Plasma viscosity and cerebral blood flow

We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml. 100 g(-1). min(-1), respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98 to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1). min(-1) and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.     

血栓通注射液联合阿托伐他汀对急性脑梗死患者血脂和血液流变学的影响

目的:研究阿托伐他汀片与血栓通注射液联合治疗对脑梗死患者血脂及血液流变学的影响。方法:选取我院从2012年2月到2014年2月收治的急性脑梗死患者100例,分成两组,每组各50例。对照组静脉滴注血栓通注射液,试验组静脉滴注血栓通注射液加口服阿托伐他汀片治疗。14天后观察两个组的治疗效果,并且进行血脂(TC、TG、LDL-C、HDL-C)、血液流变学(血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数)等指标的检测,以及疗效及不良反应情况。结果:治疗后试验组TC、TG、LDL-C低于对照组,HDL-C高于对照组,且具有统计学意义(P0.05)。治疗后,试验组血浆粘度、全血高切粘度、全血低切粘度、全血还原黏度、纤维蛋白原、细胞刚性指数均低于对照组,且具有统计学意义(P0.05)。试验组总有效率为88.0%(44/50),高于对照组的66.0%(33/50)(P0.05)。试验组发生不良反应发生率与对照组比较无统计学意义(P0.05)。结论:阿托伐他汀片联合血栓通注射液对于脑梗死患者的血脂和血液流变学的影响疗效显著,且具有明显的降脂效果。     

In silico biophysics and hemorheology of blood hyperviscosity syndrome

Hyperviscosity syndrome (HVS) is characterized by an increase of the blood viscosity by up to seven times the normal blood viscosity, resulting in disturbances to the circulation in the vasculature system. HVS is commonly associated with an increase of large plasma proteins and abnormalities in the properties of red blood cells, such as cell interactions, cell stiffness, and increased hematocrit. Here, we perform a systematic study of the effect of each biophysical factor on the viscosity of blood by employing the dissipative particle dynamic method. Our in silico platform enables manipulation of each parameter in isolation, providing a unique scheme to quantify and accurately investigate the role of each factor in increasing the blood viscosity. To study the effect of these four factors independently, each factor was elevated more than its values for a healthy blood while the other factors remained constant, and viscosity measurement was performed for different hematocrits and flow rates. Although all four factors were found to increase the overall blood viscosity, these increases were highly dependent on the hematocrit and the flow rates imposed. The effect of cell aggregation and cell concentration on blood viscosity were predominantly observed at low shear rates, in contrast to the more magnified role of cell rigidity and plasma viscosity at high shear rates. Additionally, cell-related factors increase the whole blood viscosity at high hematocrits compared with the relative role of plasma-related factors at lower hematocrits. Our results, mapped onto the flow rates and hematocrits along the circulatory system, provide a correlation to underpinning mechanisms for HVS findings in different blood vessels.     

Effects of blood viscosity on renin secretion.

The effects of alterations in blood and plasma viscosities on plasma renin activity (PRA) were studied in dogs anesthetized with pentobarbital. Blood viscosity was altered by changing the hematocrit (Hct) level by isovolemic exchange using packed red blood cells or plasma. Plasma viscosity was elevated by isovolemic exchange using Hct-matched blood with high molecular weight dextran (Dx, mean m.w. approximately 450,000) dissolved in plasma. Following control measurements of plasma and blood viscosities, plasma [Dx], PRA, Hct and hemodynamic functions, the dog was subjected to isovolemic exchange transfusions to either alter the Hct or administer the Dx. Various measurements were repeated 40-60 min after each exchange. Arterial pressure and renal blood flow remained relatively constant after exchanges; increases in plasma and blood viscosities were accompanied by a decrease in renal vascular hindrance (vasodilation) to keep the renal flow resistance at control level. PRA rose with increases in plasma [Dx] and viscosity, and the rise in PRA was best correlated with the decrease in renal hindrance. The changes in PRA and renal hindrance have the same regression line whether blood viscosity was altered by Hct variation or Dx administration. The results indicate that increases in viscosity cause a compensatory vasodilation of renal vessels to cause renin secretion.     

