasis and thrombosis in mouse. Following chronic E4 treatment, mice exhibited a prolonged tail-bleeding time and were protected from arterial and also venous thrombosis in vivo. In addition, E4 treatment decreased ex vivo thrombus growth on collagen under arterial flow conditions. We recently showed that E4 activates uterine epithelial proliferation through nuclear estrogen receptor (ER) α. To analyze the impact of nuclear ERα actions on hemostasis and thrombosis, we generated hematopoietic chimera with bone marrow cells deficient for nuclear ERα. E4-induced protection against thromboembolism was significantly reduced in the absence of hematopoietic nuclear ERα activation, while the increased tail-bleeding time was not impacted by this deletion. In addition to its "liver friendly" profile described in women, our data shows that E4 has anti-thrombotic properties in various mouse models. Altogether, the natural fetal estrogen E4 could represent an attractive alternative to classic estrogens in oral contraception and treatment of menopause., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Determine the effect of fetal hemoglobin (HbF) and α-thalassemia on red blood cell (RBC) deformability of patients with sickle-cell anemia (SCA) with and without hydroxyurea (HU)., Methods: Adult patients were enrolled in the Sickle Cell Program of the Cardeza Foundation (Thomas Jefferson University) and were followed up prospectively during the period in which the Multicenter Study of Hydroxyurea (MSH) in patients with SCA was conducted. Ninety-one patients did not receive HU, 20 patients were enrolled in MSH, and 10 patients were enrolled in an open-label study of HU in SCA. Of the 20 patients enrolled in MSH, 11 took HU and nine took placebo. Control group included 113 normal individuals. Red blood cell deformability index (DI) was measured by ektacytometry., Results: Patients with SCA taking HU (n = 21) had higher DI than those taking placebo (n = 9) or who were not taking this therapy (n = 91). In patients without therapy, those with α-thalassemia (n = 31) had higher DI than those without. We showed a significant positive correlation between the level of HbF and DI. SCA patients without α-thalassemia and HbF <10% (n = 48) had lower DI than patients with α-thalassemia and HbF <10% (n = 23) and patients with (n = 8) or without α-thalassemia but with HbF >10% (n = 12). DI measured in patients without α-thalassemia and HbF >10% was higher than in the three other subgroups., Conclusion: Elevated levels of HbF with or without HU and α-thalassemia improve sickle RBC rheology, which, in turn, improve the clinical picture of SCA., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Many pathological mechanisms are involved in the development of arterial hypertension; disturbance of the rheological properties of blood and microvascular rarefaction are among those mechanisms., Objective: The effect of p-tyrosol (Tyr) on hemorheological parameters and microvascularization in the cerebral cortex of spontaneously hypertensive rats (SHRs) at the stage of blood pressure rising (5-11 weeks) was studied., Methods: Blood viscosity (BV), plasma viscosity (PV), hematocrit, erythrocyte aggregation and deformability, the oxygen transport capacity index (OTCI), and the capillary network in the cerebral cortex after the course of treatment of Tyr (50 mg/kg daily i.g. for 6 weeks) were studied. Control normotensive Wistar-Kyoto (WKY) rats and control SHRs received an equivalent amount of 1% starch mucilage., Results: In comparison with WKY rats, disturbances of rheological blood parameters and a decrease in OTCI were revealed in control SHRs at the 11 weeks of life. By the end of the experiment, brain microvascular rarefaction was observed in the control SHRs (the average density of the capillary bed was reduced due to a decrease in the number of capillaries with a diameter of 3-7 μm). In SHRs rats treated with Tyr, BV and PV, the indices of erythrocyte aggregation were lower, and OTCI was higher in comparison with control SHRs. The density of the capillary network and the number of capillaries of 3-7 μm in the cerebral cortex of SHRs rats receiving Tyr were significantly higher than the corresponding values in control SHRs., Conclusion: When Tyr is administered to young SHRs during the development of hypertension, it limits the development of hyperviscosity syndrome, improves the oxygen transport capacity and eliminates microvascular rarefaction in the cerebral cortex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

When hydrophobically modified chitosan (HM-CHI) comes into contact with red blood cells (RBCs), it can cause agglomeration. This property leads HM-CHI to be a potential agent to form a rapid haemostatic plug to stop bleeding at wound sites. In this study, we investigated the properties of the HM-CHI biopolymer to act as an agent that rapidly clots blood. We have examined the synthesis and structural characteristics of HM-CHI - blood substances using X-ray diffraction, infrared spectroscopy and elemental analysis. To understand the rheological behaviour of RBCs within HM-CHI, we have studied the effects of HM-CHI on RBC aggregation and morphology using a rheometer and scanning electron microscopy (SEM), respectively. When mixed with sodium citrate, HM-CHI rapidly transformed human blood into an elastic gel. In contrast, un-modified chitosan (i.e. without hydrophobes) was unable to clot blood. The hydrophobias within HM-CHI entered into the RBC membranes and connected to the cells by a sample-spanning network, which subsequently led to the formation of an elastic gel. The gelling ability of HM-CHI is similar to that of fibrin-based sealants, but at a much lower cost and greater availability.

