Regional and systemic hemorheological disorders during feet diabetic gangrene

We investigated the RBC aggregability in the patients with the foot diabetic gangrenes: in the venous blood samples taken from the damaged foot before its amputation, as well as from the cubital vein (the systemic circulation). The RBC aggregability was investigated with the "Georgian technique" that is sensitive and provided us with direct and quantitative data. We found that the RBC aggregability was higher by about 20%, in the blood flowing from the gangrenous tissue than in the systemic circulation. Therefore, the sources of the systemic hemorheological disorders were the primarily damaged tissues. Taking into account that the blood is uninterruptedly flowing and mixing together in the whole circulatory bed we conclude that in the systemic circulation a certain compensatory mechanism provide for a partial normalization of the blood rheological properties, since the RBC aggregability never reaches the level in the blood of the healthy people.     

Microcirculatory Stasis Induced by Hemorheological Disorders: Further Evidence

Objective : Reinvestigate the microcirculatory alterations immediately responsible for blood rheological disorders and blood stases, which are related to red blood cell (RBC) aggregation in capillaries. Methods : Blood rheological disorders were produced by significantly intensified intravascular red blood cell aggregation in the intestinal mesentery of Wistar rats and in the cerebral cortex of Chinchilla rabbits, either systemically (by intravascular administration of high molecular-weight dextran) or locally (by increase of high-molecular compounds in blood plasma inside individual or groups of capillaries). Results : Under conditions where the microvascular lumina were not decreased and the arteriolovenular pressure gradients got even higher, the significantly enhanced intravascular RBC aggregation resulted in the slowing down of blood flow in the microvessels to a full stop. Conclusion : A significant increase in microvascular RBC aggregation results in local hemorheological disorders, which is, in all probability, related to derangement of the blood-flow structuring in microvessels.     

Hemorheological disorders during ischemic brain infarcts in patients with and without diabetes mellitus

The aim of the present study was the comparative analysis of the role of specific hemorheological derangements in the pathogenesis of ischemic brain infarcts with and without diabetes mellitus. Blood plasma viscosity, as well as red blood cells (RBC) aggregability were quantitatively investigated in all patients during the study. Both of the above mentioned indices of hemorheological disorders were significantly higher in the patients with brain infarcts and diabetes mellitus as compared to the control and the group of ischemic brain infarcts without diabetes. During the ischemic stroke, blood plasma viscosity was increased by a mean of 9.2 per cent in the first and by a mean of 17.6 per cent in the second group of patients. As to the erythrocyte aggregability index, it was changed considerably more - by a mean of 113.8 per cent during stroke without diabetes, while in the diabetic patients the RBC aggregability index was found to be increased by a mean of 147.3 per cent. Ischemic brain infarcts in patients with diabetes mellitus were associated with a significant increase of the patients' blood rheological disorders in all the investigated cases.     

Comparison of blood rheological changes in the microcirculation during experimental hemorrhagic and traumatic shock

OBJECTIVE: The aim of the present study was the analysis of the specific hemorheological disorders during the middle stages of experimental traumatic and hemorrhagic shock. METHODS: The following hemorheological properties were investigated: Red Blood Cell (RBC) aggregability, their deformability, and systemic hematocrit. The RBC aggregability was assessed by using the "Georgian technique". The RBC deformability was determined with the nuclepore membrane filter method of Reid. The hematocrit was measured by blood centrifugation. The results obtained were treated statistically by using the "Two sample T-test". RESULTS: We found that in the animals with traumatic shock the erythrocyte aggregability index increased by mean 181%, while in the hemorrhagic group this index on contrary decreased by mean 68% as compared to control group; The RBC deformability underwent a significant decrease during both traumatic and hemorrhagic shock: by a mean of 52% during the first and 62% during the second one. The systemic hematocrit decreased by a mean of 45% during the traumatic shock and by a mean of 50% during the hemorrhagic shock. CONCLUSION: The data obtained provide evidence that the hemorheological disorders are among the most significant microcirculatory disturbances in the pathogenesis of both the traumatic and the hemorrhagic shock.     

