Activated leukocytes generate oxygen free radicals and cause injury in a variety of surrounding cells. Red blood cells (RBC) are among the most susceptible cells to this injury. Deformability, lipid peroxidation and membrane proteins were investigated in RBC after incubation with activated granulocytes (2 hours, at 37 QC), obtained from guinea pigs with experimental sepsis. A second group of experiments was conducted with non-activated granulocytes isolated from blood of healthy guinea pigs. RBC transit time through S 11m pores measured by a cell transit analyzer was 3.2S±0.12 msec and 2.86±0.02 msec in the suspensions containing activated and non-activated granulocytes, respectively (p<O.OS). Addition of superoxide dismutase (SOD) (20 Ilg/ml) and catalase (40 Ilg/rnl) inhibited the effect of activated granulocytes on RBC deformability. Lipid peroxidation was also increased under the influence of activated granulocytes (31.S0±3.36 nmol/grHb versus 20.02±2.97 nmol/grHb); SOD failed to prevent this increment, while catalase was found to be effective. A widening of Band 1 (spectrin) was observed in SDS-PAGE electrophoresis of membrane proteins of RBC incubated with activated granulocytes, indicating spectrin-hemoglobin crosslinking. This alteration was prevented by both SOD and catalase, as in the case of transit time. The superoxide radical seems to be responsible for the membrane protein and mechanical alterations, while lipid peroxidation was induced by a different oxidative mechanism.
The effects of albumin on orientation and deformation for RBCs in a shear now field of low viscosity have been studied with a new Ektacytometry proposed by ourselves. The results show that orientation index (DI)(or) for blood sample of albumin concentration <0.04g/L quickly increase with the albumin concentration and (DI)(or), for blood sample of albumin concentration of 0.04g/L reach maximum value while (DI)(or) for blood sample of albumin concentration >0.5g/L intend to a stable value. From rheological point of view, above-mentioned results were explained. Based on this, the optimum albumin concentration far studying microrheology of RBC was selected. The results also show that (DI)(or) just depends on the deformability and the morphology of RBC and it doesn't correlate with the lipid fluidity of RBC membrane, and that the new Ektacytometry is better than traditional Ektacytometry in studying microrheology of RBC membrane.
The sensitivity of the Cell Transit Analyzer (CTA) to the alterations of red blood cell (RBC) deformability and related factors was investigated. Using 5 mu m pore size filters the CTA was found to be more sensitive to slight glutaraldehyde-induced decreases of deformability for rat RBC in comparison with larger human RBC. However, using 3 mu m pore size filters decreased the sensitivity of measurements to mechanical changes of rat RBC, implying that a lower cell/pore size ratio might provide better sensitivity. Exclusion of a subpopulation of the most rigid cells, which are not able to pass through the pores might be involved. Measurements using RBC suspensions with various cell counts revealed that RBC concentration in the suspension being filtered was an important determinant of CTA sensitivity, especially for measurements on human RBC using 5 mu m pore size filters. The insensitivity of CTA to slight changes in deformability might, in part, be related to the higher probability of longer pulses being rejected as a result of coincidence. Either decreasing the cell/pore size ratio or limiting the cell count in the suspensions being filtered might optimize the sensitivity of the CTA to slight degrees of mechanical alterations in human RBC. Copyright (C) 1996 Elsevier Science Ltd.
