Clinical Hemorheology and Microcirculation

Thromboembolic complications remain an important cause of maternal mortality. The present recommendations favour for prophylaxis unfractionated (UFH) and low molecular weight heparin (LMWH). We investigated 150 pregnant women before and after cesarean section in three randomized groups. Fifty women received no prophylaxis (group I), 50 women UFH two times 5000 IU/day (group III) and 50 women Dalteparin 5000 U/day (group II). We determined the blood count, the rheological parameters and cholesterol, triglycerides, D-dimer, fibrinogen and the anti-Xa-level. We found a classical hemodilution, with increase of erythrocyte aggregation and plasma viscosity postoperatively. The fibrinogen turnover and D-dimer concentration were elevated. The patients with Dalteparin prophylaxis showed lower thrombin activation, minor changes in the cholesterol and triglycerides level and an improvement of red cell deformability in low shear regions. Our results demonstrated an influence of Dalteparin on the rheological parameters post surgery. The DVT incidence was 1.33% generally and occurred only in the Control group and in women with unfractionated heparin. We observed no side effects such as major bleeding, osteopenia or allergy.

Erythrocyte deformability (ED) has been scarcely evaluated in obese patients without other concomitant cardiovascular risk factors and contradictory results have been published regarding the influence of plasma lipids on the erythrocyte membrane lipid composition and insulin resistance on this rheological parameter. In 67 severe or morbid obese patients without other cardiovascular risk factors (51 women and 11 men, aged 34±11 years) and in 67 controls (45 women and 22 men, aged 32±10 years), ED has been determined by ektacytometric techniques in a Rheodyn SSD, the elongation index (EI) being measured at 12, 30 and 60 Pa, along with plasma lipids, red blood cell membrane lipids (cholesterol and phospholipids) and insulin resistance indexes in basal conditions and after a three month diet period. No significant differences were obtained in the EI between obese patients and the control group at any of the shear stresses tested (P>0.05). The cholesterol and phospholipid content of the red blood cell membrane did not significantly differ between cases and controls (P>0.05). Obese patients with metabolic syndrome showed lower EI at 30 and 60 Pa than those without metabolic syndrome (P=0.014 and P=0.031 respectively). Weight loss was not accompanied by any changes in these rheological parameters. Obesity itself does not seem to modify ED. However, metabolic syndrome seems to decrease ED, possibly through insulin resistance.

Background: Microvascular involvements represent one of the first steps in many autoimmune diseases such as rheumatoid arthritis (RA). The aim of this study was to investigate the differences in periodontal microcirculation between healthy subjects and patients suffering from RA. Methods: Thirty healthy subjects and 30 patients suffering from RA were examined. The patients who showed conditions known to compromise microcirculation, such as diabetes, hypertension, pharmacological treatments, were not included in the group of healthy patients. All the patients were non-smokers. Periodontal capillaroscopy was used to investigate the characteristics of microcirculation. Visibility, course, tortuosity, as well as the possible presence of microhemorrhages, the average caliber of the capillary loops and the number of visible capillary loops per square millimeter were evaluated for each patient. Results: Microcirculation architecture in the healthy and in the RA patients was characterized by a network of capillaries in polygonal mesh with parallel orientation as regards the surface. In patients suffering from RA, it was possible to observe a reduced caliber of capillaries, as well as a greater number and elongated capillaries. No significant differences relating to oral capillaroscopic pattern were detected between RA patients that were rheumatoid factor, ANA, RANA positive and RA patients that were rheumatoid factor, ANA, RANA negative. Conclusions: This study shows that capillary alterations in patients suffering from RA occur in periodontal microcirculation; such evidence could be extremely important, suggesting that microvascular periodontal alterations may play a crucial part in the complex activity associated with periodontal disease in AR patients.

