Investigation of hemorheological parameters in periodontal diseases.

Periodontal diseases are frequently associated with cardiovascular diseases (CVD). On the other hand, occurrence of CVD has also been related with increased blood viscosity. This study was planned to investigate four main hemorheological parameters contributing to blood viscosity - hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity - and also some biochemical parameters (hs-CRP, fibrinogen, globulin etc.) in patients with periodontal disease. We hypothesized that poor periodontal health would be associated with deterioration of hemorheological properties. According to periodontal health status, subjects were divided into three groups as control (healthy), with plaque induced gingivitis and with chronic periodontitis. All groups included 15 males who had not received periodontal therapy in the last six months before the study, were non-smokers, had no systemic diseases and were not on any medication. Erythrocyte deformability and erythrocyte aggregation were measured with laser-assisted optical rotational cell analyzer (LORCA). Plasma viscosity was measured by a cone-plate viscometer. Data were analyzed with Kruskal-Wallis, Mann-Whitney U Test and Spearman Correlation Coefficient. Plasma viscosity (1.36 ± 0.01 mPa.s in the control group and 1.43 ± 0.02 mPa.s in the chronic periodontitis group, P <  0.01), erythrocyte aggregation tendency (aggregation index, amplitude and t½ were 58.82 ± 1.78% , 20.22 ± 0.40 au, 2.80 ± 0.25 s respectively in the control group, and 67.05 ± 1.47% , 22.19 ± 0.50 au, 1.84 ± 0.15 s in the chronic periodontitis group, P <  0.01), hs-CRP, fibrinogen and globulin levels were significantly higher, whereas HDL level was significantly lower in the chronic periodontitis group (P <  0.05) compared to the control group. All of these conditions may contribute to cardiovascular morbidity and mortality observed in people with periodontal disease, via increasing blood viscosity.

Relationship between hemorheology and endothelial dysfunction in renal transplant patients receiving calcineurin inhibitors.

BACKGROUND: Calcineurin inhibitors, mainly cyclosporin A (CsA), are associated with endothelial dysfunction in renal transplant recipients (RTRs). Hemorheological disturbances including decreased erythrocyte deformability (ED), increased plasma viscosity and erythrocyte aggregation (EA) have also been reported in CsA-treated RTRs. The aim of this study was to investigate the relationship between hemorheological factors and endothelial dysfunction in CsA- and tacrolimus (Tc)-treated RTRs. METHODS: Thirty-one RTRs and 16 healthy subjects were recruited. The RTR group received either CsA (n = 16) or Tc (n = 15). Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. ED and EA were measured with laser-assisted optical rotational cell analyzer, and plasma viscosity by a cone-plate viscometer. RESULTS: FMD of the CsA group was significantly lower than that of controls (6.3% ± 5.1% vs. 11.9% ± 5.6%, p = 0.024), whereas, there was no significant difference between the Tc group (8.8% ± 5.4%) and controls. At shear stresses ranging between 0.95 and 30 Pa, EDs of the CsA group were significantly lower compared with controls. In the Tc group, the decrease in ED was significant at shear stresses ranging between 0.53 and 5.33 Pa. ED indices did not correlate with FMD in any of the groups. CONCLUSIONS: The degree of endothelial dysfunction and reduction in ED were more remarkable in patients on CsA therapy. Hemorheological factors were not likely to be associated with endothelial dysfunction in RTRs.

Hemorheological changes with strontium ranelate treatment do not seem to be related to its claimed prothrombotic effects.

Strontium ranelate is claimed to be related with increased risk of thromboembolic events. No explanation of this increased incidence of thromboembolism has been identified. However, growing evidence has clearly demonstrated the involvement of blood rheology in any thrombotic process. The aim of this study was to assess hemorheological changes with strontium ranelate treatment in elderly women with osteoporosis. This study was designed in a prospective manner. Twenty-two elderly women diagnosed with osteoporosis were included. During a 2-month treatment period, participants received strontium ranelate 2g/day. Hemorheological parameters including erythrocyte deformability, erythrocyte aggregation and plasma viscosity were measured before and after 2 months therapy with strontium ranelate. The median age of the patients was 70.0 (range=65-80) years. After 60 days of treatment, there was no statistically significant change in hemorheological parameters. None of the subjects developed clinical venous thromboembolic event (VTE) during the 2-month period of strontium ranelate treatment. Our study demonstrated that in elderly women, treatment of osteoporosis with strontium ranelate did not change hemorheological parameters over 2 months of time. However, its long-term effects on hemorheologic parameters should be evaluated further with a larger sample.