The hemorheological properties and transcutaneous oxygen pressure ''TcPO2'' are studied in both 20 healthy subjects and 36 insulin-dependent diabetic ''IDD'' patients without micro and macroangiopathy Patients are classified on the basis of having HbA1C values either persistently below 7.5 % (D1 : 23 with good metabolic control) or persistently above 7.5 % (D2 : 13 with poor metabolic control). RBC aggregation is shown to be more important in patients while TcPO2 values are decreased. Impairements are more marked in diabetics of group D2 than either those of group D1 or the healthy subjects. These results suggest that a poor metabolic control is associated with abnormalities in both RBC aggregation and TcPO2.Furthermore, the effects of a 3-year intensive insulin therapy is studied. In this study, 34 IDD patients are selected on the basis of having a poor metabolic control. The therapy is found to improve the HbA1C level in 68 % of patients (D3 n=23) while 32 % (D4 n=11) remained with a persistent poor metabolic control. In group D3, RBC aggregation and TcPO2 are shown to be improved consistently with HbA1C decrease. In contrast, in group D4, both hemorheologic and microcirculatory disturbances persist despite of the intensive insulin therapy. These results confirm that disturbances in RBC aggregation and TcPO2 can be resulted from a poor and chronic metabolic control. Besides, they underline that beneficial effects on these parameters, can be obtained from an intensive insulin therapy. Copyright (C) 1996 Elsevier Science Ltd
We measured the platelet activation and the rate of erythrocyte aggregation simultaneously employing venous blood from 31 patients with cerebral infarction during the acute phase (less than 7 days after onset) and 73 patients with cerebral infarction during the chronic phase (more than 1 month after onset.). The degree of platelet activation was estimated from the levels of plasma beta-thromboglobulin (BTG), platelet factor 4 (PF4), and thrombospondin (TSP). The erythrocyte aggregation rate was examined using the whole-blood erythrocyte aggregometer developed by us (Am. J. Physiol. 251, H1205-H1210, 1986) with concomitant measurement of the fibrinogen concentration. The mean values of the erythrocyte aggregation rate, plasma BTG, PF4, TSP and fibrinogen concentration at the acute phase of cerebral infarction were statistically significantly (P<0.05) higher than those at the chronic phase of cerebral infarction or in the control group, Multiple regression analysis revealed that fibrinogen, BTG and TSP were main factors contributing to the enhanced erythrocyte aggregation rate at the acute phase of cerebral infarction, but fibrinogen was the sole contributing factor at the chronic phase of cerebral infarction. We conclude that the platelet activation, erythrocyte aggregation rate and fibrinogen concentration were closely correlated with each other in patients with cerebral infarction during the acute phase.
In this paper, an analytical comparison is made between the normal values of 1372 determinations of whole blood viscosity (230s(-1)) from healthy female and five geographical factors in China's 23 areas. It is found that altitude is the main factor affecting the normal values of whole blood viscosity (230s(-1)). As altitude increases, the normal value of women whole blood viscosity also increases gradually. Applying the method of mathematical regression analysis, five formulas of univariate regression equations and a formula of multivariate regression equation are given. If geographical index values of altitude (X(1)), latitude (X(2)), relative humidity (X(3)), annual average temperature (X(4)), annual precipitation (X(5)) in some place are known, the normal value of women whole blood viscosity (230s(-1)) in this area can be assessed according to the multivariate regression equation, Y = 8.49 + 0.000424X(1) - 0.0559X(2) - 0.00684X(3) + 0.0151X(4) -0.00116X(5) +/- 0.58.
Systemic hemorheologic abnormalities may play a role in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients versus age matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and theologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at the last follow-up visit 36 months post-treatment for the treated group compared with the control group. The retinal blood flow parameters were markedly improved soon after the institution of therapy and may have contributed to the improved visual prognosis in the treated patient group.
Patients suffering from acute ischemic stroke have impaired cerebral autoregulation. For this reason, the perfusion of the penumbra depends directly on BP and CO. The CO can be increased by hypervolemic hemodilution and administration of positive inotropic drugs. In the present study, we examined the effect of different therapy protocols on hemodynamics in three patient groups. In patients with no manifest cardiac insufficiency, suffering from nonacute cerebrovascular diseases (group 1, n=6) we carried out a hypervolemic hemodilution with an initial loading dose. In a second group of patients (group 2, n=6), suffering from an acute stroke and limited cardiac capacity, we combined hypervolemic hemodilution with administration of digitalis. In a third group of patients, suffering from an acute stroke, without manifest cardiac insufficiency, we combined hypervolemic hemodilution with the administration of sympathomimetics (group 3, n=6). Group 1 showed a rapid, 15% increase in CO that lasted approximately 3 hours. Group 2 showed a slow improvement in CO, which became apparent during the course of the therapy. Group 3 showed a rapid and lasting increase in CO of more than 30% which correlated closely with the administered dopamine/dobutamine dose. Hypervolemic hemodilution alone does not result in a rapid and longlasting increase of CO, particularly not in patients with myocardial insufficiency. To improve the hemodynamic status of acute stroke patients, the administration of positive inotropic substances is a viable alternative.
