Effects of L-arginine on impaired blood fluidity after high-intensity exercise: An in vitro evaluation.

BACKGROUND: Exercise-induced impairment of blood fluidity is considered to be associated with thrombosis development. However, the effects of L-arginine on blood fluidity after exercise remain unclear. OBJECTIVE: We investigated the mechanisms of impaired blood fluidity after high-intensity exercise, and examined whether L-arginine improves exercise-induced blood fluidity impairment in vitro. METHODS: Ten healthy male participants performed 15 minutes of ergometer exercise at 70% of their peak oxygen uptake levels. Blood samples were obtained before and after exercise. L-arginine and NG-monomethyl-L-arginine acetate (L-NMMA)-a nitric oxide (NO) synthase inhibitor-were added to the post-exercise blood samples. Using Kikuchi's microchannel method, we measured the blood passage time, percentage of obstructed microchannels, and the number of adherent white blood cells (WBCs) on the microchannel terrace. RESULTS: Exercise increased the hematocrit levels. The blood passage times, percentage of obstructed microchannels, and the number of adherent WBCs on the microchannel terrace increased after exercise; however, they decreased in a dose-dependent manner after the addition of L-arginine. L-NMMA inhibited the L-arginine-induced decrease in blood passage time. CONCLUSIONS: High-intensity exercise impairs blood fluidity by inducing hemoconcentration along with increasing platelet aggregation and WBC adhesion. The L-arginine-NO pathway improves blood fluidity impairment after high-intensity exercise in vitro.

Near-Newtonian Blood Behavior - Is It Good to Be a Camel?

From a certain level of exercise-intensity onward, hematocrit increases in horses, which brings more oxygen carriers into the bloodstream. Camels, however, when used in competitive racing could be even in need of iron supplementation and blood transfusions due to a severe reduction of their available hematocrit compared to their resting hematocrit. Since the extrinsic and intrinsic mechanical properties of camel erythrocytes (RBC) are so different compared to RBCs of other mammals, the question arises whether this observation might be a response to endurance exercise aiming at keeping the RBC count low. Rheometry indicated dromedary camel blood to behave almost Newtonian, which is unique amongst mammals. Shear thinning did increase with the hematocrit, but remained marginal compared to horses. As a result, camel whole blood viscosity (WBV) exceeded horse WBV at high shear rates, an effect, which was significantly augmented when the packed cell volume (PCV) was increased. Therefore, in camels any infusion of RBCs into the bloodstream can increase the cardiac work and the energy input into the endothelium more effectively, which should generate vascular remodeling in the long term. Yielding, however, was completely absent in camel blood, confirming low cohesion between its components at quasi-static flow. Camel blood remained a viscous liquid without a threshold even at unphysiologically high PCVs. This can help to washout lactate when camels start to dehydrate and might contribute to the sustained working ability of these animals. The subtle pseudoplastic behavior and the high viscosity contrast across the RBC membrane point to weak coupling between blood flow and red cell behavior. We predict that RBCs flow as separate entities and can show various types of motion, which can lead to friction instead of being collectively aligned to the flow direction. In comparison to horses, this behavior will become relevant at higher RBC counts in front of flow obstacles and possibly cause vascular remodeling if the PCV rises during strenuous exercise, a matter that should be avoided.

Fetal growth retardation and hemorheological predictors of oxygen delivery in hypertensive vs normotensive pregnant women.