A solid tumor is like an aberrant organ - comprised of cancer cells and a variety of host cells embedded in an extracellular matrix - nourished by blood vessels and drained by lymphatic vessels. In its journey from the blood stream to cancer cells, a therapeutic agent must cross the vessel wall and the extracellular matrix that cancer cells are ensconced in. Growth of tumors in a confined space along with deposition of matrix components, including collagen (yellow) and hyaluronan (pink), increases 'solid stress', which compresses blood and lymphatic vessels and impairs their function. The leakiness of tumor vessels also impairs tumor blood flow and increases 'intratumor fluid pressure'. The abnormal blood flow not only impedes drug delivery, but the resulting hypoxia also aids tumor invasion, metastasis, immunosuppression, inflammation, fibrosis, and treatment resistance. Engineers and physical scientists have dissected the molecular, cellular, and physical mechanisms underlying these abnormalities and developed a number of strategies to reengineer the tumor microenvironment to overcome these barriers and thus improve delivery and efficacy of treatments. Finally, these strategies have been translated from bench to bedside for treatment of cancer and have the potential to improve the treatment outcome for many diseases characterized by an abnormal microenvironment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Injection of recombinant tissue plasminogen activator (rt-PA) is the standard drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and limited efficiency even at high doses. Polysaccharide-poly(isobutylcyanoacrylate) nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin expressed by activated platelets in the thrombus. Solid spherical fluorescent nanoparticles with a hydrodynamic diameter of 136 ± 4 nm were synthesized by redox radical emulsion polymerization. The clinical rt-PA formulation was successfully loaded by adsorption on aminated nanoparticles and able to be released in vitro. We validated the in vitro fibrinolytic activity and binding under flow to both recombinant P-selectin and activated platelet aggregates. The thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by monitoring the platelet density with intravital microscopy. This study supports the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This work establishes the proof-of-concept of fucoidan-based carriers for targeted thrombolysis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Essentials von Willebrand factor (VWF) function is shear stress dependent. Platelet accumulation in a microfluidic assay correlates with VWF levels. The microfluidic assay discriminates type 1 von Willebrand disease from healthy controls. The microfluidic flow assay detects responses to therapeutic intervention (DDAVP)., Summary: Background von Willebrand disease (VWD) is a mucocutaneous bleeding disorder with a reported prevalence of 1 in 10 000. von Willebrand factor (VWF) function and platelet adhesion are regulated by hemodynamic forces that are not integrated into most current clinical assays. Objective We evaluated whether a custom microfluidic flow assay (MFA) can screen for deficiencies in VWF in patients presenting with mucocutaneous bleeding. Methods Whole blood from individuals with mucocutaneous bleeding was assayed in a custom MFA. Results Thirty-two patients with type 1 VWD (10/32) or reported mucocutaneous bleeding were enrolled. The platelet adhesion velocity (r = 0.5978 for 750 s -1 and 0.6895 for 1500 s -1 ) and the maximum platelet surface area coverage (r = 0.5719 for 750 s -1 and 0.6633 for 1500 s -1 ) in the MFA correlated with VWF levels. Furthermore, the platelet adhesion velocity at 750 s -1 (type 1 VWD, mean 0.0009761, 95% confidence interval [CI] 0.0003404-0.001612; control, mean 0.003587, 95% CI 0.002455-0.004719) and at 1500 s -1 (type 1 VWD, mean 0.0003585, 95% CI 0.00003914-0.0006778; control, mean 0.003132, 95% CI 0.001565-0.004699) differentiated type 1 VWD from controls. Maximum platelet surface area coverage at 750 s -1 (type 1 VWD, mean 0.1831, 95% CI 0.03816-0.3281; control, mean 0.6755, 95% CI 0.471-0.88) and at 1500 s -1 (type 1 VWD, mean 0.07873, 95% CI 0.01689-0.1406; control, mean 0.6432, 95% CI 0.3607-0.9257) also differentiated type 1 VWD from controls. We also observed an improvement in platelet accumulation after 1-desamino-8-d-arginine vasopressin (DDAVP) treatment at 1500 s -1 (pre-DDAVP, mean 0.4784, 95% CI 0.1777-0.7791; post-DDAVP, mean 0.8444, 95% CI 0.7162-0.9726). Conclusions These data suggest that this approach can be used as a screening tool for VWD., (© 2017 International Society on Thrombosis and Haemostasis.)

The purpose of this study is to develop a new method of preparing salvianolic acid extracts (SAE) water-in-oil-in-water (W/O/W) multiple emulsion (ME). SAE injection is used in the treatment of brain infarct and promotion of blood circulation in China. However, the injection is not convenient, and the oral preparation has poor bioavailability. Hence, a new preparation that is convenient and stable with good biological availability is required. SAE ME was prepared by two-step emulsification method. Combined with single-factor investigation and orthogonal test, the embedding rate and centrifugal retention rate were taken as the comprehensive indexes to optimize the formulation of SAE ME. The ME size was tested by laser particle size analyzer. The pharmacokinetic studies were conducted in Sprague-Dawley rats with HPLC-MS/MS method. The blood coagulation and hemorheology tests were conducted to assess the effect of preparation in rats. The best preparation technique for SAE ME is by the use of trospium chloride; SAE represent 12% of water in the phase, lipophilic emulsifier hydrophilic lipophilic balance value=4.3, lipophilic emulsifier is 20% of the oil phase. The median diameter of particle is (0.608±0.05) µm and the C max of ME is 3-fold higher compared to C max of free drug. The oral biavailability of ME is 26.71-fold higher than that of free drug with good effect on blood circulation. SAE ME is stable hence, improves the biological availability and slows down drug release.

