Clinical Hemorheology and Microcirculation

The hemorheological parameters, erythrocyte aggregation and deformability are determined in jaundice patients and are compared with that of healthy subjects. The aggregation process is determined by sequential analysis of the He-Ne laser transmission data after passing through erythrocyte suspension at hematocrit 5%. The analysed data is represented by aggregation parameters-aggregate size index, aggregate sedimentation time index, total number of fluctuations, time required for completion of process, effective number of cells and effective cellular sedimentation duration. The erythrocyte deformability is determined by measurement of passage time (reciprocal of deformability) of erythrocyte suspension in phosphate buffered saline at hematocrit 6% through cellulose membranes. The observations show that the aggregation process in jaundice starts earlier, form compact structures which move faster initially and thus reducing the effective number of cells in the observation volume at all time intervals compared to that of normal suspensions. The application of inhomogeneous magnetic field to erythrocyte suspension produces significant effect in total number of fluctuations in normals whereas no such change is observed in jaundice patients. The deformability of the cells is decreased. A combination of these alterations in erythrocyte deformability and aggregation may contribute to increase blood viscosity.

Aggregation process of erythrocytes in mammals is determined. This process is described in terms of parameters which are determined by sequential recording and analysis of the He-Ne laser light transmission data after passing through erythrocyte suspension at hematocrit 5%. These parameters provide information on variation in aggregate size, sedimentation time, total number of fluctuations due to formed aggregates and process completion time. The analysis shows that in horse blood samples the formation of a large number of aggregates is significantly faster compared to that in human and buffalo samples. Their mobility as determined by sedimentation time also shows a similar pattern. The erythrocyte suspensions of cow, goat and rabbit do not show any fluctuation which indicates that these cells remain in monodisperse state over a long duration. The time taken for clearance of observation volume is the maximum for goat (10.6 hr) and minimum for horse (8.1 min).

Impaired retinal blood flow may be involved in the development of retinopathy of prematurity (ROP). We investigated hemorheological parameters in 44 premature infants (birth weight 610 to 2010 g, gestational age 25 to 34 weeks) at a postnatal age of 6 weeks. 25 infants showed no evidence of ROP and 7 developed ROP stage I (group' A: no-or-mild ROP, n = 32). Five infants developed ROP stage II and 7 ROP stage III (group B: moderate to severe ROP, n = 12). Plasma viscosity increased with increasing ROP severity and was significantly higher in group B than in group A (1.19 ± 0.06 vs. 1.00 ± 0.02 mPas; p = 0.0005, mean ± SEM). Plasma IgM was higher in group B patients (0.58 ± 0.08 vs. 0.47 ± 0.03 gil; p = 0.016) and RBC aggregation index was slightly increased in group B when compared to group A (6.33 ± 1.17 vs. 5.40 ± 0.49; P = 0.055). These data suggest that elevated plasma viscosity and RBC aggregation may be involved in the development of ROP.

We examined 43 women with stage II breast cancer receiving adjuvant Epirubicin / Cyclophosphamid chemotherapy. Preoperatively and before each of six cycles of chemotherapy erythrocyte aggregation (stasis and low shear), plasma viscosity, hematocrit, platelets, leukocytes and fibrinogen levels were estimated and impedance plethysmography (IPG) was performed for screening of deep vein thrombosis (DVT). We observed 5 DVT (11.6 %) during chemotherapy. These patients were significantly older than patients without DVT. Preoperatively, all cancer patients demonstrated a hyperviscosity state which was most pronounced in DVT patients and characterized by a significantly elevated plasma viscosity, erythrocyteaggregation and fibrinogen levels. Mean fibrinogen levels were significant correlated with plasma viscosity in all cancer patients (r = 0.38; p < 0.0001). Platelets, leukocytes as well as hematocrit showed no pathologic changes in cancer patients and did not contribute to the hyperviscosity state. Throughout chemotherapy only fibrinogen levels showed a further significant increase versus patients without DVT. Although preoperative erythrocyte aggregation offered the best prediction (specitivity: stasis 92 %, low shear 97 %; neg. prediction: 92 % respectively 90%) from all estimated rheological parameters-for later DVT the clinical importance is of limited value. All DVTs were detected by IPG and a normal result excluded DVT in 100 % of the cases.

The aim of this study was to verify if abnormalities of sodium content can explain the decrease in the red blood cell deformability observed in diabetic patients.

Erythrocyte deformability based on filtration index, membrane chemical composition evaluated by free cholesterol, phospholipid fractions measured by thin layer chromatography, total protein, sodium, potassium and magnesium contents were investigated in 37 non insulin dependent diabetic (NIDD) patients and 26 control subjects.