The rheologic properties of red blood cells (RBC) are determined by humoral and cellular factors. Fatty acid composition of the RBC phospholipid bilayer is one factor influencing membrane fluidity this could affect RBC aggregation because of a higher bias of RBC deformability. The present investigation was performed to investigate a possible relationship between fatty acid composition and erythrocyte aggregation using animals with high RBC aggregation (horse and pig) and animals with immeasurable RBC aggregation (sheep). Horse and pig showed similar distribution of the four major components palmitoleic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), and linoleic acid (C18:2n6). The sheep's saturated fatty acids C16:0 and C18:0 were decreased, whereas unsaturated oleic acid (C18:1n9) showed a two fold increase in comparison to horse and pig. It can be assumed that the fatty acid bilayer is a minor factor influencing erythrocyte flexibility due to its influence on membrane fluidity and therefore there might be an existing link to erythrocyte aggregation. The sheep has relatively dense erythrocytes with low cell volumes. Therefore, the absence of aggregation might be postulated to arise from geometric factors against the expected effect of unsaturated fatty acids on membrane fluidity, the higher level of unsaturated fatty acids in ovine erythrocytes over that found in horse and pig was surprising. The present result, which accords with former studies, indicates that the geometric factor given by the intracellular skeleton overrides any effect of membrane composition on aggregation in sheep.

During acute exercise several significant cardiovascular alterations take place, along with possible physiopathological consequences, such as Exercise Inducted Pulmonary Haemorrhage (EIPH). Given the relevance of blood rheology in the determination of flow resistance and its supposed participation in the stated events, the present paper focuses on the analysis of modifications in haematocrit, blood viscosity and erythrocyte deformability in Thoroughbred horses caused by two different levels of effort (6 to 9 m/s and 13 to 16 m/s), in the same track they train in and with their own jockeys. The results obtained show a deep modification in those parameters, as consequence of the exercise. However, no significant discrepancies were observed between the different levels of effort in which the training was performed.

It has been shown that weight loss and physical activity contribute to a better biorheological profile. Yet, the concentrations of fibrinogen are not always reduced following life style modification. We evaluated the inter-relations between fibrinogen's pro red cell aggregation potential and reduced inflammation and improved lipid profile as anti-aggregating forces in a group of 20 apparently healthy obese volunteers following 4 and 8 months of intensive life modification program which included diet and strenuous physical activity. A significant (p=0.005) weight loss (from a mean±SD of 121.4±20.9 to 98.0±21.3 kg) and decrease in body mass index (from 40.8±4.3 to 32.9±5.3 kg/m², p=0.005) was noted in fourteen individuals who completed the 8-month program. The concentrations of clottable fibrinogen rose from 318±96 to 387±72 mg/dl (p=0.012) while there was a significant reduction in the erythrocyte sedimentation rate (ESR) (from 19.0±12.6 to 10.8±7.5 mm/h, p=0.018), triglycerides (from 143±80 to 80±44 mg/dl, p=0.005), LDL cholesterol (from 128±34 to 103±17 mg/dl, p=0.005) and total cholesterol (from 211±40 to 171±17 mg/dl, p=0.007), as well as decrease in insulin concentration (from 36.1±21.3 to 20.6±8.0 μu/ml, p=0.01) and the insulin resistance index (HOMA-R, from 9.1±6.4 to 4.9±2.1 glu*ins/405, p=0.008). Despite a significant increment in the concentrations of clottable fibrinogen, a significant reduction was noted in the degree of red cell aggregation as measured by using a slide test and direct visualization of the aggregates. Our conclusion is that the pro-aggregating properties of fibrinogen following intense physical activity are probable counterbalanced by the anti-aggregatory properties of an improved lipid profile and an attenuated acute phase response.