Physiological modifications of blood rheology during pregnancy and their alterations in pregnant hypertensive women have been extensively studied in the 1980's. Since vascular resistance is higher in hypertensive pregnant women whose newborns are small-for gestational-age (SGA), we investigated in a personal database if growth retardation of newborns is related to the oxygen delivery index (ratio hematocrit/blood viscosity) and to the difference between hematocrit (Hct) and the prediction of its optimal valued based on Quemada's equation. A sample of 38 hypertensive pregnant women (age 29 yr±1) was compared with 64 controls matched for age and gestational age, studied at 35±1 weeks gestation, extracted from a larger series of 162 pregnant women. On the whole the hypertensive group gave birth to smaller children (p = 0.014). Plasma viscosity correlated with blood pressure (BP) only in hypertensive women (r = 0.403 p < 0.05). The bell-shaped curve of predicted optimal Hct of non hypertensive pregnant women was similar to that of non-pregnant women, but in hypertensive women it was shifted toward higher values (p = 0.07), and the predicted optimal Hct (but not the actual one) was correlated with systolic blood pressure (SBP) (r = 0.349 p < 0.001) and diastolic blood pressure (DBP) (r = 0.218 p < 0.05). The predicted optimal Hct/viscosity (h/η) ratio was higher in hypertensive women whose newborns exhibited a low birth weight (p = 0.03), resulting in a higher discrepancy between actual and model-predicted «ideal¼ values of h/η ratio (p = 0.03) and Hct (p = 0.02) compared with the subgroup with no growth retardation. Therefore, in hypertensive women whose newborns exhibited a low birth weight, hemorheological parameters predicting oxygen supply are shifted to lower values than predicted by the model.

Effect of diet on blood viscosity in healthy humans: a systematic review.

BACKGROUND: Increased whole blood viscosity is associated with increased risk of morbidity and mortality of several life-threatening diseases, including cardiovascular and cerebrovascular disease. The effect of diet on human health has been indicated in many studies, and a health dietary pattern can reduce the incidence of several chronic diseases. OBJECTIVE: The aim of this systematic review was to assess the effect of diet on blood viscosity and related parameters such as haematocrit (HCT). METHODS: This systematic review was carried out in 2017. MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to 2 May 2017. We selected and included randomized clinical trials (RCTs) in the study. The inclusion criteria were articles that describe the effect of any types of local and traditional diet on blood viscosity in apparently healthy individuals. RESULTS: Three randomized controlled trials were included in this systematic review. Different diets were used in the included trials. In one study, ingested dried-bonito broth (DBB) for four weeks, significantly reduced the blood passage time in the intervention group from 55.4±3.4 to 47.6±2.0 sec (mean ± SEM, p<0.05) compared with no significant change in the placebo group. Another study has shown significantly increased blood fluidity score in a vegetarian group in contrast to the control group after six weeks. In the last study, plasma viscosity was significantly decreased in a group which used onion-olive-oil capsules compared to the placebo group, with a highly significant difference between the two groups (p=0.0015). CONCLUSIONS: Our components of food diets may decrease blood viscosity in health status. Better and expanded methodology may improve our results.

The effect of exercise on blood fluidity: Use of the capillary model to assess the clogginess of blood.

AIM: The goal was to evaluate the effects of exercise on the clogginess of blood as well as the effect of increased blood cell count and hematocrit levels after exercise. We also investigated the mechanisms underlying the clogginess of blood. METHODS: The time required for blood to pass through microchannels was measured. We focused on assessing the consecutive passage times for serial 20 µL volumes. We used heparinized peripheral blood obtained from subjects after exercise conducted at three intensity levels. Blood samples were also adjusted to achieve specific hematocrit levels or supplemented by addition of adenosine diphosphate (ADP). RESULTS: The sequential blood passage times of consecutive 20 µL volumes increased with platelet aggregation and adhesion of white blood cells (WBC). We also observed an increase with blood cell counts and hematocrit levels. These changes occurred after high intensity exercise but not after low or medium intensity exercise. Furthermore, the sequential blood passage times of 20 µL volumes increased with platelet aggregation and adhesion of WBC at an ADP concentration at the threshold of aggregation but not at higher levels of hematocrit. CONCLUSIONS: These findings suggested that high intensity exercise might induce the clogginess of blood by enhanced platelet aggregation and adhesion of WBC.

Rheologic results and their correlation to hemostatic changes in patients with moderate and severe preeclampsia: an observational cross-sectional study.