The results showed that erythrocyte sodium content was higher in diabetic patients than in controls and it correlated significantly with filtration index and membrane lipid contents.

The aim of the present study was to investigate the hemorheological effects of captopril and isosorbide dinitrate (ISDN) in patients with chronic congestive heart failure (CHF) due to coronary heart disease (CHD). 51 patients were enrolled in this double–blind, randomised, comparative trial. All patients had a left ventricular ejection fraction of less than 40% corresponding to NYHA-class II or III, and were on a baseline regimen with diuretics. During the 3-week run-in phase, treatment with captopril was initiated up to a daily dosage of 2×25 mg. Then all patients were randomised to receive either ISDN (2×40 mg/day) or placebo over a 16-weeks double-blind phase.

We were able to demonstrate a significant decrease of plasma viscosity (p < 0.05) and white blood cell count (p < 0.01) during treatment with captopril. The additional treatment with ISDN did not lead to further changes in the hemorheological profile.

In conclusion, ACE-inhibition with captopril leads to a moderate improvement of blood rheology in patients with CHF due to CHD. Nitrates added to a baseline treatment with captopril and diuretics do not further improve blood rheology. This may be explained by the pronounced vasodilatory effect of captopril due to inhibition of angiotensin II and increased levels of bradykinin.

The primary cardiac defect in Congestive Cardiac Failure (CCF) is decrease in intrinsic contractility of myocardium, usually brought on by prolonged pressureandl or volume overload. A wide range of factors may precipitate or aggravate or worsen blood flow conditions leading to the cardiac failure, and hemorheological factors could be one of them. This investigation aimed to study the possible role and association between change in hemorheological parameters and congestive cardiac failure. Parameters studied in this study on 88 patients of congestive cardiac faliure were - whole blood viscosity, plasma viscosity, red cell rigidity, hematocrit, erythrocyte sedimentation rate, fibrinogen, cholesterol, triglycerides and albumin. The patients were categorized in to 2 subgroups on the basis of their clinical history and diagnosis. The first group was, congestive cardiac failure with coronary heart disease and second group congestive cardiac failure with hypertension. There were significant changes in the hemorheological parameters in both the groups. In cases of congestive cardiac failure with coronary heart disease rise in blood viscosity at low shear rate (p<0.0001) was more significant as compared to high shear rate (p<0.01). Increases in plasma viscosity, red cell rigidity, fibrinogen and erythrocyte sedimentation rate were very significant. Among biochemical parameters increase in plasma triglycerides was statistically significant (p<0.01). In the second group, congestive cardiac failure with hypertension, showed marked increase in whole blood viscosity at low and high shear rates. In this group increase in red cell rigidity was most significant as (p<0.0001) compared to other parameters. Increase in plasma viscosity, fibrinogen and plasma cholesterol & triglycerides were also significant. It was found that the regular smokers had higher values of blood viscosity, red cell rigidity (p<0.05), hematocrit (p<0.005) and plasma viscosity (p<0.05) as compared to non-smoker patients in both the groups. There was no significant change in albumin and hematocrit in both the groups as compared to normal controls. The present study highlights the possible role of hemorheological factors along with other physiological factors in congestive cardiac failure.

The effect of a commercially available human immunoglobulin G—Sandoglobulin ^R—on the rheological properties was quantitatively examined in 51 pregnant women with a history of two or more spontaneous abortions. The in vivo effects were assessed during 5 courses of treatment with 150 g, 102 g and 66 g immunoglobulin, respectively.

We could not demonstrate a significant effect after IVIG on erythrocyte aggregation, plasma fibrinogen and hematocrit. The dose dependent changes in plasma viscosity that occur after IVIG therapy are compensated by hemodilution.

Ischaemic heart disease and its various clinical manifestations, whether acute or chronic, are shown to be characterized by hyperviscosity syndrome, more evident in the acute than in the chronic phase. In the present study the effect of i.v. Streptokinase (SK) treatment in 13 patients affected by AMI was evaluted; the haemorheological parameters (blood and plasma viscosity, blood filterability, fibrinogen and haematocrit) were measured in basal conditions, at the end of the infusion and 24 hours later. The patients showed high blood and plasma viscosity and low blood filterability in basal conditions. A decrease of blood and plasma viscosity with reduction of fibrinogen was observed at the end of the infusion, associated with an improvement in blood filterability. After 24 hours the haemorheological parameters showed a trend towards basal values without reaching them. On the contrary, 13 patients with AMI who could not undertake SK treatment showed an increase of blood and plasma viscosity and a reduction of blood filterability at the 8th hour lasting until the 24th hour. The haemorheological improvement observed in patients treated with SK may be correlated to the fibrinogenolytic activity of the drug; the results of the present study support the hypothesis that SK may be a useful tool in AMI manegement.