Blood viscosity changes in slow coronary flow patients.

Microvascular dysfunction is implicated in the pathogenesis of slow coronary flow (SCF), but less attention has been paid to intrinsic properties of blood that can also impair the microcirculatory flow. In this study we aimed to evaluate the blood viscosity focusing on erythrocyte aggregation, erythrocyte deformability and plasma viscosity in SCF. Thirty-three patients with SCF (21 male, 54 ± 12.8 years) and 23 subjects with normal coronary arteries (13 male, 59 ± 10.3 years) were included in the study. Coronary flow was quantified by means of thrombolysis in myocardial infarction (TIMI) frame count and aggregation and deformability of erythrocytes were measured by an ektacytometer. Plasma viscosity was measured by a cone-plate viscometer. Aggregation amplitude (23 ± 3.8 au vs. 15.7 ± 6.1 au, respectively, p < 0.001) and area A index (area above syllectogram) (153.2 ± 30.7 au.s vs. 124.9 ± 49.3 au.s, respectively, p < 0.01) were higher in SCF patients. Aggregation half-time, aggregation index, elongation index and plasma viscosity values were similar between two groups. Correlation analysis revealed a significant relationship between the TIMI frame count for left anterior descending artery and aggregation amplitude in SCF patients (r = 0.679, p < 0.0001). The result of this study reveals changes in erythrocyte aggregation which may contribute to the pathophysiology of SCF. Larger studies are needed to make more robust conclusions on this issue.

Effects of oral acrylamide intake on blood viscosity parameters in rats.

Acrylamide which is formed via reaction of reducing sugars with amino acids during food processing at high temperatures is not only neurotoxic and carcinogenic, but it also damages erythrocyte membrane and generates micronucleated erythrocytes. In the present study, effects of chronic administration of acrylamide at a dose which does not induce neurotoxicity were evaluated on blood viscosity parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity). Twenty adult male Sprague-Dawley rats were divided into control and acrylamide groups. The acrylamide group received 10 mg/kg/day acrylamide, whereas the control group received saline (vehicle), both in 10 ml/kg/day volume via gastric gavage. Erythrocyte aggregation and deformability were measured with LORCA and plasma viscosity with cone-plate viscometer. Erythrocyte deformability was measured before, and at the end of the 3rd and the 5th weeks of acrylamide administration. Hematocrit, erythrocyte aggregation and plasma viscosity were measured only at the end of the 5th week. Acrylamide caused a significant decrease in the deformability index of erythrocytes (at the end of the 3rd week, control: 0.606 ± 0.003, acrylamide: 0.595 ± 0.003, p < 0.05) (at the end of the 5th week, control: 0.606 ± 0.002, acrylamide: 0.588 ± 0.002, p < 0.01). Aggregation tendency and plasma viscosity were slightly higher in the acrylamide group, however the difference was not statistically significant. These results imply that acrylamide which does not cause neurotoxicity in rats may alter blood viscosity if chronically taken.

Functional effects of endothelial nitric oxide synthase genetic polymorphisms on haemorheological parameters in healthy human individuals.