Objective: To investigate the effect of baicalin on the changes in hemorheology and its mechanism during the development of Acute Respiratory Distress Syndrome(ARDS) induced by oleic acid (OA) in rats. Methods: Rats were randomized into 3 groups: control, ARDS (OA induction, 0.12 mg/kg) and ba-icalin-treated group (300 mg/kg). The blood samples were collected at 30 min, 1, 2, 3, 6, 12 and 6 h after OA injection. The whole blood viscosity, plasma viscosity, Maximum erythrocyte deformability index (DImax) were detected. Meanwhile, blood gas analysis and Routine blood test were also performed. Results: The level of arte-rial oxygen partial pressure and oxygenation index decreased (P<0.01 vs. control) and oxygenation index (178 mm Hg, 1 mm Hg=0.133 kPa) reached the diagnostic standard of ARDS at 2 h in ARDS group. In baicalin-treated group, the level of arterial oxygen partial pressure and oxygenation index increased versus the ARDS group. The platelet count (PLT) decreased in baicalin-treated and ARDS groups. Compared with the ARDS group, the level of PLT increased significantly in baicalin-treated group at 30min, 1, 2, and 3 h. Hematocrit (HCT) increased in baicalin-treated and ARDS groups. Compared with the ARDS group, the level of HCT de-creased significantly in baicalin-treated group at 2, 3, 6 and 12 h. Meanwhile, all the index of hemorheology improved in baicalin-treated group. Conclusion: Baicalin may improve hypoxemia of ARDS induced by OA in rats. It may be due to the Improvement of microcirculation of lung.

Shexiang Tongxin Dropping Pill (STP) is an established traditional Chinese medicine that is widely used for the treatment of ischemic heart disease (IHD), although its mechanisms remain unclear. The present study investigated the protective effects of STP following pituitrin (PTT)‑induced myocardial ischemia in rats. ST‑segment elevation, blood rheology, and the serum levels of creatine kinase‑MB (CK‑MB) and lactate dehydrogenase (LDH) were measured. Following heart excision, histological analysis using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed. The mRNA expression levels of B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax) were determined using reverse transcription‑quantitative polymerase chain reaction, and their protein expression was detected using immunohistochemistry. The results demonstrated that STP treatment protected against ST elevation, lowered whole blood viscosity, and reduced the serum levels of CK‑MB and LDH following acute myocardial ischemia. In addition, STP treatment restored the histopathological change following PTT‑induced myocardial ischemia, and resulted in downregulated expression of Bax and upregulated expression of Bcl‑2 in myocardial tissue. The present study demonstrates the cardioprotective ability of STP in a rat model of myocardial ischemic injury, which may be attributed to its anti‑apoptotic properties. The cardioprotective properties of STP require further investigation to determine whether it may be used for the clinical treatment of IHDs.

Spider silk became one of the most-researched biomaterials in the last years due to its unique mechanical strength and most favourable chemical composition for tissue engineering purposes. However, standardized analysis of cytocompatibility is missing. Therefore, the aim of this study was to investigate hemolysis, cytotoxicity of native spider silk as well as influences on the cell culture medium. Changes of cell culture medium composition, osmolarity as well as glucose and lactate content were determined via ELISA measurement. Possible hemolysis and cytotoxicity in vitro of spider silk were performed via measurement of hemoglobin release of human red blood cells or relative metabolic activity of L929 fibroblasts, respectively, according to international standard procedures. In ELISA measurement, no significant changes in medium composition could be found in this study. Spider silk was not hemolytic in direct and indirect testing. However, a borderline cytotoxicity according to definitions was found in indirect cytotoxicity testing. Nevertheless, in direct cytotoxicity testing, relative metabolic activity measurement revealed that spider silk is not cytotoxic under these conditions. This is the first study to conduct standardized tests regarding cytotoxicity and hemolysis of native spider silk, which might be considered inert in cell culture. As neither hemolysis nor cytotoxicity was found in direct contact in standardized procedures, safety in biomedical applications may be assumed. The indirect cytotoxicity seems to play a minor role in vivo. However, a borderline toxicity was revealed, suggesting potential leachables not yet identified. Displays one of the weaving frames used in this study after seeding with the single drop technique described herein.