Blood rheological properties and lipid peroxidation in cerebral and systemic circulation of neurocritical patients

The present study was aimed at investigating the red blood cell (RBC) aggregation and the parameters of lipid peroxidation - malondialdehyde (MDA) and MDA + 4-hydroxyalkenals (HAE) - in the blood of critically deteriorated stroke patients (brain infarcts, parenchymatous and subarachnoid hemorrhages) and in the control group. Measurements were made in blood samples from the common carotid artery, the both internal jugular and cubital veins. The RBC aggregation index was found to increase by about 80 per cent in both the cerebral and systemic circulation as compared to the control blood samples. MDA content appeared also significantly higher in the blood flowing out of the damaged hemisphere of the neurocritical patients as compared to the control group. In the blood flowing out of the damaged hemisphere of the neurocritical patients MDA as well as MDA + HAE content significantly exceeded the values found in blood samples of the jugular vein of the contralateral hemisphere, carotid artery and the cubital vein. The results of this study suggest a certain interdependence between the blood plasma lipid peroxidation and the RBC aggregation in the brain vessels following its damage.     

Blood rheology as a marker of venous hypertension in patients with venous disease

During chronic venous insufficiency (CVI), several microvascular functional abnormalities, due to venous hypertension, develop. To look for blood rheological consequences of venous hypertension "VH", whole blood viscosity and its main determinants were measured in 11 normal controls and 36 patients with CVI exposed to a short-term experimental VH. Patients were subdivided into 2 groups according to the severity of their disease. Blood was taken from a foot vein before and after VH, which was induced by appling a pneumatic tourniquet to 100 mmHg for 15 minutes. Whole blood viscosity at low and high shear rates, red blood cell (RBC) aggregation, RBC rigidity, plasma viscosity and proteins as well as red and white blood cell (WBC) counts were recorded. Patients at baseline, i.e., before application of the tourniquet, showed several hemorheological abnormalities such as an increased RBC aggregation, increased low shear rate viscosity, and a significant elevation in plasma fibrinogen level. Patients with more severe CVI had more marked hemorheological changes. The short term VH in patients led to further aggravation of these changes. There were also at baseline lower values, however not significantly, of hematocrit and RBC count, suggesting that hemoconcentration is not a feature of CVI. These same parameters were slightly, however not significantly, increased after VH, indicating a fluid escape into the extravascular space. A significant fall in WBC count was also observed after VH, in keeping with the white cell trapping hypothesis. In conclusion, even a short-term VH is able to induce several hemorheological impairments, which are probably involved in the failure of the microcirculation and hence the initiation of tissue damage in patients with CVI.     

Comparison of erythrocyte aggregability changes during ischemic and hemorrhagic stroke

The aim of this work was to perform a comparative investigation of erythrocyte aggregability changes in the peripheral and cerebral circulation during ischemic and hemorrhagic stroke. Subjects of the present study were patients with ischemic brain infarcts (14 patients) and with hemorrhagic stroke (21 patients) from the Intensive Care Unit of the Institute of Neurology and Neurosurgery. The blood samples were obtained from the following blood vessels: the common carotid artery carrying blood to the primarily damaged brain hemisphere, both jugular veins carrying blood from the primarily damaged and the contralateral hemispheres, as well as from the cubital vein to obtain specimens of the systemically circulating blood. Erythrocyte aggregation was evaluated by using the "Georgian technique". We found that the RBC aggregation indices increased in both the regional as well as the systemic circulation of the hemorrhagic stroke patients as compared to ischemic stroke patients. The results of the present study demonstrate different changes of erythrocyte aggregation in ischemic and hemorrhagic stroke patients. Therefore, the role of blood rheological properties in their pathogenesis seems also to be different.     