Cerebral blood flow and blood viscosity in patients with polycythaemia secondary to hypoxic lung disease.

Blood viscosity, cerebral blood flow (CBF) and cerebral oxygen carriage (CBF X arterial oxygen content) were measured in 12 patients with polycythaemia secondary to hypoxic lung disease. CBF and cerebral oxygen carriage were both significantly higher than in a comparative group of 20 patients with raised packed cell volumes and normal lung function. The patients with secondary polycythaemia then underwent venesection and their mean packed cell volume fell from 0.613 to 0.495. This led to a consistent reduction in blood viscosity, which fell by 44% at a low shear rate (0.67/s) and 33% at a high shear rate (0.91/s). CBF rose by 21% (p less than 0.01), but cerebral oxygen carriage did not significantly increase in the group as a whole. Four of the patients with secondary polycythaemia had complained of episodes of confusion before venesection, which improved considerably once the packed cell volume had been lowered. Headache was relieved in a further two patients and none of the subjects was adversely affected by venesection. It was not possible, however, to show a correlation between symptomatic improvement and an increase in cerebral oxygen carriage.     

Alteration of blood hemorheologic properties during cerebral ischemia and reperfusion in rats

The cerebral ischemia and reperfusion rat model was employed in this experiment to study the rheological properties (i.e. viscosity, hematocrit, red blood cell deformability and thixotropic properties) of whole blood. The results of this study show that a significant relation exists between the duration of cerebral ischemia and reperfusion and the viscosity, hematocrit and thixotropic parameters of whole blood, but there is no significant influence on the deformability of RBC. Blood viscosity values declined gradually throughout the ischemia period, e.g., after 1h of ischemia, the values of whole blood viscosity under high, middle and low shear rates were 44, 28 and 23% lower than normal, respectively. Whereas after 1h of reperfusion, the values of viscosity increased rapidly to values 160, 57 and 41% higher than normal under the high, middle and low levels of shear rate, while the viscosity values after 12h of reperfusion tended to return to normal values. The values of hematocrit H and thixotropic parameter tau(0) and mu also gradually declined with the increase in the duration of ischemia, but increased significantly after 1h of reperfusion. The values of H, tau(0) and mu after 1h of reperfusion are significantly greater than that in the period of cerebral ischemia, the value of H, tau(0) is also higher than normal. With the increase in reperfusion time, H, tau(0) gradually returned to normal level, at the same time, mu also decreased.     

Blood viscosity studies in native and reconstituted polycythemic blood

In twelve subjects with Polycythemia vera (P.V.) whole blood, plasma and relative viscosities and the main factors capable of influencing such parameters (Hct, RBCs, WBCs and platelet count, total proteins, gamma-globulins and fibrinogen) were investigated. Ten normal subjects of similar age and sex were studied as control. Whole blood viscosity was determined both in basal conditions and after reconstitution of Hct to normal values by adding some autologous plasma. After the reconstitution of Hct the subjects studied were divided into two groups on the basis of the correlation between Hct and whole blood viscosity. The first group (group A) had a good correlation between Hct and whole blood viscosity; on the other hand the second group (group B) did not show any significant correlation between these two parameters after reconstitution. In basal conditions none of the parameters capable of influencing whole blood viscosity or plasma viscosity permitted any discrimination between the two groups. The relative viscosity, which represents an indirect index of red blood cell deformability, appears to be more elevated in group B. Therefore, the different behaviour of polycythemic blood after reconstitution of Hct might be conceived to be due to a difference in red cell deformability.     

Risk factors evaluation in some cardiovascular diseases

Cardiovascular risk factors are associated with limitations of blood fluidity. Rheological behaviour of blood in transient flow may result from the internal organization, which in turn depends upon many parameters, which may be considered as possible elements of a profiling algorithm for diagnostic and prognostic values in various pathophysiological states. This study was designed to investigate haemorheological parameters in patients being treated for hypertension, coronary heart disease and myocardial infarct. On the basis of plasma viscosity, whole blood viscosity, haematocrit, red cell aggregation and red cell deformation, the risk was evaluated. In cases of hypertension there was a significant rise in plasma viscosity, whole blood viscosity, red cell aggregation and a fall in red cell deformability. In cases of coronary disease, plasma viscosity and red cell aggregation was increased, while in patients with myocardial infarcts, where the degree of severity is greater it was found that there was a significant rise in both plasma and whole blood viscosity. Haematocrit values were unaffected in all three groups.     