It is not clearly established whether reticulocyte deformability is lower than that of the mature erythrocytes, as most of studies published on this matter have evaluated this rheological parameter by means of micropipette techniques, which are unsuitable for routine measurements. Information is scarce as regards the evaluation of reticulocyte deformability by means of ektacytometry techniques, routinely used in clinical laboratories. We aimed to evaluate erythrocyte deformability (ED), with ektacytometry, in samples of 44 anaemic patients with peripheral reticulocytosis (reticulocytes: (260±150)×10³/μl) and in 60 healthy non-anaemic volunteers with a normal reticulocyte count (reticulocytes: (60±20)×10³/μl). We also determined other factors that may influence ED, such as erythrocyte indices (MCV, MCH, MCHC), glucose, total cholesterol and triglycerides. ED was evaluated determining the elongation indices (EI) at 12, 30 and 60 Pa, by means of the Rheodyn SSD. At the three shear stresses tested, patients showed statistically lower EI than controls, higher reticulocyte count, lower cholesterol levels and higher MCHC (P<0.001, respectively). A statistically significant negative correlation (P<0.01) was found between the reticulocyte count and the EI at 12, 30 and 60 Pa (r=−0.643, r=−0.678 and r=−0.692, respectively), and between the EI and the MCHC (correlation coefficients: −0.743, −0.741 and −0.738; P<0.01). As the differences in ED could be attributed partly to alterations in erythrocyte indices and plasma lipid levels, a linear regression analysis was performed, showing that EI is independently associated with the reticulocyte count. Our results suggest that reticulocytes are responsible for the decreased ED observed in anaemic patients with peripheral reticulocytosis, when this hemorheological parameter is evaluated by means of ektacytometry techniques.

The relationship among the nitric oxide synthase (NOS) inhibitor [asymmetric dimethylarginine (ADMA)], NOS cofactor [tetrahydrobiopterin (BH₄)], and superoxide anion in the patients with acute myocardial infarction (AMI) is still unknown. This study sought to assess the NOS inhibitor and cofactor with oxidative stress in AMI patients (n=9) during initial administration and 4 weeks after medical treatments. We measured plasma NOS inhibitor and cofactor (ADMA and BH₄) by HPLC and plasma oxidized-LDL by ELISA. Blood samples from age-matched healthy volunteers (n=9) were taken for comparison. In AMI, plasma ADMA, oxidized-BH₄ (BH₂+biopterin) and oxidized-LDL significantly increased (P<0.0001, P<0.01 and P<0.05 vs. healthy volunteers) and plasma BH₄, plasma nitrate and L-arginine/ADMA significantly decreased compared with healthy volunteers (P<0.0001, P<0.05 and P<0.005 vs. healthy volunteers). Medical treatments improved plasma ADMA, nitrate, BH₄ and oxidized-LDL. In conclusion, ADMA increased, and NO and BH₄ decreased with oxidative stress in AMI, and these mediators improved in AMI patients with medical treatments. These findings indicated that inhibition of NOS with oxidative stress plays a crucial role in endothelial dysfunction in patients with AMI.

Pain intensity in chronic venous disease varies with the stage in the clinical-etiologic-anatomic-pathophysiologic (CEAP) classification but also with patient perception, pain being by definition subjective. The venous hypertension responsible for the varicose veins and trophic changes in CVD has a variety of algogenic repercussions in which leukocytes play a particular role, notably through their ability to roll along the vessel wall. Shear stress, hypoxia and stasis activate the marginated leukocytes to shed L-selectin from their surface and express integrins, matrix metalloproteinase 9, elastase, lactoferrin and free radicals. Meanwhile the endothelium expresses adhesion molecules that permit slow rolling on E-selectin followed by adhesion and tissue transmigration. Vein wall and valve areas in particular attract mast cells, monocyte-macrophages and T lymphocytes, and undergo remodeling. Sympathetic sensory C and Aδ fibers, which wrap around cutaneous venules and are also present in the venous intima and media, are nociceptors sensitive to the pain mediators concentrated within leukocytes, such as mast cell bradykinin, responsible for visceral pain. Neuronal inflammation combined with wall remodeling intensifies symptoms. Yet no direct link has so far been shown between pain and mast cell mediator levels. Leukocyte adhesion is also associated with the increased capillary permeability that leads to edema. Antileukocyte therapies include postural rest and venotonics which alone or in combination with compression have been shown to unstick and inhibit leukocytes. The micronized purified flavonoid fraction (MPFF) protects vascular endothelium against hypoxia and reduces adhesion molecule expression. Unlike other antileukocyte therapies, venotonics do not cause neutropenia.