Normal Hemorheology: Plasma proteins, plasma viscosity, and red blood cell (RBC) aggregation are very low in the fetus and the preterm infant, but increase with increasing gestational and postnatal age. Moreover, both the viscosity (Fahraeus-Lindqvist effect) and the hematocrit reductions (Fahraeus effect) in narrow tubes are more pronounced in the fetus and neonate than in adults. As a result of these peculiar hemorheological properties, viscosity of blood (measured in 50 mu m diameter tubes) with given hematocrit is markedly lower in the fetus (-50% at 25 wk gestation) and neonate (-25%) than in adults. Blood viscosity in 50-mu m tubes is similar in neonates with a hematocrit of 0.70 l/l as in adults with a hematocrit of 0.50 l/l. This may explain why polycythemia does not impair systemic, cerebral and intestinal RBC transport in neonates as long as the hematocrit does not exceed 0.70 l/l and why polycythemic neonates are less susceptible to serious complications than polycythemic children and adults.Pathological Hemorheology: Since high flow conditions in the fetus and neonate are strongly dependent on the favorable theologic properties of their blood, hemorheolocal abnormalities may contribute to the high risk of the fetus and neonate to ischemic damage of vital organs (e.g. brain) in a variety of disorders: 1) Perinatal asphyxia may be associated with impaired RBC deformability, increased RBC aggregation and leukocyte count, thereby aggravating tissue hypoxia. 2) In growth-retarded fetuses, increased hematocrit, RBC aggregation and leukocyte count may contribute to the high risk of ischemic damage of vital organs (e.g. brain). 3) Fetal and neonatal cells are less protected from radicals than adults, thereby predisposing them to oxidative damage. 4) Neonatal septic shock may be associated with markedly decreased RBC deformability, increase in the count of rigid, immature leukocytes, RBC aggregation and plasma viscosity. 5) Infants of poorly-controlled insulin-dependent diabetic mothers show markedly increased hematocrit and decreased RBC deformability. This may increase their risk of thromboses.
Erythrocyte membrane lipids, ATPase activities, blood cell parameters and hemorheological changes were measured in 51 patients with acute cerebral infarction, 12 patients with arteriosclerosis and 51 normal controls. A decrease in erythrocyte deformability, ATPase activities and an increase in CHO/PL ratio and viscosity at high shear rate were observed in stroke patients in which a significant difference was found compared with that of the control group, Multivariate regression analysis indicated that membrane lipids, ATPase activities, CHO/PL ratio viscosity at high shear rate had linear correlation with erythrocyte deformability. The coefficient of multiple correlation was 0.8937.These findings suggested that the erythrocyte membrane lipid composition and ATPase activities change significantly in stroke patients. These may be the cause of hemorheological disturbance. These changes existed before the occurrence of the stroke. So it is important to treat the circulation disorder in arteriosclerosis patients to prevent the cerebral infarction. The adoption of treatment with drugs for improving microcirculation and ion transport may be of benefit in the recovery from a stroke. We concluded from our study that CHO/PL could be a feature of arteriosclerosis or strokes, and ATPase activities may serve as an early indication of the patient's state.
Platelet membrane fluidity, platelet membrane cholesterol/phospholipid ratio, platelet membrane individual phospholipids and plasma Lipid composition were evaluated in diabetics, in subjects with vascular atherosclerotic disease (VAD), in VAD subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in hypertensives. The platelet membrane fluidity did not distinguish normals from diabetics and normals from hypertensives; this microrheological parameter discriminated instead normals from VAD subjects and normals from VAD subjects with NIDDM. Platelet membrane cholesterol/phospholipid ratio discriminated normals from hypertensives only. Of the platelet membrane individual phospholipids, while the phosphatidylcholine (PC) was increased, the phosphatidylserine (PS) was reduced in diabetics; no significant difference was evident between normals and VAD subjects with and without NIDDM, while in hypertensives the PC was significantly increased. In each group of patients the study of correlations between platelet membrane fluidity and platelet membrane Lipid pattern, as well as that between platelet membrane fluidity and plasma lipid composition, shows contrasting results.