Beneficial effect of fish oil on blood viscosity in peripheral vascular disease.

Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.     

No change of whole blood of plasma viscosity in cardiac patients after subcutaneous calcium heparin.

Whole blood viscosity, plasma viscosity and haematocrit were studied in a group of cardiac patients before and during subcutaneous heparin treatment. No significant change was noted in any of the parameters investigated. Relative viscosity (whole blood viscosity/plasma viscosity ratio) was also unaffected. These data indicate that heparin has no effect on the rheology of blood in vitro.     

Insensitivity of cerebral oxygen transport to oxygen affinity of hemoglobin-based oxygen carriers

The cerebrovascular effects of exchange transfusion of various cell-free hemoglobins that possess different oxygen affinities are reviewed. Reducing hematocrit by transfusion of a non-oxygen-carrying solution dilates pial arterioles on the brain surface and increases cerebral blood flow to maintain a constant bulk oxygen transport to the brain. In contrast, transfusion of hemoglobins with P50 of 4-34 Torr causes constriction of pial arterioles that offsets the decrease in blood viscosity to maintain cerebral blood flow and oxygen transport. The autoregulatory constriction is dependent on synthesis of 20-HETE from arachidonic acid. This oxygen-dependent reaction is apparently enhanced by facilitated oxygen diffusion from the red cell to the endothelium arising from increased plasma oxygen solubility in the presence of low or high-affinity hemoglobin. Exchange transfusion of recombinant hemoglobin polymers with P50 of 3 and 18 Torr reduces infarct volume from experimental stroke. Cell-free hemoglobins do not require a P50 as high as red blood cell hemoglobin to facilitate oxygen delivery.     

Detection of red cell aggregation by low shear rate viscometry in whole blood with elevated plasma viscosity

The viscosity of whole blood measured at low shear rates is determined partly by shear resistance of the red cell aggregates present, stronger aggregation increasing the viscosity in the absence of other changes. Effects of cell deformability can confound interpretation and comparison in terms of aggregation, however, particularly when the plasma viscosity is high. We illustrate the problem with a comparison of hematocrit-adjusted blood from type 1 diabetes patients and controls in which it is found the apparent and relative viscosities at a true shear rate of 0.20 s-1 are lower in the patient samples than age matched controls, in spite of reports that aggregation is increased in such populations. Because the plasma viscosities of the patients were higher on average than controls, we performed a series of experiments to examine the effect of plasma protein concentration and viscosity on normal blood viscosity. Dilution or concentration by ultrafiltration of autologous plasma and viscosity measurements at low shear on constant hematocrit red cell suspensions showed (a) suspension viscosity at 0.25 and 3 s-1 increased monotonically with plasma protein concentration and viscosity but (b) the relative viscosity increased, in concert with the microscopic aggregation grade, up to a viscosity of approximately 1.25 mPa-s but above this the value the relative viscosity no longer increased as the degree of aggregation increased in concentrated plasmas. It is suggested that in order to reduce cell deformation effects in hyperviscous pathological plasmas, patient and control plasmas should be systematically diluted before hematocrit is adjusted and rheological measurements are made. True shear rates should be calculated. Comparison of relative viscosities at low true shear rates appears to allow the effects of red cell aggregation to be distinguished by variable shear rate viscometry in clinical blood samples.     