The constitutive endothelial nitric oxide synthase (eNOS) plays a major role in circulatory homoeostasis and shows genetic polymorphism. eNOS is expressed and functional in blood cells, including erythrocytes. There is limited knowledge about the consequences of eNOS genetic variability in haemorheological parameters and erythrocyte functioning. The purpose of this study was to investigate the effects of three eNOS genetic polymorphisms, namely exonic G894T (Glu298Asp), intronic VNTR (27-bp repeat) and 5'-flanking T(-786)C polymorphisms on haemorheological variables, such as erythrocyte deformability and erythrocyte aggregation (rouleaux formation) in healthy non-smoking volunteers. Sixty subjects (19 women, 41 men) were examined for genotypes and haemorheological variables. Genotypes were determined by polymerase chain reaction and restriction analysis. Haemorheological variables were measured by means of a laser-assisted optical rotational cell analyser (LORCA). Erythrocyte aggregation was significantly decreased in individuals with 894TT genotype when compared to subjects with the (G) allele. Aggregation indices (AI) were 54.7±3.2% versus 61.0±0.9% (p=0.026), and the half-lives (t(1/2) ) for aggregation formation were 3.43±0.43 versus 2.55±0.12 sec. (p=0.024), respectively. Similarly, VNTR-bb genotype significantly altered erythrocyte aggregability. AI values were 58.7±1.1% in subjects with VNTR-a allele versus 63.7±1.2% in subjects with bb genotype (p=0.011); t(1/2) values were 2.86±0.16 versus 2.20±0.13 sec., respectively (p=0.016). T(-786)C polymorphism did not change any haemorheological parameters. These findings suggest that eNOS 894TT genotype is associated with decreased erythrocyte aggregation, while VNTR-bb genotype increases aggregability in healthy human individuals. eNOS genetic variants may contribute in the pathogenesis of microvascular disorders by altering erythrocyte functions in human beings.

The association of ocular blood flow with haemorheological parameters in primary open-angle and exfoliative glaucoma.

PURPOSE: To evaluate the ocular blood flow velocities and haemorheological parameters in patients with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG) and exfoliation syndrome (XFS) and to compare their results with those of healthy controls. METHODS: Twenty-five patients with POAG (group 1), 25 patients with XFG (group 2), 25 patients with XFS (group 3) and 25 healthy controls (group 4) were included in the study. Ocular blood flow velocities of ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs) were measured using colour Doppler imaging (CDI). Haemorheological parameters (erythrocyte elongation and aggregation index, aggregation amplitude, aggregation half-life, plasma viscosity, haematocrit) were measured in venous blood samples of all patients. RESULTS: The peak systolic velocity (PSV) and end-diastolic velocity (EDV) values were lower and resistive indices (RI) were higher for the OA, CRA and SPCA of glaucomatous (groups 1 and 2) patients compared with those of controls (group 4) (PSV: OA, 40.4 ± 11.3 versus 52.6 ± 12.8 cm/second, p < 0.001; CRA, 12.9 ± 2.9 versus 15.3 ± 4.2 cm/second, p = 0.02; SPCA, 21.7 ± 6.6 versus 26.6 ± 8.3 cm/second, p = 0.013) (EDV: OA, 10.3 ± 4.3 versus 14.2 ± 5.1 cm/second, p < 0.001; CRA, 3.7 ± 1.1 versus 4.5 ± 1.3 cm/second, p = 0.025; SPCA, 5.2 ± 1.8 versus 7.7 ± 3.2 cm/second, p = 0.001) (RI: OA, 0.75 ± 0.05 versus 0.66 ± 0.07, p < 0.001; CRA, 0.73 ± 0.08 versus 0.68 ± 0.10, p = 0.223; SPCA, 0.70 ± 0.10 versus 0.63 ± 0.11, p = 0.004). There were no statistically significant differences between the haemorheological parameters of glaucomatous and non-glaucomatous patients. The reduction in ocular blood flow velocities in groups 1, 2 and 3 were not associated with changes in haemorheological parameters. CONCLUSION: Our results suggest that impairment of the retrobulbar blood flow in POAG and XFG is not associated with alterations in haemorheological parameters.

Effects of pravastatin on cellular ultrastructure and hemorheology in rats after traumatic head injury.