Acute limb ischemia is one of the most common peripheral arterial disease, while surgical restoration of blood flow often results in ischemia/reperfusion (I/R) injury. Our previous study revealed the inflammation intensity in arterial tissue, characterized by expression of high mobility group box protein 1 (HMGB1), was contrary to the fluctuation of hemodynamics in reperfusion limbs in a rat model. This study meant to clarify the role of HMGB1 during this process. Laser Doppler perfusion imaging evaluated limb hemodynamics in mean and max perfusion unit (PU). Femoral arterial tissue was collected for molecular biology examination. The results revealed that HMGB1 promoted vascular structure remodeling and vasomotor dysfunction during acute I/R, characterized by degradation of collagenous fibers, disruption of elastic lamellae, intensive inflammation and phenotype transfer of smooth muscle cells. Blockade of HMGB1 preserved vascular homeostasis and improved PUs (P meanPU <0.001, P maxPU <0.001). The elevated expression of TNF-α, IL-6, ICAM, VCAM, MMP-2, MMP-9, α-SM actin correlated with HMGB1 positively. In conclusion, HMGB1 promoted vascular remodeling and dysfunction via initiating an inflammation cascade during I/R. Blockade of HMGB1 would preserve vascular homeostasis and facilitate the blood perfusion of ischemic limb., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/aim: Septic shock is an important health problem that vastly alters cardiovascular and hemodynamic status. Increased production of nitric oxide (NO) and endothelin is a counterpart of this endotoxemic state. This study was conducted to test the hypothesis that nonselective NO synthesis blocker (L-NAME), inducible NO synthesis blocker (L-canavanine), or endothelin receptor antagonist (bosentan) will reverse the effects of sepsis on hemorheological parameters., Materials and Methods: Forty-eight male Sprague-Dawley rats were used in 8 groups: saline (control), endotoxin, bosentan, L-NAME, L-canavanine, endotoxin + bosentan, endotoxin + L-NAME, and endotoxin + L-canavanine. Blood was withdrawn at the 4th hour of endotoxemic state. Erythrocyte deformability and erythrocyte aggregation were determined by laser-assisted optical rotational cell analyzer at 37 °C. Plasma viscosity (mPa.s) was measured by a cone-plate viscometer with 0.5 mL of plasma., Results: Endotoxin administration significantly increased aggregation half-time and lowered erythrocyte aggregation amplitude and aggregation index compared to the control, indicating a slower and weaker aggregation pattern. L-NAME and L-canavanine alleviated the effects of endotoxin on erythrocyte aggregation without altering the values in the control animals. However, bosentan did not perform such a restoration., Conclusion: This finding suggests that these restoration effects of the blockers occur via their modulation of nitric oxide synthesis rather than through the endothelin pathway.

Peripheral artery disease is an atherosclerotic stenosis in the peripheral vasculature that is typically treated via percutaneous transluminal angioplasty. Deployment of the angioplasty balloon damages the endothelial layer, exposing the underlying collagen and allowing for the binding and activation of circulating platelets which initiate an inflammatory cascade leading to eventual restenosis. Here, we report on collagen-binding sulfated poly(N-isopropylacrylamide) nanoparticles that are able to target to the denuded endothelium. Once bound, these nanoparticles present a barrier that reduces cellular and platelet adhesion to the collagenous surface by 67% in whole blood and 59% in platelet-rich plasma under biologically relevant shear rates. In vitro studies indicate that the collagen-binding nanoparticles are able to load and release therapeutic quantities of anti-inflammatory peptides, with the particles reducing inflammation in endothelial and smooth muscle cells by 30% and 40% respectively. Once bound to collagen, the nanoparticles increased endothelial migration while avoiding uptake by smooth muscle cells, indicating that they may promote regeneration of the damaged endothelium while remaining anchored to the collagenous matrix and locally releasing anti-inflammatory peptides into the injured area. Combined, these collagen-binding nanoparticles have the potential to reduce inflammation, and the subsequent restenosis, while simultaneously promoting endothelial regeneration following balloon angioplasty., Statement of Significance: In this manuscript, we present our work on the development and characterization of a novel temperature sensitive collagen-binding nanoparticle system. We demonstrate that when bound to a collagenous matrix, the nanoparticles are able to promote endothelial migration while avoiding cellular uptake. We also show that the nanoparticles are able to reduce inflammation via the release of anti-inflammatory peptides which, when combined with its ability to inhibit platelet binding, could lead to reduced intimal hyperplasia following balloon angioplasty. The drug delivery platform presented represents a unique dual therapy biomaterial wherein the nanoparticle itself plays a crucial role in the system's overall therapeutic potential while simultaneously releasing anti-inflammatory peptides., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The most common form of hypertension in young adults is isolated diastolic hypertension. Diastolic arterial pressure is determined by the total peripheral resistance and depends on both vascular hindrance and blood viscosity. The aim of our work was to study the efficiency of pentoxifylline (PTX) in young spontaneously hypertensive rats (SHRs) during the development of arterial hypertension. The effects of a treatment course with PTX (100 mg/kg/day p.o. for 6 weeks, from 5 to 11 weeks old) on the mean, systolic, and diastolic blood pressure (BP); stroke volume; cardiac output; total peripheral resistance (TPR); whole blood viscosity (BV); plasma viscosity; hematocrit; RBC aggregation and deformability; local cerebral blood flow (lCBF); and microvascularization of the visual cortex were studied in SHRs in comparison with control SHRs and Wistar Kyoto rats. PTX-treated SHRs had significantly lower systolic, diastolic, and mean BP (by 24%, 26%, and 15%, respectively) and BV (by 5-9%) and a higher erythrocyte deformability index (by 1.5-2%), lCBF (by 42%), average diameter of capillaries (by 11%), density of the capillary network (by 23%), and percentage of capillaries with a diameter of 3-7 µm in comparison with control SHRs. In conclusion, PTX exerted positive effects on the hemodynamic, hemorheological, and microcirculatory parameters in SHRs during the development of arterial hypertension.