Microcirculation and blood rheology in patients with cerebrovascular disorders

We estimated hemorheological parameters of vein blood samples and cutaneous microvascular blood flow in patients with acute ischemic stroke and in controls. The worsened blood rheological properties were registered in patients with stroke: the enhanced whole blood viscosity was due to the substantial increase of plasma viscosity and the impairment of microrheological blood properties: elevated erythrocyte aggregability and decreased deformability compared to the healthy group. The decrease of oxygen consumption fixed by rheological methods and by laser Doppler flowmetry led us to conclude that the tissue hypoxia took place in patients with stroke. The regulatory mechanisms aimed to maintain blood supply to tissue were activated under cerebral infarction and the impact of unfavorably changed rheological blood properties was markedly enhanced. Revealed close interrelations between rheological and microcirculation parameters testified the important role of hemorheological factors in maintenance of microvascular blood flow and oxygen delivery to tissue.     

Evaluation of the hemorheological and neurosonographic relationship in patients with cerebrovascular diseases

During the last fifteen years some of our priority scientific topics of research were hemorheological and neurosonographic investigations in 229 patients with different forms of cerebrovascular diseases (CVD): 75 patients with asymptomatic CVD (ACVD), 65 patients with transient ischemic attacks (TIAs) and 89 patients with chronic unilateral cerebral infarctions (UCI). The findings were compared with 70 healthy persons. The main estimated hemorheological parameters were hematocrit (Hct), apparent whole blood viscosity (WBV), plasma viscosity (PV) and fibrinogen (Fib). They were correlated with the following sonographic parameters, obtained by extracranial and transcranial Doppler sonography: blood flow velocities (BFV) and peripheral resistance index of Pourcelot (RP) of the major arteries of the head and the basal cerebral arteries and vasomotor reactivity indices (VMRI) of the middle cerebral arteries (MCA). Among the hemorheological variables the correlations of Hct with the velocity sonographic parameters predominated in all groups. Significant positive correlations between Hct, WBV and the RP of the internal carotid artery and MCA were found in patients with CVD. In UCI the increase in Hct and Fib was associated with a decrease in BFV of the collateral circulation where aging and high mean blood pressure were additional risk factors for impairment of the cerebral hemodynamics. Plasma viscosity was found to correlate with cerebral VMRI of MCA in patients with UCI. The clinical impact of these findings and their relation to the therapeutic strategy in CVD are discussed.     

Blood rheology and aging

The flow properties of blood play significant roles in tissue perfusion by contributing to hydrodynamic resistance in blood vessels. These properties are influenced by pathophysiological processes, thereby increasing the clinical relevance of blood rheology information. There is well-established clinical evidence for impaired blood fluidity in humans of advanced age, including enhanced plasma and whole blood viscosity, impaired red blood cell (RBC) deformability and enhanced RBC aggregation. Increased plasma fibrinogen concentration is a common finding in many studies owing to the pro-inflammatory condition of aged individuals; this finding of increased fibrinogen concen-tration explains the higher plasma viscosity and RBC aggregation in elderly subjects. Enhanced oxidant stress in advanced age is also known to contribute to altered blood fluidity, with RBC deformability being an important determinant of blood viscosity. Several studies have shown that physical activity may improve the hemorheological picture in elderly subjects, yet well-designed observational and mechanistic studies are required to determine the specific effects of regular exercise on hemorheological parameters in healthy and older individuals.     

Arteriolar resistance and hemorheological disorders related to Raynaud's phenomenon

The functional condition of resistance arteries in human hands was monitored with a noninvasive test. Blood flow velocity changes (Doppler flow meter) were monitored in the radial artery before and after a 1-min stop flow in the hand under conditions of stable systemic arterial pressure. In addition, the most significant parameter of hemorheological disorders in microcirculation, RBC aggregability, was investigated in the same patients' blood samples. The muscular tone of the resistance arteries was found to be a mean of 35% higher during Raynaud's phenomenon than in the healthy controls tested. The raised vascular tone was not related to the patients' age and had a pronounced tendency to rise with disease duration. RBC aggregability was a mean of 4% higher in the patients than in the healthy controls, and the difference was not reliable. We concluded that, among principal pathogenic factors which might cause deficiency of the blood supply to fingers, it is the enhanced tone of resistance arteries that is primarily responsible for the development of Raynaud's phenomenon, while hemorheological disorders are not, or are considerably less, involved in the development of the principal symptom of the disease, deficient blood supply to the fingers.     