Pravastatin has neuroprotective effects against aging but its role in brain injury remains unclear. This study evaluated the effects of pravastatin on the ultrastructural changes and hemorheological parameters in rats after traumatic brain injury (TBI) of right parietal cortical contusion by a controlled weight-dropping method. There were three groups: (I) Sham operated group; (II) TBI + vehicle (saline) group; and (III) TBI + pravastatin group. Right parietal craniectomy was performed in all groups. In TBI + pravastatin group, pravastatin was administered orally at a dose of 1 mg/kg every day for 7 days starting at 24 hours after the injury. Plasma viscosity, erythrocyte deformability and erythrocyte aggregation were measured from blood samples of all rats on 2nd, 7th and 15th days. At the same time electron microscopic study was done on designated days for groups II and III. Treatment with pravastatin markedly increased aggregation amplitude and γIsc max values and significantly decreased erythrocyte deformability but did not change plasma viscosity in 2 weeks time. Ultrastructural parameters such as perinuclear edema, mitochondrial swelling and intraneuronal vacuoles were detected in lower degree in the statin group when compared to the saline group, especially decreased demyelinization and endothelial detachment was prominent. As a result, the hyperviscosity state with increased erythrocyte aggregation and decreased erythrocyte deformability induced by pravastatin in this study was accompanied by an improvement of the ultrastructural findings in TBI. This hyperviscosity state may be a compensatory mechanism to increase the oxygenation of the injured tissue by inducing the release of antiaggregant and vasodilatory substances by increasing shear stress. Therefore, we suggest that prolonged pravastatin usage may exert affirmative effects on traumatic brain injury conditions by increasing blood viscosity.

Reduced erythrocyte deformability in active and untreated Behçet's disease patients.

OBJECTIVE: Although the etiology of Behcet's disease is not clarified yet, the vascular endothelial damage and thrombosis are prominent features of the disease. The underlying mechanisms of increased risk of thrombosis in Behcet's disease are not completely understood. It is stated that the changes in blood rheology such as erythrocyte deformability take part in the thrombosis. There are limited numbers of studies with conflicting results about the erythrocyte deformability in Behcet's disease. The previous studies were not limited to the untreated patients with active disease. METHOD: Blood samples were filtered immediately by "Imugard- leukocyte removal filter". After plasma and erythrocytes were separated by centrifugation, 10% erythrocyte suspensions were prepared with isotonic Tris NaCl buffer solution. These erythrocyte suspensions were filtered under gravitational force by "Nucleopore" to determine the filtration time. The filtration times of the erythrocyte and buffer solutions were referred as t1 and t2 respectively. Finally, deformability indices were obtained by dividing the t1 by t2. A decrease in the deformability of the erythrocytes would result in an increase in the filtration time of the erythrocyte suspension and deformability indices. RESULTS: The median deformability indices were 3.090 and 2.170 for patients and control subjects respectively and the difference was statistically significant (P = 0.000). CONCLUSION: We suggest that the decrease in erythrocyte deformability in Behcet's disease may be related to oxidative damage of erythrocytes and subsequently takes part in the development of thrombosis in Behcet's disease.

Melatonin prevents lipid peroxidation in human erythrocytes but augments deterioration of deformability after in vitro oxidative stress.

Oxidative stress decreases the deformability of erythrocytes. Anti-oxidant measures may alleviate, pro-oxidative damage may augment this decrease. Melatonin is reported to exert both anti-oxidant and pro-oxidant properties on erythrocytes. The aim of the present study was to evaluate the effects of melatonin on erythrocyte deformability under oxidative stress conditions induced by the combination of hydrogen peroxide (20 mM) and sodium azide (100 microM). Erythrocyte suspensions were incubated for 10 min with melatonin (1-1000 microM) prior to oxidative stress. Erythrocyte deformability was measured by Laser-assisted Optical Rotational Cell Analyzer (LORCA). Lipid peroxidation was determined via malondialdehyde (MDA) measurements by HPLC. Melatonin alone did not change erythrocyte deformability. Oxidative stress alone decreased the deformability of erythrocytes by 25.8 +/- 3.1% (P<0.05). Melatonin pre-treatment augmented the decrease in erythrocyte deformability but prevented lipid peroxidation. Melatonin (1 microM) did not cause any additional effect on erythrocyte deformability. Higher concentrations (10-1000 microM) further decreased deformability (P<0.05). Erythrocytes exposed to oxidative stress had MDA levels of 116.3 +/- 14.3 micromol/g Hb. Melatonin (1 microM) slightly increased MDA levels, but 1000 microM melatonin reduced it by 35% (P<0.05). These findings indicate that melatonin exerts antioxidant effect on lipids. Deterioration of erythrocyte deformability may be due to a separate pro-oxidative action on proteins.