Background: Diuretics are the first choice as an antihypertensive, because of its efficacy and cost, however its mechanism of action is not well understood. The aim of this work was to analyze the hemorrheological effect of the diuretics as vasodilators in patients with newly diagnosed arterial hypertension., Methods: Patients with hypertension were given diet and exercise recommendations and 25 mg of chlorthalidone per day were prescribed; Hemoglobin/hematocrit, viscosity, and basal nitric oxide (ON) were determined at 15 and 45 days and compared with healthy subjects., Results: We included 28 patients with average age of 48 years old; systolic blood pressure in the treated patients decreased from baseline at 15 days from 130 to 119 mm Hg and at 114 mmHg at 15 to 45 days; diastolic blood pressure decreased from baseline at 15 days from 103 to 97 mm Hg, and at 93 mmHg at 15 to 45 days. The hematocrit increased in both men and women with a statistical significance of the baseline period at 15 days, after that, it remained without significative changes. The viscosity increased similarly to the hematocrit, which conditioned the ON elevation., Conclusions: The increase in hematocrit due to diuretic caused an increase in blood viscosity, which led to an increase in nitric oxide, resulting in lower blood pressure.

The pharmacodynamics of phytoestrogens representing nonsteroidal compounds of plant origin with variable affinity to estrogen receptor subtypes has been studied. Clinical and experimental data on the mechanisms of action of phytoestrogens of the isoflavone and lignan classes are presented and their effects ca- pable of reducing the risk of cardiovascular disease development in women with climacteric syndrome and in experimental hypoestrogenemia are considered.

The role of the sarco-endoplasmic reticulum calcium (Ca(2+)) adenosine triphosphatase (ATPase) 3 (SERCA3) in platelet physiology remains poorly understood. Here, we show that SERCA3 knockout (SERCA3(-/-)) mice exhibit prolonged tail bleeding time and rebleeding. Thrombus formation was delayed both in arteries and venules in an in vivo ferric chloride-induced thrombosis model. Defective platelet adhesion and thrombus growth over collagen was confirmed in vitro. Adenosine 5'-diphosphate (ADP) removal by apyrase diminished adhesion and thrombus growth of control platelets to the level of SERCA3(-/-) platelets. Aggregation, dense granule secretion, and Ca(2+) mobilization of SERCA3(-/-) platelets induced by low collagen or low thrombin concentration were weaker than controls. Accordingly, SERCA3(-/-) platelets exhibited a partial defect in total stored Ca(2+) and in Ca(2+) store reuptake following thrombin stimulation. Importantly ADP, but not serotonin, rescued aggregation, secretion, and Ca(2+) mobilization in SERCA3(-/-) platelets, suggesting specificity. Dense granules appeared normal upon electron microscopy, mepacrine staining, and total serotonin content, ruling out a dense granule defect. ADP induced normal platelet aggregation, excluding a defect in ADP activation pathways. The SERCA3-specific inhibitor 2,5-di-(tert-butyl)-1,4-benzohydroquinone diminished both Ca(2+) mobilization and secretion of control platelets, as opposed to the SERCA2b inhibitor thapsigargin. This confirmed the specific role of catalytically active SERCA3 in ADP secretion. Accordingly, SERCA3-dependent Ca(2+) stores appeared depleted in SERCA3(-/-) platelets. Finally, αIIbβ3 integrin blockade did not affect SERCA3-dependent secretion, therefore proving independent of αIIbβ3 engagement. Altogether, these results show that SERCA3-dependent Ca(2+) stores control a specific ADP secretion pathway required for full platelet secretion induced by agonists at low concentration and independent of αIIbβ3., (© 2016 by The American Society of Hematology.)

Background: Based on the prodrug principle, aspirin and eugenol, as starting precursors, were esterified to synthesize aspirin eugenol ester (AEE). The aim of the present study was to evaluate the antithrombotic effect of AEE in an animal disease model. In order to compare the therapeutic effects of AEE and its precursors, aspirin, eugenol and a combination of aspirin and eugenol were designed at the same molar quantities as the AEE medium dose in the control group., Methods: After oral administration of AEE (dosed at 18, 36 and 72 mg/kg) for seven days, rats were treated with k-carrageenan to induce tail thrombosis. Following the same method, aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5 % CMC-Na (30 mg/kg) were administered as control drug. Different drug effects on platelet aggregation, hemorheology, TXB2/6-keto-PGF1α ratio and blood biochemistry were studied., Results: AEE significantly inhibited ADP and AA-induced platelet aggregation in vivo. AEE also significantly reduced blood and plasma viscosity. Moreover, AEE down-regulated TXB2 and up-regulated 6-keto-PGF1α, normalizing the TXB2/6-keto-PGF1α ratio and blood biochemical profile. In comparison with aspirin and eugenol, AEE produced more positive therapeutic effects than its precursors under the same molar quantity., Conclusion: It may be concluded that AEE was a good candidate for new antithrombotic and antiplatelet medicine. Additionally, this study may help to understand how AEE works on antithrombosis in different ways.