The effect of simvastatin therapy on hemorheological profile in coronary heart desease (CHD) patients

This study was designed to examine changes of hemorheological parameters in patients with CHD and hypercholesterolaemia (wide range of plasma total cholesterol level from 5.6 to 9.8 mmol.l-1) subjected to lipid lowering therapy with statins (simvastatin, 10.0-20.0 mg/day, dosage was dependent on an initial level of total cholesterol). Twenty female subjects were enrolled in this research program. Both prior to and following drug treatment for eight weeks, hemorheological measurements included plasma viscosity, high and low shear whole blood viscosity, hematocrit, RBC aggregation and rigidity. Treatment with simvastatin significantly (p<0.05) reduced total cholesterol, total triglycerides and low-density lipoprotein cholesterol (LDL-C). However, the hemorheological effects of lipid lowering therapy differed markedly between macro- and microrheological groups of parameters: plasma and whole blood viscosity were not significantly changed whereas RBC aggregation and its rigidity were decreased significantly after statin treatment. These results thus suggest that the rheologic effect of lipid lowering therapy concerned mainly the microrheological parameters: red cell aggregation and deformability.     

Comparative values of erythrocyte aggregability versus other indices of hemorheological disorders in patients with ischemic brain infarcts

The aim of the present study is comparison of changes of principal hemorheological factors responsible for blood flow disorders in the microcirculation in patients with ischemic brain infarcts. It was found that in venous blood samples the erythrocyte aggregability (examined with a direct, highly sensitive, quantitative technique) was considerably more increased (by mean of 120%) than the blood plasma fibrinogen contents, blood plasma viscosity, and hematocrit which increased only by 23.7%, 7.4% and 3.6%, respectively, as compared to the same hemorheological factors in the healthy controls. These results led us to the following conclusion: among the other tests the enhanced erythrocyte aggregability, when measured with an appropriate technique, is the best diagnostic indicator of hemorheological derangements during development of the ischemic brain infarct.     

Alterations in erythrocyte membrane. Effect of neutrophil activation

White blood cells, especially polymorphonuclear neutrophils (PMN), are known to alter some hemorheological parameters. Most of in vitro results have been obtained with passive PMN. Stimulated PMN also lead to other hemorheological changes. In our study, we have firstly activated PMN with opsonized zymosan and collected a PMN-free supernatant after 30 minutes activation. This supernatant was secondarily incubated with erythrocytes either in whole blood or in suspension. After 10 minutes incubation, hemorheological parameters were evaluated: 1) red blood deformability (RBC) (Ektacytometer* Technicon), 2) RBC filtration (Hemorheometer MK 1), 3) RBC aggregation (Erythroaggregometer* Sefam), 4) Plasmatic and whole blood viscosities (Low Shear 30* Contraves). Our results show that activated PMN-supernatant increases rigidity index (IR) of RBC in suspensions (IR of RBC control = 14.59 +/- 3.30 towards RI of incubated RBC = 22.91 +/- 7.06 p less than 0.001). Other rheological parameters remain unchanged. Activated PMN suspenatant influence on RBC is slight but could suggest of an alteration of RBC membrane. With an in vitro model of washed platelets aggregation, we have previously demonstrated that proaggregant activity of PMN supernatant was inhibited by specific Platelet-Activating Factor (PAF-acether) antagonists: BN 52021, BN 50723, Web 2086. We have so compared both effects of activated PMN-supernatant and synthetic PAF-acether on RBC membrane fluidity. Membrane fluidity was studied by fluorescence polarization of 4 probes embedded at different deep in the membrane of intact RBC. Similar modifications of RBC membrane fluidity are observed with either synthetic PAF-acether or PMN supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of antihypertensive therapy on hemorheological profiles in female hypertensive patients with initially low or high whole blood viscosity