Differential effect of cold acclimation on blood composition in rats and hamsters

Male rats and hamsters were exposed to a progressively lower air temperature and shorter photoperiod to simulate the onset of winter. Normothermic hamsters had a higher haematological oxygen carrying capacity (OCC) and coagulability (shorter prothrombin time and activated partial thromboplastin time) than rats. Cold acclimation significantly increased the OCC of rats, which parallels an increased metabolic rate, while no differences were observed in hamsters. Red cell transit time through filters was faster in the acclimated rats but not in hamsters, reflecting the lower mean cell volume due to a decreased rate of clearance from the circulation. Platelet counts were significantly lower in both cold-acclimated rats and hamsters, and there was a significant leucopenia in rats, which would reduce the degree of microvascular blockade. Whole blood viscosity, plasma viscosity, and serum osmolarity showed little change in either species. However, whole blood viscosity was significantly lower in cold-acclimated hamsters than control hamsters at the lowest shear rate tested (0.95 s(-1)). Interestingly, plasma viscosity and serum osmolarity were significantly lower in hamsters exposed to low temperatures for a shorter period (4 weeks), and may reflect the development of a reduced coagulability. These data suggest that blood composition in hamsters contributes to an innate tolerance of low temperatures, maintaining tissue perfusion under hypothermic conditions and aiding arousal from hibernation.     

补阳还五汤治疗高血压合并脑梗死的疗效及对血清PI3K/AKT信号通路的影响

摘要 目的：探讨补阳还五汤治疗高血压合并脑梗死的疗效及对血清磷脂酰肌醇-3激酶（PI3K）/丝氨酸-苏氨酸蛋白激酶（AKT）信号通路的影响。方法：选取2018年2月~2021年2月期间我院收治的高血压合并脑梗死患者100例,经随机数字表法分为观察组（补阳还五汤联合常规西医治疗,50例）和对照组（常规西医治疗,50例）,均治疗3周。对比两组治疗3周后的临床总有效率;对比两组治疗前、治疗3周后的血压[收缩压( SBP)、舒张压（DBP）]、神经功能及日常生活活动能力[美国国立卫生院神经功能缺损量表（NIHSS）评分、Barthel指数]、血液流变学指标（血浆黏度、全血低切黏度、全血高切黏度、纤维蛋白）及PI3K/AKT信号通路相关蛋白表达水平。结果：对照组的总有效率为74.00%,低于观察组的92.00%,两组对比有明显差异（P<0.05）。与对照组相比,观察组治疗3周后Barthel指数更高,NIHSS评分、DBP、SBP更低（P<0.05）。与对照组相比,观察组治疗3周后血浆黏度、全血低切黏度、全血高切黏度、纤维蛋白水平更低（P<0.05）。与对照组相比,观察组治疗3周后PI3K、AKT蛋白表达水平更低（P<0.05）。结论：补阳还五汤可有效改善高血压合并脑梗死患者的血液流变学、血压,提高日常生活活动能力,减轻神经功能损伤,同时还能下调 PI3K/AKT 信号通路相关蛋白表达水平。     

The effects of chronic long-term intermittent hypobaric hypoxia on blood rheology parameters

The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on blood rheology is not completely investigated. We designed this study to determine the effect of CLTIHH on blood rheology parameters. Present study was performed in 16 male Spraque-Dawley rats that divided into CLTIHH and Control groups. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mmHg; 5 hours/day, 5 days/week, 5 weeks). The control rats stayed in the same environment as the CLTIHH rats but they breathed room air. In the blood samples aspirated from the heart, hematocrit, whole blood viscosity, plasma viscosity, plasma fibrinogen concentration, erythrocyte rigidity index and oxygen delivery index were determined. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen concentration values in the CLTIHH group were found to be higher than those of the control group. However, no significant difference was found in erythrocyte rigidity index and oxygen delivery index between the groups. Our results suggested that CLTIHH elevated whole blood viscosity by increasing plasma viscosity, fibrinogen concentration and hematocrit value without effecting the erythrocyte deformability. Hence, CLTIHH that may occur in intermittent high altitude exposure and some severe obstructive sleep apnea (OSA) patients may be responsible for hemorheologic changes in those subjects.     

Non-Newtonian rheology of leukemic blood and plasma: are n and k parameters of power law model diagnostic?