Amphiphilic block copolymer methoxy polyethyleneglycol-polycaprolactone (mPEG-PCL) has attracted interest in the biomedical field, due to its water solubility and biodegradability. Nevertheless, the blood safety of mPEG-PCL copolymers has not been investigated in detail. Because mPEG-PCL copolymers introduced in vivo would inevitably interact with blood tissue, an investigation of possible interactions of mPEG-PCL with key blood components is crucial. We studied the effects of two mPEG-PCL copolymer solutions on blood coagulation, the morphology and lysis of human red blood cells (RBCs), the structure of plasma fibrinogen, complement activation, and platelet aggregation. We found that higher concentrations of the mPEG-PCL copolymers impaired blood clotting, and the copolymers had little impact on the morphology or lysis of RBCs. From the spectroscopy results, the copolymers affected the local microstructure of fibrinogen. The copolymers significantly activated the complement system in a concentration-dependent way. At higher concentrations, the copolymers impaired platelet aggregation, which may have been mediated by an inhibition of the arachidonic acid pathway. These findings provide important information that may be useful for the molecular design and biomedical applications of mPEG-PCL copolymers. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 802-812, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: Postmenopausal women often develop hemorheological disorders which may affect the systemic blood circulation and present a cardiovascular risk factor., Objective: We evaluated effects of secoisolariciresinol (SECO), a phytoestrogen, on hemorheological parameters and lipid peroxidation in a model of the age-related and/or surgical menopause induced by ovariectomy in rats., Methods: Arterial blood was sampled from sham-operated female rats, ovariectomized rats (OVX), and OVX treated with SECO (OVXSECO) (20 mg/kg/day intragastrically for two weeks). Plasma estrogen concentration and the following hemorheological parameters were measured: RBC aggregation (half-time of aggregation, T1/2; amplitude of aggregation, AMP; aggregation index, AI), RBC deformability (elongation index, EI), whole blood viscosity at the shear rate of 3-300 s-1, plasma viscosity, hematocrit, plasma fibrinogen. Lipid peroxidation was evaluated by measuring conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS) in plasma., Results: Ovariectomy in rats caused a 60% decrease in plasma estrogen level and triggered the development of macro- and microhemorheological abnormalities. Blood viscosity increased by 12-31%, RBC elongation index reduced by 16-28%, and T1/2 and AI increased by 35% and 29% respectively. The increase in blood viscosity correlated predominantly with reduced RBC deformability. Plasma CD and TBARS were elevated by 47% and 104% respectively. SECO therapy for OVX rats reduced blood viscosity by 9-18% and T1/2 by 32%, and increased EI by 4-17%. SECO therapy disrupted the correlation between blood viscosity and RBC deformability. Lipid peroxidation was significantly inhibited, as shown by the reduction in CD and TBARS plasma concentrations by 89% and 70% respectively. SECO did not affect plasma viscosity, estrogen or fibrinogen levels., Conclusions: SECO treatment for OVX rats improves blood macro- and microrheological parameters, possibly through antioxidant protection of RBC.

Prevention of cardiovascular complications is one of the objectives of antihyperiensive therapy. However, the expected effect cannot be fully achieved by me- ans of the blood pressure control only. The authors studied the effect of captopril administration in SHR rats by monitoring the following parameters: arterial blood pressure, rheological properties of blood, and endothelial index of vasodilator activity (IVA), as well as their correlations. In SHR rats, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) were higher by 28 - 33% as compared to WKY rats. In comparison to normotensive animals, the blood vis- cosity (BV) at shear rates from 30 to 450 sec -1 in SHR rats was increased by 12 - 15% (p = 0.020), the aggregation of red blood cells was increased by 22% (p = 0.012), and their plasticity in the range of shear stresses within 3 - 20 Pa was decreased by 2 - 8% (p = 0.028). The IVA value in SHR rats was lower by 26 % (p = 0.030) than that in WKY rats. The administration of captopril decreased the SBP and DBP values down to the level in normotensive animals, but did not influence the rheological properties of blood and its IVA value. In WKY rats, the BV exhibited reliable correlation with IVA (with r from +0.60 ai +0.67, p <0.05) at shear rates ranging within 30 - 450 sec -1, while the rheological parameters were correlated with neither SBP nor DBP. In SHR rats, the BV corre- lated with IVA only at 450 sec -1 (with r =+0.50, p = 0.025), and there were relationships between SBP and BV (r = + 0.64, p = 0.008) and the aggregation in- dex (r = +0.69, p = 0.003). Rats treated with captopril showed no correlations between hemorheological and hemodynamic parameters. Therefore, captopril decreases the arterial blood pressure, but it also violates the contour of vascular tone regulation associated with changes in shear stress on the vascular wall, which plays an important role in ensuring adequate local blood flow.