Previous study have shown an association between failure of physiological hemodilution during 2nd trimester and an increased risk for the development of subsequent pregnancy complications such as early birth, birth of a growth retarded newborn (IUGR), low fetal birth weight and preeclampsia. The latter complication in particular goes along with dramatic changes in the placental perfusion as well as systemic maternal blood flow. Severity of preeclampsia may be preceded by distinct impaired hemodilution and reflected by the results of rheological parameters. A subgroup analysis was performed in a community based retrospective study of 4,985 consecutively recorded singleton pregnant women of whom 423 had preeclampsia. Mean 2nd trimester hemoglobin levels and blood rheological results at the time of delivery were assessed and compared in women with moderate and severe preeclampsia. Mean 2nd trimester hemoglobin levels were calculated from the maternal records. Rheological variables included plasma viscosity (KSPV 1 Fresenius) and Red blood cell aggregation in stasis and under low shear conditions (MA1-Aggregometer; Myrenne). According to the definition of the German Society of Gynecology and Obstetrics (DGGG) 314 women had moderate preeclampsia (74.2%), while 109 had severe preeclampsia due to the presence of a blood pressure>170/110 mmHg (n=41; 9.7%), and/or IUGR<5th percentile (n=28; 6.6%), and/or HELLP-Syndrome (n=10; 2.4%), and/or proteinuria≥5 g/24 h (n=30; 7.1%). Age, BMI, smoking, and maternal weight were comparable in the groups, while gestational age at delivery as well as fetal outcome parameter were statistically significant unfavourable in patients with severe preeclampsia. Mean 2nd trimester hemoglobin level were statistically significantly higher in women who developed severe vs. moderate preeclampsia (m=12.75±0.99 g/dL vs. m=12.50±1.05 g/dL; p=0.033). However, in the ROC calculations a hemoglobin value of 12.05 g/dL revealed best sensitivity (78%) and specificity (33.8%) in women with subsequent diagnosis of severe preeclampsia, whereas sensitivity was 100% for a value>10.95 g/dL. There were no statistically significant differences for none of the rheological parameters at the time of delivery between groups of patient with moderate v.s severe preeclampsia. Severe preeclampsia and IUGR, however, was associated with statistically significantly higher RBC aggregation as compared to patients with moderate preeclampsia. Plasma viscosity was statistically significantly (p<0.05) correlated with Fibrinogen values (r=0.16), leukocyte-(r=0.11) and platelets-count (r=0.127), and hemoglobin/hematocrit values in particular (r=0.23/0.26). Although mean 2nd trimester hemoglobin concentration are higher in patients with subsequent development of severe preeclampsia, due to the low sensitivity and specificity of this parameter clinical use for identifying women at risk is of limited value. On the other hand, a hemoglobin value below 11.0 g/dL excluded the risk for severe preeclampsia to 100%. Blood rheological parameters at the time of delivery in the absence of IUGR are not markedly influenced by severity of preeclampsia.

Changes in blood fluidity caused by electroacupuncture stimulation.

In Oriental medicine, the state of blood stagnation is called "Oketsu," meaning preceding state or symptomatic of sickness. Acupuncture stimulation is often used clinically for the treatment of "Oketsu." The degree of "Oketsu" is indicated by tongue color and form, swelling, paroxysmal blushing, and dark circles under the eyes. The blood's fluidity is generally thought to be a blood stagnation factor. "Oketsu" is now considered as physiological blood flow and is studied from the perspective of the blood's fluidity and vascular resistance. In our preliminary research, acupuncture stimuli were very effective in treating conditions associated with a decrease in the fluidity of the blood, such as "Oketsu." In this review, we discuss recent progress in acupuncture therapy and report mechanisms of its action; we then focus on our original findings on these topics. Furthermore, we propose new factors related to acupuncture stimuli, including the blood's fluidity, and report our investigations, using the restraint stress method, on the mechanisms underlying acupuncture stimuli.