When discussing the rheological properties of normal and leukemic blood it must be considered that blood is a suspension of cells in aqueous solution which is also known as plasma. Whole blood viscosity and plasma viscosity were determined by Rheometer LS30 which allows measuring whole blood and plasma viscosity in the middle and low shear rate ranges. The measurements of the viscosity showed that whole blood and plasma behave as non-Newtonian power law fluid. The values of n (non-Newtonian index) and k (consistency index) of power law fluid were calculated for both leukemic blood and plasma samples. The importance of this phenomenon for the micro-circulation is discussed.     

急性心肌缺血时低切变率下全血粘度变化机理研究

本实验旨在分析狗急性心肌缺血时低切变率下全血粘度异常升高与红细胞电泳率(EM)和血浆纤维蛋白原浓度变化间的关系。实验结果表明,阻断冠脉血流40min时,低切变率下全血粘度已显著升高,EM明显降低,二者呈高度负相关,此时血浆纤维蛋白原浓度仅轻度增加。缺血时间进一步延长时,EM逐渐恢复,而血浆纤维蛋白原浓度显著升高,此时低切变率下全血粘度升高主要与血浆纤维蛋白原变化有关。     

Transport of amino acids in the splanchnic bed by blood plasma and blood in the preruminant calf]

Three preruminant calves were fitted with catheters in portal and hepatic veins and in a mesenteric artery. Two electromagnetic flowmeter probes were clipped around the portal vein and the hepatic artery. The calves were fed either a diet with a low (L) or a high (R) abomasal emptying rate for dietary proteins. Blood flow and free amino acid levels in plasma (P) and blood (S) were determined before the morning meal and during the following 7 h. In the portal vein, for most amino acids P/S ratios were correlated to the net amino acid balance of the digestive tract measured in plasma. By contrast in the hepatic vein, these ratios were mainly correlated to hepatic balance measured in whole blood. Correlations between digestive tract and hepatic balance calculated using either plasma or whole blood pool were different for some amino acids. This suggests that amino acid exchange between plasma and blood cells is low and absorbed amino acids are mainly transported to the liver by plasma, whereas whole blood rather than plasma is concerned in amino acid exchanges in the liver.     

Effect of nonaxisymmetric hematocrit distribution on non-Newtonian blood flow in small tubes

Hematocrit distribution and red blood cell aggregation are the major determinants of blood flow in narrow tubes at low flow rates. It has been observed experimentally that in microcirculation the hematocrit distribution is not uniform. This nonuniformity may result from plasma skimming and cell screening effects and also from red cell sedimentation. The goal of the present study is to understand the effect of nonaxisymmetric hematocrit distribution on the flow of human and cat blood in small blood vessels of the microcirculation. Blood vessels are modeled as circular cylindrical tubes. Human blood is described by Quemada's rheological model, in which local viscosity is a function of both the local hematocrit and a structural parameter that is related to the size of red blood cell aggregates. Cat blood is described by Casson's model. Eccentric hematocrit distribution is considered such that the axis of the cylindrical core region of red cell suspension is parallel to the axis of the blood vessel but not coincident. The problem is solved numerically by using finite element method. The calculations predict nonaxisymmetric distribution of velocity and shear stress in the blood vessel and the increase of apparent viscosity with increasing eccentricity of the core.     

Blood viscosity parameter correlation with types of leukemia.

We investigated the hemorheological, hematological and biochemical parameters in 30 cases of acute lymphocytic leukemia (ALL), 21 cases of acute myelogenous leukemia (AML) and 30 cases of chronic myelogenous leukemia (CML). The parameters studied include whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), red cell filterability, hematocrit, platelet count and aggregation, fibrinogen, hemoglobin, leucocyte count, bleeding time and lactate dehydrogenase activity (LDH). In the cases of ALL we observed significant decrease in whole blood viscosity, hemoglobin, hematocrit and platelet count but an increase in plasma viscosity, fibrinogen, bleeding time and LDH activity. In the cases of AML, we observed increase in whole blood viscosity, plasma viscosity, ESR, fibrinogen, leucocyte count, bleeding time and LDH activity but decrease in the hemoglobin, hematocrit and platelet count. In the cases of CML, we observed an increase of whole blood viscosity, plasma viscosity, ESR, fibrinogen elevation but decreases in bleeding time. In all cases, red cell filterability was unaffected.