Nanomolar intravascular concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of ischemic myocardium and limb, but the effects of DRP on the cerebral microcirculation have not yet been studied. We recently demonstrated that DRP enhance microvascular flow in normal rat brain and hypothesized that it would restore impaired microvascular perfusion and improve outcomes after focal ischemia and traumatic brain injury (TBI). We studied the effects of DRP (high molecular weight polyethylene oxide, 4000 kDa, i.v. at 2 μg/mL of blood) on microcirculation of the rat brain: (1) after permanent middle cerebral artery occlusion (pMCAO); and (2) after TBI induced by fluid percussion. Using in vivo two-photon laser scanning microscopy (2PLSM) over the parietal cortex of anesthetized rats we showed that both pMCAO and TBI resulted in progressive decrease in microvascular circulation, leading to tissue hypoxia (NADH increase) and increased blood brain barrier (BBB) degradation. DRP, injected post insult, increased blood volume flow in arterioles and red blood cell (RBC) flow velocity in capillaries mitigating capillary stasis, tissue hypoxia and BBB degradation, which improved neuronal survival (Fluoro-Jade B, 24 h) and neurologic outcome (Rotarod, 1 week). Improved microvascular perfusion by DRP may be effective in the treatment of ischemic stroke and TBI.

Echinocandins are known as effective and safe agents for the prophylaxis and treatment of different cohorts of patients with fungal infections. Recent studies revealed that certain pharmacokinetics of echinocandin antifungals might impact clinical efficacy and safety in special patient populations. The aim of our study was to evaluate echinocandin-induced aggravation of cardiac impairment in septic shock. Using an in vivo endotoxemic shock model in rats, we assessed hemodynamic parameters and time to hemodynamic failure (THF) after additional central-venous application of anidulafungin (2.5 mg/kg of body weight [BW]), caspofungin (0.875 mg/kg BW), micafungin (3 mg/kg BW), and control (0.9% sodium chloride). In addition, echinocandin-induced cytotoxicity was evaluated in isolated rat cardiac myocytes. THF of the animals in the caspofungin group (n = 7) was significantly reduced compared to that in the control (n = 6) (136 min versus 180 min; P = 0.0209). The anidulafungin group (n = 7) also showed a trend of reduced THF (136 min versus 180 min; log-rank test P = 0.0578). Animals in the micafungin group (n = 7) did not show significant differences in THF compared to those in the control. Control group animals and also micafungin group animals did not show altered cardiac output (CO) during our experiments. In contrast, administration of anidulafungin or caspofungin induced a decrease in CO. We also revealed a dose-dependent increase of cytotoxicity in anidulafungin- and caspofungin-treated cardiac myocytes. Treatment with micafungin did not cause significantly increased cytotoxicity. Further studies are needed to explore the underlying mechanism., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

Aim: To investigate RBC-NOS dependent NO signaling during in vivo RBC aging in health and disease., Method: RBC from fifteen healthy volunteers (HC) and four patients with type 2 diabetes mellitus (DM) were separated in seven subpopulations by Percoll density gradient centrifugation., Results: The proportion of old RBC was significantly higher in DM compared to HC. In both groups, in vivo aging was marked by changes in RBC shape and decreased cell volume. RBC nitrite, as marker for NO, was higher in DM and increased in both HC and DM during aging. RBC deformability was lower in DM and significantly decreased in old compared to young RBC in both HC and DM. RBC-NOS Serine1177 phosphorylation, indicating enzyme activation, increased during aging in both HC and DM. Arginase I activity remained unchanged during aging in HC. In DM, arginase I activity was significantly higher in young RBC compared to HC but decreased during aging. In HC, concentration of L-arginine, the substrate of RBC-NOS and arginase I, significantly dropped from young to old RBC. In DM, L-arginine concentration was significantly higher in young RBC compared to HC and significantly decreased during aging. In blood from healthy subjects, RBC-NOS activation was additionally inhibited by N5-(1-iminoethyl)-L-Ornithine dihydrochloride which decreased RBC nitrite, and impaired RBC deformability of all but the oldest RBC subpopulation., Conclusion: This study first-time showed highest RBC-NOS activation and NO production in old RBC, possibly to counteract the negative impact of cell shrinkage on RBC deformability. This was even more pronounced in DM. It is further suggested that highly produced NO only insufficiently affects cell function of old RBC maybe because of isolated RBC-NOS in old RBC thus decreasing NO bioavailability. Thus, increasing NO availability may improve RBC function and may extend cell life span in old RBC.