Erythrocyte deformability, plasma viscosity and oxidative status in patients with severe obstructive sleep apnea syndrome.

BACKGROUND AND PURPOSE: In patients with severe obstructive sleep apnea syndrome (OSAS), diurnal changes of plasma viscosity and erythrocyte deformability were measured to elucidate the possible mechanism of cardiovascular diseases in OSAS patients. PATIENTS AND METHODS: Plasma viscosity and erythrocyte deformability was determined in 11 OSAS patients and 11 healthy subjects matched by sex and age. Plasma viscosity was measured by a cone-plate viscometer, and erythrocyte deformability was determined by filtration technique. Whole blood counts were performed and oxidative status of the patients' plasma and erythrocytes were evaluated. RESULTS: OSAS patients had higher plasma viscosity than controls, both in the morning (1.74+/-0.3 vs. 1.36+/-0.2 mPas, P<0.002) and evening (1.55+/-0.2 vs. 1.27+/-0.1 mPas, P<0.002), and morning plasma viscosity was significantly higher than the evening level (P<0.05). Morning plasma viscosity of patients was inversely correlated with their mean nocturnal SaO(2). Morning plasma malonyldialdehyde level was significantly higher in the patients than in the controls (69.7+/-30.5 vs. 45.5+/-11.0 nmol/l, P<0.005). Erythrocyte deformability of the patients was slightly lower. CONCLUSIONS: We have observed that plasma viscosity is high both in the morning and in the evening in severe OSAS patients. This elevation may predispose OSAS patients to myocardial infarction and stroke by increasing blood viscosity. Low nocturnal mean SaO(2) may be responsible for the high plasma viscosity in these patients.

Decreased erythrocyte deformability in Behçet's disease.

Behçet's disease (BD) is a chronic recurrent systemic vasculitis of unknown cause. Thrombotic tendency is another characteristics of BD. While hemorheological changes play crucial role in thrombosis, erythrocyte deformability (ED), which is one of the main determinants of microcirculation and blood viscosity, has not been studied before in BD. ED was measured by the filtration method in 13 active BD patients diagnosed according to the criteria proposed by International Study Group for BD (ISG-BD) and in 13 age-, sex-, weight-, smoking habit-, and blood pressure-matched healthy controls. ED was decreased in active BD patients compared to the healthy control subjects. The median deformability indices (DIs) in BD patients and healthy controls were 3.19 and 2.08 (p<0.001), respectively. The decrease in ED may be one of the reasons for increased thrombotic tendency in BD. Alteration in ED possibly plays a crucial role in the etiopathogenesis of thrombotic complications in BD and thus may be a target for treatment. Drugs increasing ED, such as pentoxifylline, have already been shown to be beneficial in the treatment of BD. Therefore, we propose that the therapeutic mechanism underlying the beneficial effect of this drug in BD is likely to be the correction of impaired ED.

Hemorheology, melatonin and pinealectomy. What's the relationship? An experimental study.

The circadian rhythm of stroke and myocardial infarction (MI) may be related to the circadian rhythm of melatonin, and erythrocyte deformability may be the key mechanism in this relationship. Therefore, this study has been performed to determine if there is a relationship between the pineal gland and melatonin and red cell deformability. Twenty-eight rats underwent pinealectomy, pinealectomy plus melatonin administration (200 mg/kg), or no treatment (n=7 in each group). Erythrocyte deformability was determined using the filtration technique. The results are reported in mean (+/-SD) seconds: control: 1.45+/-0.44; pinealectomy (A): 1.55+/-0.16; pinealectomy (B): 1.34+/-0.26 and pinealectomy and melatonin: 2.56+/-0.69. Pinealectomy by itself did not cause any statistically significant change in erythrocyte deformability but the addition of melatonin significantly decreased it. These results suggest a relationship between melatonin and erythrocyte deformability. Further investigations may uncover the causes of the circadian rhythm of stroke and MI, which may help improve chronobiological therapies.