Microcirculation in hypertensive patients.

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

Blood fluidity and "Oketsu; blood stagnation", effect of acupuncture and its mechanisms / 全日本鍼灸学会雑誌

In oriental medicine, the state in which blood is stagnant is called "oketsu, (Yu xie)"meaning preceding state or symptomatic of sickness. However, the pathological detail and mechanism of "oketsu"is not clear. Therefore we attempt to clarify the meaning of "oketsu"with Western medical knowledge and methods. The relationship between "oketsu"and blood fluidity (BF) was studied in human studies and the influence of several kinds of stress, "anti-oketsu"herbal medicine, electro-acupuncture stimulation (ACU), adrenoceptor agonist and antagonist on BF, platelet aggregation (PA), plasma ATP level, reactive oxygen metabolites level (d-ROM) and biological anti-oxidant potential level (BAP) were studied in animal studies using male Wistar rats. BF and PA were examined using a Micro Channel Array Flow Analyzer (MC-FAN) and a laser scattering platelet aggregometer (PA-20), respectively. D-ROM and BAP levels were studied using a Free Radical Elective Evaluator. In ACU study, 1Hz, 3-5 V stimulation was applied to the acupoints for 15 or 60 minutes. Stimulated acupoints were as follows:ZuSanli (ST-36), Sanyinjiao (SP-6), Hegu (L-I4), Neiguan (P-6) and Shenshu (BL-23). A significant decrease of BF was observed in "oketsu"patients compared to the "non-oketsu"patients in human studies. In the animal study, restrained and electrical shock stress applied to rats results in a quick decrease of BF, increase of PA, increase of plasma ATP level, increase of d-ROM level and decrease of BAP level. ACU applied to ST-36, SP-6 and L-14 revealed significant increases in BF, while PA activity decreased. The effect was observed even with 15 min stimulation. However, no significant changes were observed when ACU was applied to P-6 and BL-23. Furthermore, ACU applied to ST-36 represented a significant reduction to the stress induced blood changes such as BF, PA, plasma ATP level, d-ROM, and BAP level. These data suggest the close relation of BF with the "Oketsu"and that sympathetic nervous system activity and plasma ATP level have important roles in the changes of blood fluidity. Acupoints may have some role in the result that ACU affects BF depending on the stimulation loci. ACU has an immediate effect on BF since 15 min stimulation shows a significant effect. PA decrease by ACU suggests that an increase of BF is mainly associated with PA ability. The result that ACU reduced the stress induced BF and other changes of blood properties may imply that ACU has anti-stress activity.

Influence of Chinese Herbal Medicine on Reactive Oxygen and Blood Fluidity in Rats / 日本東洋医学雑誌

Swelling and pain appear when blood flow is delayed in states of “<i>oketsu</i>.” Until now “<i>oketsu</i>” as a circulatory disturbance has been studied from profiles of vascular resistance characteristics and blood fluidity. Blood fluidity is influenced by blood cell function, plasma ingredients and reactive oxygen. In this study, we administered the various Chinese herbal medicines, tokishakuyakusan, saikokaryukotsuboreito, tokakujokito, keishibukuryogan and juzentaihoto to determine the effect of these medicines on “<i>oketsu</i>” by observing reactive oxygen dynamics and blood fluidity in rats.SPF male Wistar rats weighing 200 g were used. Each experimental group was given feed containing 3% extract of one Chinese herbal medicine for1week. Blood samples were mixed with heparin, EDTA-2K or sodium citrate to block coagulation. Blood fluidity was measured with a Micro Channel Array Flow Analyzer (MC-FAN). A PA-20 examined platelet aggregation by the reaction to ADP, which activates platelet aggregation. Reactive oxygen dynamics were measured with a Free Radical Elective Evaluator (FREE).As a result, anti-oxidative ability and blood fluidity increased in all Chinese herbal medicine-administered groups. Furthermore, an inverse correlation between the fluidity of erythrocyte suspensions and anti-oxidative ability was shown. We speculate that an anti-oxidative influence of Chinese herbal medicines affected erythroid deformability or stickiness. In addition, tokishakuyakusan, tokakujokito and keishibukuryogan decreased platelet aggregation ability.This study shows that “<i>oketsu</i>” improves blood properties and suggests that Chinese herbal medicine improves decrease in blood fluidity, the causes of conditions such as thrombosis or embolism.