This study was designed to examine changes of hemorheological parameters in essential arterial hypertension subjects following antihypertensive drug therapy. Eighty two female subjects were enrolled, and sub-divided into two groups based upon their high shear whole blood viscosity being lower (L) or higher (H) than normal controls. Equal numbers of L and H subjects were then treated for four weeks with one of four agents: angiotensin-converting enzyme inhibitor (ACE-inhibitor, Spirapril - 6 mg/day); calcium antagonist (Isradipin - 5 mg/day); beta-1-blocker (Talinolol - 100 mg/day); diuretic (Indapamide - 1.5 mg/day). Both prior to and following drug treatment for six weeks, hemorheological measurements included plasma viscosity; high and low shear whole blood viscosity, hematocrit, fibrinogen and RBC aggregation. Treatment with each of the four drugs significantly (p<0.05) reduced blood pressure in both the L and H groups. However, the hemorheological effects of antihypertensive drug therapy differed markedly between groups: plasma and whole blood viscosity were significantly elevated in the L groups whereas these parameters were significantly decreased in the H groups. Fibrinogen levels and RBC aggregation decreased in both groups, whereas hematocrit was unaffected. These results thus suggest that the rheologic effects of antihypertensive drug therapy depend strongly on the initial, pre-treatment status of the subject, and that for some subjects, such therapy can result in adverse hemorheological alterations.     

小动脉硬化性脑小血管病与睡眠障碍

研究显示,脑小血管病可通过脑组织损害影响神经回路、局部脑血流量改变及神经内分泌改变等机制造成睡眠障碍,且脑小血管病所致的卒中后抑郁和脑萎缩均可能与睡眠障碍有关.反过来,睡眠障碍可损害血脑屏障和脑血管自动调节功能,增高脑小血管病的发病风险.两者相互联系,互为因果,共同影响患者预后和生存质量.     

Plasma-erythrocyte viscosity and evaluation of several pro- and anti-aggregating factors in NIDDM patients in metabolic decompensation state]

In NIDDM diabetic subjects, the microcirculatory damage shows a double aspect: an alteration of the vascular wall, particularly of the arteriolar capillary, and a hemorheological alteration at the level of the capillary district. In the microcirculation, because of the low velocity of the flow and the inverse relationship between capillary size and RBC diameter, the viscosity has an important role with its components: RBC viscosity and deformability. Even the erythrocyte aggregation has a key role as resultant of the attracting and repulsing forces, among which the plasma-RBC viscosity and the deformability play opposite role. Our method allows to evaluate the erythrocyte, the whole blood, the plasma and the plasma-RBC viscosity, and the deformability. Studies from this laboratory in NIDDM subjects show an increase in the blood viscosity, a decrease in the erythrocyte deformability and plasma-RBC viscosity. It is suggested that in microcirculatory district the flow reductions are particularly of hemorheological type and that the sludged blood is an "optical" phenomenon with poor meaning. We consider some hematological parameters, namely the Hgb A1c %, Hgb concentration, RBC count, MCV, etcetera.     