Puerarin possesses a wide spectrum of biological activities including ameliorating effects on blood stasis, but the definite mechanism of this effect is still not known. In this study, a (1)H NMR-based plasma and urinary metabonomic approach was applied to comprehensively and holistically investigate the therapeutic effects of puerarin on blood stasis and its underlying mechanisms. Puerarin was injected intraperitoneally once daily for consecutive 7 days. The blood stasis rat model was established by placing the rats in ice-cold water during the time interval between two injections of adrenaline. With pattern recognition analysis, a clear separation of blood stasis model group and healthy control group was achieved and puerarin pretreatment group was located much closer to the control group than the model group, which was consistent with results of hemorheology studies. 15 and 10 potential biomarkers associated with blood stasis in plasma and urine, respectively, which were mainly involved in energy metabolism, lipid and membrane metabolisms, amino acid metabolism and gut microbiota metabolism, were identified. Puerarin could prevent blood stasis through partially regulating the disturbed metabolic pathways. This work highlights that metabonomics is a valuable tool for studying the essence of blood stasis as well as evaluating the efficacy of the corresponding drug treatment., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Plasma expanders are commonly used in the management of critically ill patients, which may exhibit altered hemorheology. We evaluated the effects of various synthetic colloids and Lactated Ringer's (LR) solution on hemorheological parameters in vitro and in a rodent hemorrhagic shock model., Methods: For the in vitro experiments, rat blood was incubated with hydroxyethyl starch (HES) 130/0.4, HES 200/0.5, succinylated gelatine (GEL), or LR at various ratios. The control consisted of blood without dilution. The hemorheological parameters were measured after a 15-min incubation. For the in vivo study, rats were subjected to a severe volume-controlled hemorrhage and were resuscitated using a colloid solution (HES 130/0.4, HES 200/0.5, or GEL) or LR. The hemorheological parameters were measured 2 h after resuscitation., Results: The GEL significantly elevated the plasma viscosity compared to the other groups. In the in vitro study, GEL and LR accelerated the erythrocyte aggregation. There was no significant difference between HES 130/0.4, HES 200/0.5, and control groups regarding the aggregation amplitude and index. In the in vivo study, the aggregation amplitude increased significantly in the GEL group compared to the HES 130/0.4, HES 200/0.5, LR, and sham groups. There was no significant difference between the groups with respect to the elongation index in vivo., Conclusions: Hydroxyethyl starch did not change the erythrocyte aggregation compared to the control. GEL significantly accelerates the erythrocyte aggregation and elevates the plasma viscosity compared to hydroxyethyl starch. The in vitro hemorheological measurements most likely provide hints for the in vivo study.

Background: Elevated blood viscosity is a risk factor for atherosclerosis, thrombosis and other cardiovascular events. Our previous studies have suggested that consumption of Yerba mate tea (Ilex paraguariensis) has strong antioxidant and lipid-lowering properties in animals. The in vivo effects of Yerba mate on blood viscosity in humans, however, have not been studied., Objective: This study aims to investigate the effect of Yerba mate tea on the reduction of blood viscosity and the improvement of microcirculatory parameters commonly regarded as risk factors for serious cardio and cerebrovascular disorders., Methods: 142 subjects with high blood viscosity were recruited in this randomized, double-blind, placebo-controlled study. Yerba mate tea or placebo (5 g/day) was administered to different groups for 6 weeks. After treatment, results of hemorheological indexes, nailfold microcirculation, 6-keto-PGF1α and TXB2 and lipid profiles of subjects in the Yerba mate tea group were compared with those in the placebo-receiving group., Results: Parameters of blood viscosity and microcirculation were improved in the subjects from the Yerba mate tea group but not in placebo-receiving patients. After treatment, whole blood viscosity, plasma viscosity and the Equation K value of erythrocyte sedimentation rate (ESRK) decreased significantly in the Yerba mate group. Meanwhile, shape, flow state and nailfold microcirculation appeared positively changed. Specifically, blood flow speeds accelerated gradually and nailfold weighted integral values decreased significantly. Moreover, the vasodilator 6-keto PGF1α increased while the thromboxane TXB2 decreased in serum samples of subjects in the Yerba mate-receiving group. Overall, Yerba mate tea-receiving subjects saw nearly all measured values improve to levels comparable to those characteristic of patients with normal microcirculation., Conclusions: These results indicate the therapeutic capacity of Yerba mate tea in the treatment of high blood viscosity. Here, Yerba mate tea played a role in the regulation of various indexes of hemorheology, nailfold microcirculation, and the platelet aggregating factors 6-keto-PGF1a and TXB2. The regulation of these might be correlated with reduced blood viscosity and accelerating blood flow. Thus, Yerba mate tea may reduce some key risk-factors of cardiovascular disease. Daily consumption of Yerba mate tea may be a better-tolerated option for individuals with high blood viscosity and microcirculatory disturbance and as such, a novel preventative strategy for patients at-risk for vascular disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of vascular bradykinin on pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis (SAP)., Materials and Methods: Ninety male Wistar rats were randomly divided into a blank control group, an SAP group and a vascular bradykinin treatment group. The SAP model was induced by the retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The vascular bradykinin treatment group underwent gastrostomy, with a fine plastic tube placed in the stomach that led out of body through the abdominal wall.Vascular bradykinin was fully dissolved and administered at a dose of 20 U/kg once every 8 h. The pancreatic microcirculatory blood flow volume and velocity, microvascular permeability, hemorheology were evaluated respectively by double-channel laser Doppler flowmetry, the Evans blue leakage test, a blood rheology test instrument., Results: The pancreatic microcirculatory blood flow volume and velocity in the vascular bradykinin treatment group increased gradually after 48 h compared with the SAP group, and the changes were significantly different (p < 0.05). The pancreatic microvascular permeability of the vascular bradykinin treatment group was significantly reduced after 48 h compared with the SAP group (p < 0.05). The low shear rate blood viscosity, hematocrit and erythrocyte aggregation index of the vascular bradykinin treatment group were significantly decreased after 48 h compared with the SAP group (p < 0.05)., Conclusions: Vascular bradykinin can improve pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis.