Microchannel Array Flow Analyzer Research Articles

1106-P: Effects of Long-Term Dapagliflozin Treatment on Hemorheology (D-PATH Study)

Introduction: Hemorheology (blood viscosity) was reported to be a strong predictor of cardiovascular events in the Edinburgh Artery Study. However, deterioration in hemorheology through microvessels is a potential adverse effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. This study aimed to clarify the effect of dapagliflozin on blood fluidity. Method: This multi-center, open-label, randomized, comparative study included 90 patients with type 2 diabetes mellitu. Patients were randomly divided into treatment groups with and without dapagliflozin treatment, and each item was investigated. The primary endpoint was the whole blood transit time, based on the difference from the baseline to 16 weeks after enrollment, as measured by a microchannel array flow analyzer (MC-FAN). To assess this outcome, a 15% noninferiority margin (clinically significant cut-off value) was used. To test the noninferiority of the treatment, a t-distribution was used to calculate the 95% confidence interval to assess the difference from the baseline. Results: The whole blood transit time in the dapagliflozin group was 41.8 ± 6.1 sec (mean ± SD) before administration, and 43.4 ± 6.8 sec at 16 weeks after dapagliflozin administration. In the control group, the whole blood transit time was 40.5 ± 3.0 sec before administration and 39.9 ± 3.8 sec after 16 weeks. The difference between groups from the baseline to 16 weeks after enrollment was 1.7 sec [0.2, 3.5] (95% C.I), confirming the noninferiority of dapagliflozin administration. Futher, the analysis Results of the differences between groups according to the some items (the baseline of hematocrit, HbA1c levels and the whole blood transit time) for baseline, demonstrating the noninferiority of dapagliflozin administration in these items. Conclusion: Dapagliflozin was unlikely to have negative effects on blood fluidity after administration irrespective of the baseline Hematocrit, HbA1c levels and the whole blood transit time. Disclosure S. Ono: None. Y. Nakatani: None. A. Kawabe: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. Y. Aso: None. T. Yasu: None. Funding AstraZeneca

Clinical Significance of Low Blood Testosterone Concentration in Men as a Cardiovascular Risk Factor From the Perspective of Blood Rheology.

BackgroundRecent clinical studies have indicated the importance of low blood testosterone concentration or whole blood passage time (WBPT) which reflects blood rheology as a cardiovascular risk factor. On the contrary, there are no reports regarding the association of blood testosterone concentrations and WBPT. This cross-sectional study aimed to elucidate the clinical significance of low blood testosterone concentration in men as a cardiovascular risk factor from the perspective of blood rheology using WBPT.MethodsIn total, 382 male patients with traditional cardiovascular risk factor and no history of cardiovascular disease (age (mean ± standard deviation (SD)), 64 ± 10 years) were enrolled. Serum total testosterone concentration (T-T) was measured as a marker of testosterone level in vivo, and WBPT was also measured using microchannel array flow analyzer as a commercial device. The relationship between T-T and WBPT was evaluated.ResultsThere was a significantly negative correlation between T-T and WBPT (r = -0.45; P < 0.001). Furthermore, multiple regression analysis revealed that T-T (β = -0.25; P < 0.001) could be selected as an independent variable when WBPT was used as a subordinate factor. According to receiver operating characteristic curve analysis and the result of the previous report that determined WBPT of > 72.4 s as a risk for incidence of primary cardiovascular disease, T-T of < 551.4 ng/dL is the optimal cut-off point for discriminating high WBPT.ConclusionsThe study results showed that T-T is independently and inversely associated with WBPT in male patients with traditional cardiovascular risk factor and no history of cardiovascular disease. In addition, this study suggests that the incidence of primary cardiovascular events can be prevented by maintaining T-T at approximately ≥ 550 ng/dL from the perspective of blood rheology.

Usefulness of the Whole Blood Passage Time as a Predictor of Primary Cardiovascular Events in Patients With Traditional Cardiovascular Risk Factors.

BackgroundRecent clinical studies have reported that impaired hemorheology is a significant cardiovascular risk factor, but there has been no prospective study of its relationship with cardiovascular events. The aim of this prospective study was to assess the efficacy of whole blood passage time (WBPT), measured by a microchannel array flow analyzer (MC-FAN), as a predictor of primary cardiovascular events in patients with traditional cardiovascular risk factors.MethodsThe study enrolled 1,134 outpatients with traditional cardiovascular risk factors but no history of cardiovascular events (438 men and 696 women; mean ± standard deviation age, 67 ± 11 years). Based on the value of WBPT, the patients were assigned to one of three groups: L (low, WBPT < 50 s; n = 499), M (medium, WBPT 50 - 70 s; n = 295), or H (high, WBPT > 70 s; n = 340). The utility of the WBPT as a predictor of primary cardiovascular events was evaluated.ResultsDuring the follow-up period (median 81.9 months), major adverse cardiovascular events (MACE) occurred in 95 cases (L, 21 cases (4.2%); M, 24 cases (8.1%); H, 50 cases (14.7%); P < 0.001, log-rank test). In multivariate Cox regression analyses, the risk for MACE was significantly higher in group H than in group L (hazard ratio, 2.32; 95% confidence interval, 1.31 - 3.20; P < 0.01). A WBPT cut-off of 72.4 s yielded the largest area under the curve of 0.705 (95% confidence interval: 0.678 - 0.732), with a sensitivity of 51.7% and specificity of 85.4% for discriminating between those who did and did not experience MACE during the follow-up period.ConclusionThis study showed that WBPT evaluated by a MC-FAN was a predictor of primary cardiovascular events in patients with traditional cardiovascular risk factors.

Clinical Impact of Hemorheology on Subclinical Myocardial Injury in Patients with Hypertension.

BackgroundThe blood concentration of high-sensitivity cardiac troponin T (hs-cTnT) is a useful biomarker for myocardial injury or the pathogenesis of hypertension. Little is known about the relationship between hemorheology and myocardial injury in patients with hypertension. This cross-sectional study aimed to clarify the clinical impact of hemorheology on subclinical myocardial injury assessed with a microchannel array flow analyzer (MC-FAN) and its impact on hs-cTnT in patients with hypertension.MethodsA total of 447 outpatients (men: 181; women: 266; mean age: 65 ± 13 years), with no history of cardiovascular disease, including admission for heart failure, who were undergoing treatment for hypertension, were enrolled. Whole blood passage time (WBPT) as a marker of hemorheology was measured with a MC-FAN, and the relationship between hs-cTnT levels and various clinical parameters, including WBPT, was examined.Resultshs-cTnT levels were detected in 400 patients (89.5%). WBPT was significantly higher in patients with detectable hs-cTnT levels than in those with undetectable hs-cTnT levels (60.5 ± 16.8 s versus 50.2 ± 14.2 s, P < 0.001). In patients with detectable hs-cTnT levels, there was a significant positive correlation between WBPT and hs-cTnT level (r = 0.33; P < 0.001). Multiple regression analysis revealed that WBPT was an independent variable when hs-cTnT was a subordinate factor (β = 0.15; P < 0.01). Receiver-operating characteristic curve analysis indicated that a cutoff value for WBPT of 55.6 s yielded the largest area under the curve (0.744; P < 0.001) for discriminating high hs-cTnT levels as ≥ 0.014 ng/mL.ConclusionThe results indicate that WBPT is independently associated with hs-cTnT in hypertensive patients with no history of cardiovascular events, suggesting that impairment of hemorheology in small cardiac vessels causes subclinical myocardial injury. In addition, the study suggests that progression of myocardial injury can be prevented by maintaining WBPT at approximately ≤ 55 s.

Clinical Impact of Hemorheology Assessed Using the Microchannel Array Flow Analyzer on Renal Resistive Index in Patients With Type 2 Diabetes Mellitus

Background: The renal resistive index (RRI) assessed using ultrasonography is reportedly associated with not only kidney function but also cardiovascular disease incidence. In contrast, hemorheology assessed using the microchannel array flow analyzer (MC-FAN) has demonstrated the significance of cardiovascular risk factors in recent clinical studies. This cross-sectional study aimed to clarify the clinical impact of hemorheology assessed using MC-FAN on RRI in patients with type 2 diabetes mellitus from the perspective of primary prevention of cardiovascular events. Methods: In total, 302 outpatients undergoing treatment for type 2 diabetes mellitus (121 males and 181 females; mean age ± standard deviation, 66 ± 12 years) with no history of cardiovascular diseases were enrolled. The whole blood passage time (WBPT) was assessed using MC-FAN as a marker of hemorheology, and the relationship between RRI and various clinical parameters including WBPT was examined. Results: A significant positive correlation was observed between WBPT and RRI (correlation coefficient = 0.48; P < 0.001). Furthermore, the multiple regression analysis demonstrated that WBPT was selected as an independent variable for RRI as a subordinate factor (? = 0.37; P < 0.001). Patients with high WBPT (? 70 s) and median WBPT (50.2 - 69.6 s) had a significantly higher risk (odds ratio (OR): 7.9; 95% confidence interval (CI): 2.4 - 19.6; P < 0.01 and OR: 2.1; 95% CI: 1.1 - 7.8; P < 0.05, respectively) of having a high RRI (? 0.70) than those with low WBPT (? 50.0 s). Conclusions: The results of this study indicate that hemorheology assessed using MC-FAN is an important determining factor for RRI in patients with type 2 diabetes mellitus. Furthermore, we suggest that an increase in RRI can be prevented by maintaining WBPT ? 50.0 s. Further investigation of a large number of prospective studies, including intervention therapies, will be required to confirm the results of this study. J Endocrinol Metab. 2017;7(5):146-152 doi: https://doi.org/10.14740/jem448w

Relationship between cardiovascular risk factors and hemorheology assessed by microchannel method in patients with type 2 diabetes mellitus.

In addition to atherosclerosis, impairment of blood rheology is an important factor in cardiovascular events. The present study attempted to clarify the relationship between hemorheology and cardiovascular risk factors in patients with type 2 diabetes mellitus assessed by a microchannel method. We enrolled 294 patients with type 2 diabetes mellitus (109 males and 185 females; mean age, 69±11years) with no history of cardiovascular events. Hemorheology was evaluated with a microchannel array flow analyzer, and the relationship between whole-blood passage time (WBPT) and various clinical parameters was examined. WBPT was significantly correlated with advanced glycation end-product (AGE) levels at the skin (r=0.49, p<0.001), serum reactive oxygen metabolite concentrations (oxidative stress markers) (r=0.25, p<0.001), the cardio-ankle vascular index (CAVI, arterial function marker) (r=0.32, p<0.001), and a number of classical cardiovascular risk factors in an individual (r=0.45, p<0.001). Multiple regression analysis revealed that these factors were selected as independent variables for WBPT as a subordinate factor. Hemorheology is significantly associated with novel cardiovascular risk factors, such as AGEs, in vivo oxidative stress, and CAVI, and clustering of classical cardiovascular risk factors in patients with type 2 diabetes mellitus.

THE IMPACT OF GREEN TEA ON BLOOD FLUIDITY IMPROVEMENT AND WEIGHT LOSS

Introduction: Various studies have shown the benefi cial effects of green tea, not only on cardiovascular diseases but also on type 2 diabetes.Methods: In this study, the preparation of green tea water extract has been standardized to (-)-epigalocatechin gallate (EGCG), the major component of green tea. The role of green tea water extract on blood fl uidity and diabetes diseases has been studied in 13 Fructose-Fed Rat (FFR). The rats were given high fructose diet ad libitum for one week and then combination with green tea water extract every day for 6 days.Results: The results show, green tea water extract can reduces 100 μL blood passage times of wistar rat signifi cantly (p&lt;0.01) by Micro-Channel Array Flow Analyzer (MC-FAN) instrument. Green tea water extract also had strong effect in reducing abdominal fat (p&lt;0.05), blood glucose level (p&lt;0.01) and body weight (p&lt;0.01).Conclusion: These results suggest that green tea water extract may has benefi cial effects for the treatment of diabetes and reduce blood viscosity.

Relationship Between Hemorheology Assessed Using Microchannel Array Flow Analyzer and Kidney Function in Hypertensive Patients.

BackgroundKidney function is known to be closely associated with the pathogenesis of hypertension. In contrast, hemorheology assessed using microchannel array flow analyzer (MC-FAN) has demonstrated the significance of cardiovascular risk factors in recent clinical studies. The present cross-sectional study aimed to clarify the relationship between hemorheology assessed by MC-FAN and kidney function in hypertensive patients from the perspective of primary prevention of cardiovascular events.MethodsIn total, 453 outpatients undergoing treatment for hypertension (176 men and 277 women; mean age ± standard deviation: 65 ± 13 years) with no history of cardiovascular disease were enrolled. Whole blood passage time (WBPT) was measured using MC-FAN as a marker of hemorheology, and the relationships with various clinical parameters including kidney function were examined.ResultsA significant correlation was observed between WBPT and the parameters of kidney function such as estimated glomerular filtration rate (r = -0.14, P < 0.01), urinary albumin excretion (r = 0.40, P < 0.001), and renal resistive index (r = 0.44, P < 0.001). Furthermore, multivariate analysis demonstrated urinary albumin excretion, renal resistive index, skin autofluorescence, derivatives of reactive oxygen metabolites, and hematocrit as independent variables for WBPT as a subordinate factor.ConclusionsThe results of the present study indicate that hemorheology assessed by the MC-FAN is significantly associated with markers of kidney function, such as albuminuria and increased renovascular resistance, in hypertensive patients.

Clinical Impact of Hemorheology Assessed Using the Microchannel Array Flow Analyzer on Renal Resistive Index in Patients With Type 2 Diabetes Mellitus

Background: The renal resistive index (RRI) assessed using ultrasonography is reportedly associated with not only kidney function but also cardiovascular disease incidence. In contrast, hemorheology assessed using the microchannel array flow analyzer (MC-FAN) has demonstrated the significance of cardiovascular risk factors in recent clinical studies. This cross-sectional study aimed to clarify the clinical impact of hemorheology assessed using MC-FAN on RRI in patients with type 2 diabetes mellitus from the perspective of primary prevention of cardiovascular events. Methods: In total, 302 outpatients undergoing treatment for type 2 diabetes mellitus (121 males and 181 females; mean age ± standard deviation, 66 ± 12 years) with no history of cardiovascular diseases were enrolled. The whole blood passage time (WBPT) was assessed using MC-FAN as a marker of hemorheology, and the relationship between RRI and various clinical parameters including WBPT was examined. Results: A significant positive correlation was observed between WBPT and RRI (correlation coefficient = 0.48; P &lt; 0.001). Furthermore, the multiple regression analysis demonstrated that WBPT was selected as an independent variable for RRI as a subordinate factor (beta = 0.37; P &lt; 0.001). Patients with high WBPT (&gt;= 70 s) and median WBPT (50.2 - 69.6 s) had a significantly higher risk (odds ratio (OR): 7.9; 95% confidence interval (CI): 2.4 - 19.6; P &lt; 0.01 and OR: 2.1; 95% CI: 1.1 - 7.8; P &lt; 0.05, respectively) of having a high RRI (&gt;= 0.70) than those with low WBPT (&lt;= 50.0 s). Conclusions: The results of this study indicate that hemorheology assessed using MC-FAN is an important determining factor for RRI in patients with type 2 diabetes mellitus. Furthermore, we suggest that an increase in RRI can be prevented by maintaining WBPT &lt;= 50.0 s. Further investigation of a large number of prospective studies, including intervention therapies, will be required to confirm the results of this study. J Endocrinol Metab. 2017;7(5):146-152 doi: https://doi.org/10.14740/jem448w

Association of Hemorheology With High-Sensitivity Cardiac Troponin T Levels in Patients With Type 2 Diabetes Mellitus Assessed by Microchannel Array Flow Analyzer.

BackgroundRecent studies on high-sensitivity cardiac troponin T (hs-cTnT) and whole blood passage time (WBPT), estimated by hemorheology assessed with the microchannel array flow analyzer (MC-FAN), have revealed the significance of cardiovascular risk factors. However, there are no known reports on the relationship between these two clinical parameters. This cross-sectional study aimed to clarify the associations between WBPT and hs-cTnT levels in patients with type 2 diabetes mellitus from the perspective of subclinical myocardial injury or the primary prevention of cardiovascular events.MethodsA total of 301 outpatients (men, 116; women, 185; mean age, 65 ± 11 years), with no history of cardiovascular diseases, undergoing treatment for diabetes mellitus were enrolled. Hs-cTnT levels and WBPT were measured using a commercial device, and the relationship between hs-cTnT levels and various clinical parameters, including WBPT, was examined.ResultsHs-cTnT levels were detected in 261 (86.7%) patients. WBPT was significantly higher in patients with detectable hs-cTnT levels than in those with undetectable hs-cTnT levels (64 ± 18 s vs. 51 ± 13 s, P < 0.001). In patients with detectable hs-cTnT levels, there was a significantly positive correlation between WBPT and hs-cTnT levels (r = 0.40; P < 0.001). Furthermore, multiple regression analysis revealed that WBPT (β = 0.24; P < 0.001) was an independent variable when hs-cTnT was a subordinate factor. Conversely, patients with high (≥ 70 s; odds ratio, 5.3 (95% CI, 1.6 - 16.1); P < 0.01) and median (50.2 - 69.8 s; odds ratio, 3.8 (95% CI, 1.2 - 12.4); P < 0.05) WBPT had a significantly higher risk for high hs-cTnT levels (≥ 0.014 ng/mL) than those with low WBPT (≤ 50.0 s).ConclusionsThe results of this study indicated independent associations of hemorheology with hs-cTnT in patients with type 2 diabetes mellitus assessed by MC-FAN. We suggest that an increase in hs-cTnT levels can be prevented by maintaining WBPT at ≤ 50.0 s.

Rivaroxaban attenuates leukocyte adhesion in the microvasculature and thrombus formation in an experimental mouse model of type 2 diabetes mellitus

Thrombosis is a major complication in diabetes mellitus. Since Factor Xa inhibitors are not only inhibit the coagulation system but also attenuate the leukocyte-endothelial interaction in acute inflammation models, the purpose of this study is to confirm the similar effects of rivaroxaban in a mouse model of type 2 diabetes mellitus. In the treatment groups, either 5 or 10mg/kg of rivaroxaban dissolved in DMSO was orally given to KK-A(y) mice for 7 weeks (n=6 in each group). KK-A(y) mice fed by chow containing DMSO without rivaroxaban for 7 weeks were served for the control group (n=6). Following clamping of the mesenteric vein for 20 minutes, intravital microscopic observation of the intestinal microcirculation and the measurement of bleeding time after the needle puncture were carried-out. In another series, the calculation for blood cell counts and the measurement of blood fluidity using micro channel array flow analyzer (MC-FAN) were performed. The initial event in the microvasculature is the leukocyte adhesion on endothelium. Then, the leukocytes make clusters and the platelets are involved in. These leukocyte-platelet conjugates aggregate and form thrombus. The leukocyte adherence and the microthrombus formation was significantly suppressed with the treatment of 10 mg/kg of rivaroxaban compared to the control group (P<0.05). While, the bleeding time was significantly extended with the treatment with 10mg/kg of rivaroxaban (P<0.01). The blood fluidity was maintained best with the treatment of 10 mg/kg rivaroxaban. Rivaroxaban attenuates the leukocyte-platelet-endothelial interaction, which leads to the attenuation of microthrombus formation in a mouse model of diabetes mellitus.

Factors affecting impairment of blood rheology in obese subjects

ObjectivesImpairment of blood rheology has been reported to be associated with cardiovascular diseases. Recently, visible micro channel methods [micro channel array flow analyzer (MC-FAN)] have been developed to clinically evaluate blood rheology. The aim of this cross-sectional study is to clarify the factors important for impairment of blood rheology in obese subjects using MC-FAN. MethodsOne hundred and fifty-nine obese subjects and 100 non-obese subjects with no history of cardiovascular diseases were enrolled. Blood passage time (BPT) was measured using MC-FAN and relationships between BPT and various clinical parameters were examined. ResultsBPT was significantly higher in obese subjects than in non-obese subjects (obesity vs. non-obesity: 62.8±17.9s vs. 54.1±14.6s, p<0.001); however, there were no significant relationships between BPT and body mass index or waist circumference in obese subjects. BPT was significantly related to systolic blood pressure levels (r=0.21; p<0.001), high-sensitivity C-reactive protein concentrations (r=0.37; p<0.001), a marker of inflammation, and derivatives of reactive oxygen metabolites test (r=0.38; p<0.001), a marker of oxidative stress, smoking, and exercise habits in obese subjects. Furthermore, multivariate analysis revealed that derivatives of reactive oxygen metabolites test (t=5.2; p<0.001), high sensitivity C-reactive protein concentration (t=3.6; p<0.01), smoking (t=3.2; p<0.001), and exercise habits (t=−2.4; p<0.05) were independent variables for BPT. ConclusionData indicate that inflammation, oxidative stress, and lifestyle choices are more important factors for impairment of blood rheology, which is evaluated by MC-FAN, than the degree of adiposity in obese subjects.

Blood Fluidity Enhancement by Electrical Acupuncture Stimulation is Related to an Adrenergic Mechanism

We have reported that electrical acupuncture stimulation (ACU) increases blood fluidity by decreasing platelet aggregation. In this study, we investigated the mechanism causing the increase of blood fluidity. The effects of ACU on blood fluidity and platelet adhesion were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20).Male Wistar rats (7–8 weeks old) were used in the study. ACU (1 or 100Hz, 3–5V), which causes slight muscle twitching, was applied to the ZuSanli (ST-36) acupoint for 15 or 60 minutes once/day. Blood samples were collected from the inferior vena cava.ACU applied to ST-36 revealed significant increases in blood fluidity, while platelet adhesion activity decreased, regardless of the difference of stimulus time. The acupuncture had an immediate effect. Even if naloxone was administered during acupuncture stimulus, the blood flow time shortened in a similar way, as in the only acupuncture stimulus group. In addition, the effect of acupuncture on blood fluidity was inhibited by a β-antagonist. The results indicate that ACU affects blood fluidity depending on the acupoints, and that the effect of ACU might involve an endogenous adrenergic mechanism.

Thrombogenic potential of whole blood is higher in patients with acute coronary syndrome than in patients with stable coronary diseases

Introduction Although thrombogenic potential of blood may play an important role for the onset of acute coronary syndrome (ACS), there is no established way to evaluate it by single parameter. We compared the thrombogenic potential of whole blood between patients with ACS and those with stable coronary diseases using single comprehensive parameter. Materials and Methods Consecutive patients with ACS (n = 146) and those with stable coronary heart diseases (control, n = 92) were prospectively examined. Thrombogenic potential of whole blood was evaluated by blood vulnerability index measured by Micro-Channel Array Flow Analyzer (MC-FAN). Results Blood vulnerability index was higher in ACS than in control patients (5099 ± 2278 vs. 2071 ± 389, p < 0.0001), higher in acute MI than in unstable angina patients (5693 ± 2146 vs. 3524 ± 1841, p < 0.0001), and higher in ACS patients with initial TIMI 0/1 flow grade than in those with TIMI 2/3 flow grade (6061 ± 1936 vs. 2560 ± 1301, p < 0.0001). Furthermore, blood vulnerability index decreased from acute to chronic stage in acute MI patients. Multivariate logistic regression analysis revealed that high blood vulnerability index, high LDL cholesterol, high CRP, no use of aspirin, and no use of β-blocker were the independent contributors for the onset of ACS. Conclusion High thrombogenic potential of whole blood evaluated by blood vulnerability index was significantly associated with ACS and was reduced from acute to chronic stage in acute MI. Condensed Abstract Thrombogenic potential of whole blood was evaluated by blood vulnerability index measured comprehensively by Micro-Channel Array Flow Analyzer (MC-FAN) in consecutive patients with ACS (n = 146) or stable coronary diseases (control, n = 92) prospectively. Blood vulnerability index was significantly higher in ACS patients, especially in acute MI and poor initial TIMI flow grade patients, compared with control patients; and blood vulnerability index was reduced from acute to chronic stage in acute MI patients.

The Effect of lecithin extracted from Japanese anchovy (Engraulis japonicas) on Blood Passage and Serum Lipid Profile in Rats

To investigate the effects of lecithin extracted from Japanese anchovy on blood passage and serum lipid profile were assessed in vivo. Sprague Dawley strain rats were divided into five groups of ten rats each; normal control, negative control and three dosages of lecithin treated groups (80, 200 and 500 mg/kg). Serum total cholesterol, triglyceride, LDL‐cholesterol, atherogenic index (AI) and cardiac risk factor (CRF) contents were significantly reduced in the lecithin treated groups compared to the negative control group (P&lt;0.05). The level of serum serotonin in the lecithin treated groups was significantly reduced compared to the negative control group (P&lt;0.05). The platelet aggregation was inhibited in lecithin treated groups. There was no significant difference compared to the negative control group. Blood passage time of the lecithin treated group showed a tendency to decrease compared to the negative control group, which was studied with micro channel array flow analyzer (MC‐FAN). Also, in the histopathological assay of aorta wall lumen, the cholesterol aggregation level in the lecithin treated groups was reduced compared to the negative control group. All these results suggest that Japanese anchovy‐extracted lecithin might have anti‐atherogenic effect via lipid profile improvement.

Optically Patternable Polymer Films as Model Interfaces to Study Cellular Behaviour on Topographically Structured Materials

We assessed blood interaction with different micrometer-scale topographies under flow conditions using a micro-fluidic array system. The channels of the micro-fluidic array chip were coated with azobenzene polymer films, which were then topographically structured using a one-step non-contact optical technique. A set of surfaces with different topographies was produced varying laser irradiation duration. These surfaces were then exposed to blood flow. The blood flow rate was measured with a micro-channel array flow analyzer. The measured blood flow rates decreased with time for all the samples, indicating formation of platelet clots which obstruct the channels during flow. This effect appeared enhanced on polymer surfaces having a sinusoidal profile with 200-nm-high ridges and 1.2-μm-grating spacing. The morphology of platelets that adhered on the polymer films was studied by scanning electron microscopy. Platelets adhered on azobenzene surfaces with flat topographies, typically exhibiting filopodia. Platelets adhered on optically structured surfaces also exhibited lamellipodia and appeared flattened on surfaces with the highest ridges. We conclude that surface topography influences blood behaviour on azobenzene polymer films.

An in vitro method for screening anti-platelet agents using a microchannel array flow analyzer

New in vitro methods are desirable for the analysis of platelet aggregation and screening novel anti-platelet agents using whole blood. To this end, we examined platelet aggregation and thrombus formation in whole human blood from healthy volunteers using a microchannel array flow analyzer (MC-FAN). Platelet aggregation in whole blood, treated with the activating agents ADP, collagen or ristocetin was detected in the MC-FAN by measuring the decrease in flow rate as a function of agent concentration. The results were compared with aggregation in platelet rich plasma (PRP) in a conventional aggregometer, as measured by the increase in optical density. The MC-FAN detected platelet aggregation in whole blood at two- to four-fold lower concentrations of agonist compared to those in PRP in the aggregometer. Anti-platelet agents attenuated the decrease in blood flow rate in the MC-FAN by inhibiting fibrin formation and platelet aggregation, but anticoagulants only inhibited fibrin formation and did not affect blood flow rates. These findings suggest that the MC-FAN system may be a useful method for the evaluation of platelet activation and facilitate the development of novel anti-platelet agents.

The Influence of Metabolic Syndrome and Chronic Kidney Disease on Hemorheology Assessed by the Microchannel Method

Metabolic syndrome (MetS) and chronic kidney disease (CKD) are individual risk factors for cardiovascular disease (CVD). Abnormal hemorheology may be associated with CVD in both disorders. The present study investigated the impact of MetS and CKD on hemorheology. We studied 138 adults (women/men=63/75, mean age=52.2 years), who included 87 participants with MetS and 33 with CKD. The hemorheology was assessed by the index of 'whole blood passage time (WBPT)' using the Micro Channel array Flow ANalyzer (MC-FAN). The WBPT values of MetS participants were significantly higher than those of non-MetS participants (52.5±13.1 vs. 46.3±7.7 sec, p=0.03). The WBPT values of CKD participants were significantly higher than those of non- CKD (55.5±12.7 vs. 48.6±11.0 sec, p=0.003). The significant influence of MetS and CKD on WBPT was qualified by their effect modification to WBPT (p=0.04). There was a significantly greater influence of the combination of MetS and CKD on WBPT (59.9±13.4 sec) in comparison to the influence of non-MetS and CKD (46.6±3.5) or non-CKD and MetS (50.0±12.2). The influence of the combination of MetS and CKD was clearer in men, relative to women. Abnormal hemorheology as assessed using MC-FAN may be enhanced by the combination of MetS and CKD.

Effects of Unripe Citrus hassaku Fruits Extract and Its Flavanone Glycosides on Blood Fluidity

The enhancement of blood fluidity may lead to improvements in skin problems resulting from unsmooth circulation or blood stagnation. Since a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits may be a useful ingredient in skin-whitening cosmetics, the present study was designed to examine the effect of CH-ext on blood fluidity. CH-ext concentration-dependently inhibited in vitro collagen-induced rabbit platelet aggregation and in vitro polybrene-induced rat erythrocyte aggregation. The CH-ext showed in vitro fibrinolysis activity in fibrin plate assay. Activity-guided fractionation of the CH-ext using antiplatelet activity, inhibitory activity of erythrocyte aggregation, and fibrinolysis activity revealed that these activities of CH-ext were attributable to naringenin-7-glycoside (prunin). Successive oral administration of CH-ext to rats inhibited the lipopolysaccharide (LPS)-induced decrease of blood platelets and fibrinogen, and LPS-induced increase of fibrin degradation products (FDP) in LPS-induced disseminated intravascular coagulation (DIC) model rats. Effects of CH-ext on blood fluidity were analyzed by a micro channel array flow analyzer (MC-FAN). Preventive oral administration of CH-ext to rats showed dose-dependent reduction of the passage time of whole blood flow of the DIC model rats in comparison with that of the vehicle control rats. These results imply that CH-ext may have effects which improve effects on blood fluidity.

Determinants of Blood Rheology in Healthy Adults and Children Using the Microchannel Array Flow Analyzer

The reference values of blood rheology in healthy participants, especially children, are not available. The purpose of this study was to determine the blood passage time (BPT) as an index of blood rheology, in healthy children and adults, using the microchannel array flow analyzer, and to investigate the hematological factors that define BPT. Participants were 61 healthy children (35 boys, 26 girls; age 5-6 years) and 71 healthy adults (24 men, age 35.2 +/- 14.1 years; 47 women, age 44.7 +/- 14.1 years, mean +/- standard deviation [SD]). Blood passage time and various hematological variables (blood cell count, serum lipids, and fibrinogen) were measured and compared among the 4 study groups. Blood passage time values were significantly higher in adult men (48.8 +/- 5.8 seconds) than in boys (41.9 +/- 4.0 seconds), girls (43.7 +/- 7.8 seconds), and adult women (42.4 +/- 4.8 seconds). Stepwise regression analysis identified erythrocyte count and hemoglobin (Hb) as the significant and independent determinants of BPT (P < .05). Our study demonstrates that BPT is significantly longer in healthy adult men than in adult women and children, and that erythrocyte count and Hb are significant determinants of blood rheology.