INFLUENCE OF EXERCISE ON BLOOD FLUIDITY IN RAT: INFLUENCE OF TRAINING IN HIGH TEMPERATURE ENVIRONMENTS ON ERYTHROCYTE IN RAT / 体力科学

[Objective] Perspiration is almost only heat radiation mechanism under high temperature environments. And sudoriferous water is supplied from blood. Blood flow is determined by blood fluidity, blood volume and the cardiovascular system. It was reported that strong stress decreased blood fluidity.In this experiment, we investigated the relation between blood fluidity and water supply in rats loaded with forced exercise in high temperature environment.[Methods] SPF male Wistar rats weighing 250g were used. All animals were put in high temperature environment (Wet Bulb Globe Temperature; WBGT: 28°C) through whole experimental period. The rats were divided into four groups randomly; Suitable temperature environment-Exercise-Non water intake (SEN), High temperature environment-Exercise-Non water intake (HEN), High temperature environment-Exercise-Water intake (HEW) and Baseline (BL). In a group of water supply, distilled water was served before and later exercise by sonde forcibly. The blood was collected before or later of exercise and blood and erythrocyte suspension fluidity were measured.[Results] In the HEN, hydroperoxides, blood sodium, lactic acid and adrenaline increased while blood and erythrocyte suspension fluidity were decreased significantly compared with the BL. In addition, the hematocrit did not increase even if water equivalent to 4% of body weight lost it.[Conclusion] We speculate that exercise in high temperature environment decreases blood fluidity. However, the water supply in exercise that might not be sufficiently improve blood fluidity.

INFLUENCE TO BLOOD FLUIDITY BY EXERCISE IN RAT: INFLUENCE OF TRAINING IN HIGH TEMPERATURE ENVIRONMENTS / 体力科学

[Objective] Physical exercises raise more or less body temperature. A body temperature is regulated constantly generally by homeostasis mechanism. Perspiration is only heat radiation mechanism under high temperature environments. And sudoriferous water is supplied from blood. Blood flow is determined by blood fluidity, blood volume and the cardiovascular system. It was reported that strong stress decreased blood fluidity.In this experiment, we investigated the relation between blood fluidity and water supply in rats loaded with forced exercise in high temperature environment.[Methods] SPF male Wistar rats weighing 150 g were used. All animals were put in high temperature environment (Wet Bulb Globe Temperature; WBGT: 28°C) through whole experimental period. In a group of water supply, distilled water was served before and later exercise by sonde forcibly. The rats were divided into five groups randomly; Rest-Non water intake (RN), Rest-Water intake (RW), Exercise-Non water intake (EN), Exercise-Water intake (EW) and Baseline (B). The blood was collected before or later of exercise and blood fluidity or platelet aggregation was measured.[Results] In the EN, platelet aggregation, lactic acid and corticosterone increased while blood fluidity were decreased significantly compared with the RN, RW and EW. In addition, the hematocrit did not increase even if water equivalent to 8 % of body weight lost it.[Conclusion] We speculate that exercise in high temperature environment decreases blood fluidity. However, the water supply that does not completely make up for quantity of depletion in exercise may improve blood fluidity.

Evaluation on the combined effect of Sesamin and Schisandra extract on blood fluidity.