Blood rheology and hemodynamics

Blood is a two-phase suspension of formed elements (i.e., red blood cells [RBCs], white blood cells [WBCs], platelets) suspended in an aqueous solution of organic molecules, proteins, and salts called plasma. The apparent viscosity of blood depends on the existing shear forces (i.e., blood behaves as a non-Newtonian fluid) and is determined by hematocrit, plasma viscosity, RBC aggregation, and the mechanical properties of RBCs. RBCs are highly deformable, and this physical property significantly contributes to aiding blood flow both under bulk flow conditions and in the microcirculation. The tendency of RBCs to undergo reversible aggregation is an important determinant of apparent viscosity because the size of RBC aggregates is inversely proportional to the magnitude of shear forces; the aggregates are dispersed with increasing shear forces, then reform under low-flow or static conditions. RBC aggregation also affects the in vivo fluidity of blood, especially in the low-shear regions of the circulatory system. Blood rheology has been reported to be altered in various physiopathological processes: (1) Alterations of hematocrit significantly contribute to hemorheological variations in diseases and in certain extreme physiological conditions; (2) RBC deformability is sensitive to local and general homeostasis, with RBC deformability affected by alterations of the properties and associations of membrane skeletal proteins, the ratio of RBC membrane surface area to cell volume, cell morphology, and cytoplasmic viscosity. Such alterations may result from genetic disorders or may be induced by such factors as abnormal local tissue metabolism, oxidant stress, and activated leukocytes; and (3) RBC aggregation is mainly determined by plasma protein composition and surface properties of RBCs, with increased plasma concentrations of acute phase reactants in inflammatory disorders a common cause of increased RBC aggregation. In addition, RBC aggregation tendency can be modified by alterations of RBC surface properties because of RBC in vivo aging, oxygen-free radicals, or proteolytic enzymes. Impairment of blood fluidity may significantly affect tissue perfusion and result in functional deteriorations, especially if disease processes also disturb vascular properties.     

A型行为与脑梗死及血液流变学的相关性研究

目的　研究A型行为 (TAB)与脑梗死及血液流变学的关系 ,为脑梗死的预防提供依据。方法　采用 1∶1配对病例对照设计 ,应用全国心身医学协作组编制的“A型行为类型问卷”对 2 45例脑梗死患者及 2 45名健康对照进行问卷调查 ;并随机筛选出A型行为脑梗死患者 (TAB组 )和与之相匹配的非A型行为脑梗死患者 (非TAB组 )各 5 0例 ,同时随机选取TAB和非TAB健康人员各 5 0名作为对照组 ,4组受试者均于晨 6时空腹抽静脉血进行血液流变学检测。结果　脑梗死组TAB者占 79.5 % ,对照组TAB者占 5 4.8% ,优势比值为 3.16 (95 %可信限为 2 .0 6～ 4.84,P <0 .0 0 5 )。TAB组患者全血低切粘度 (1s- 1 )、血浆粘度 (10 0s- 1 )、红细胞聚集指数及血浆纤维蛋白原显著高于非TAB组及对照组 (P <0 .0 5 )。结论　A型行为可能是导致脑梗死的危险因素之一 ;对A型行为给与适当的干预 ,应是脑梗死一级预防的内容之一。     

Hemorheological abnormalities in stable angina and acute coronary syndromes

The pathophysiological abnormalities of stable angina (SA) and acute coronary syndromes (ACS) may, in part, be promoted by fluid forces associated with local blood flow and hence by the rheological properties of blood. This study evaluated several hemorheological parameters in 16 healthy controls and in 16 SA, 18 unstable angina (UA) and 19 acute myocardial infarct (AMI) patients; all patients underwent diagnostic angiography following blood sampling. Rheological measurements included whole blood viscosity, plasma viscosity and RBC aggregation via erythrocyte sedimentation rate (ESR) and Myrenne aggregometer indices. Compared to controls, RBC aggregation was significantly elevated in all patient groups (p<0.001), with the rank being AMI>UA>SA. RBC aggregability as tested in 70 kDa dextran exceeded control in all patients. Blood viscosity values calculated at 40% Hct, plasma viscosity and yield shear stress values followed the same pattern (AMI>UA>SA>control); increases of inflammatory markers (i.e., WBC count, hs-CRP) were elevated in all patient groups in the order AMI>UA>SA. Our study thus indicates an association between hemorheological abnormalities and the severity of coronary artery disease, and suggests the merit of evaluating whether therapeutic interventions that normalize blood rheology may reduce the incidence and/or progression of coronary artery disease.