Several studies have demonstrated a link between blood viscosity and various forms of liver dysfunction. Therefore, we investigated the effect of liver protective herbal materials, Sesamin combined with extract of Schisandra chinensis berry (Schisandra) for its potential to improve blood fluidity in humans. Ten human subjects were recruited to study the effect of sesamin combined with schisandra extract (SCH) for two weeks on blood viscosity. Blood fluidity was measured as the transit time for 100mul of heparinized whole blood to pass through a micro-channel array setup at baseline, 1 week and 2 weeks. For safety assessment, blood biochemistry, hematology and urine analysis were taken at baseline, 1 week and 2 weeks after SCH administration. No safety concern and adverse effects were observed during the 2-week continuous intake period. Intake of SCH reduced blood passage time by 9.0% and 9.7% at 1 and 2 weeks, respectively. In conclusion, this pilot clinical study indicates that the combined administration of sesamin with schisandra extract could improve blood fluidity after 1 week of oral intake and this effect was sustained up to 2 weeks.

Relationship Between Diabetic Foot (DF) and the Change of Blood Fluidity / 医学研究杂志

Objective To study the relationship between diabetic foot(DF)and the change of blood fluidity.Methods The blood viscosity、plasma viscosity、hematocrit、erythrocyte sedimentation rate、fibrinogen were determined in 126 type 2 diabetes cases.They were divided into DF group and non-diabetic foot(NDF)group.Results ①The incidence of DF is higher in older and longer course of diabetes cases with renalpathy、neuropathy、peripheral artery disease and retinopathy.② The blood viscosity、plasma viscosity、hematocrit、erythrocyte sedimentation rate and fibrinogen are significantly higher in DF group.③ The indexes of blood fluidity are significantly higher in Ankle Brachial Index(ABI)abnormal group than normal group.Conclusions To have the blood fluidity under control effectively is very important for prevention and treatment of DF.

"Oketsu" and Hemorheological Changes-Examination by Micro Channel Array Flow Analyzer-(the first report) / 日本東洋医学雑誌

Scientific elucidation of “oketsu (blood stasis)” states is very important to understanding the diagnostic methods of oriental medicine. We investigated the correlation of blood fluidity to oketsu states, by micro channel array flow analyzer (MC-FAN). Twenty-seven female patients were divided into three groups: a non-oketsu group, a mildly affected group, and a severely affected group according to the diagnostic criteria of their oketsu syndrome. Immediately after collecting their venous blood, whole blood passage time was measured by MC-FAN. And we compared and investigated the correlation with degree of oketsu state, diagnostic criteria and changes of whole blood passage time after the administration of ku-oketsu drugs. As a result, whole-blood passage time of the mildly affected group and the severely affected group were significantly longer than that of the non-oketsu group, while the [an] improvement of blood fluidity was observed after medication. This study confirms that reduced blood fluidity is seen using MC-FAN in oketsu states, and that ku-oketsu drugs are able to improve these states.

The infiuence of physical exercise upon blood filtration time / 体力科学

We studied the effects of exercise on the blood fluidity. The subjects were 18 healthy males (21.6±0.8 yr, control : 5, soccer : 9, gymnastics : 4) . We measured the filtration time of whole blood by the Nuclepore filtration method as an index of blood fluidity. The filtration time at rest in the control group, soccer group, and gymnastics group was 59.8±11.9s, 42.5±15.1 s, 28.6±6.7s, respec tively. The filtration time at rest in the soccer group was significantly shorter than that in the control group (p<0.001) . There were no significant differences in filtration time at rest between the control and gymnastics groups, and between the soccer and gymnastics groups. The filtration time after single aerobic exercise was significantly prolonged compared with that before (p<0.001) . The filtration time before and after anaerobic exercise and muscular exercise was not significantly changed. The degree of filtration time prolongation was significantly lower in groups who drank water compared to groups who did not (p<0.001) . The effect of taking a sauna on filtration time was not significant. These results indicates the effect of aerobic exercise on blood fluidity, and the importance of water intake during exercise.