Clinical Hemorheology and Microcirculation

HIV-infected patients are at increased cardiovascular risk. Although several studies have analyzed the hemorheological profile in these patients, studies dealing with erythrocyte deformability are scarce. Moreover, studies have been performed in HIV patients on antiretroviral treatment which may influence this rheological parameter. We analyzed erythrocyte deformability (Elongation Index) at 12, 30 and 60 Pa by means of the Rheodyn SSD in 34 naïve HIV-infected patients (22 males and 12 females) and 34 HIV negative control subjects (24 males and 10 females). Erythrocyte indices (MCV, MCH, MCHC), reticulocytes, plasma lipids, iron, folic acid, vitamin B12 and hepatic enzymes were also determined. When compared with controls, naïve HIV-infected patients showed lower total cholesterol, iron, bilirubin and folic acid (p = 0.009, p = 0.003, p = 0.004, p = 0.004, respectively) and higher triglycerides (TG), aspartate aminotransferase (AST) and gamma glutamyl transferase (γGt) levels (p = 0.017, p = 0.042, p = 0.004, respectively). In the multivariate regression analysis, MCV, γGt and triglycerides were independent predictors of EI60. Neither erythrocyte indices nor reticulocyte count showed differences (p > 0.05). No differences in the Elongation Index at any of the shear stresses tested (12, 30, 60 Pa) were found (p > 0.05). The results of the present study indicate that naïve HIV-infected patients not on antiretroviral treatment do not present decreased erythrocyte deformability when compared with HIV negative control subjects.

Objectives: Red blood cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, has recently been shown to be a strong predictor of adverse outcomes in patients with a great spectrum of cardiovascular disease. Recently, cholesterol content of erythrocytes membranes (CEM) has been associated with clinical instability in coronary artery disease whilst it has been linked with red blood cells (RBC) size and shape. Since the biological mechanisms underlying the association of higher RDW with cardiovascular mortality risk are currently unclear, we studied the association of CEM with RDW. Methods: 296 consecutive angina patients (236 men, mean age 69 ± 2 years) were prospectively assessed; 160 had chronic stable angina (CSA) and 136 had an acute coronary syndrome (ACS). Results: Patients presenting with ACS had increased CEM levels (121.6 μg/mg (40.1) vs 74.4 μg/mg (26.6), p < 0.001) as well as exhibited greater anisocytosis (13.9% (0.9) vs 13.3% (0.7), p < 0.001) compared to patients with CSA. Simple correlation analysis showed that CEM levels were positively associated with RDW values (r = 0.320, p < 0.001). Multivariable linear regression showed that CEM levels were associated with RDW values independently from possible confounders (inflammatory, nutritional renal or hematological). Conclusions: Data from the present study showed an independent association between cholesterol content of erythrocyte membranes and anisocytosis. Increased CEM levels -a novel biomarker of clinical instability in CAD - may facilitate our understanding why RDW is associated with increased morbidity and mortality in cardiovascular disease.

Although microcirculatory disturbances play pivotal role in the pathomechanism of acute pancreatitis (AP), very few papers can be found which had been tested any of hemorheological parameters. The aim of our study was to analyze the hemorheological changes in cerulein-induced experimental acute pancreatitis in rat in two doses (5 and 10 μg/kg, s.c.). Male and female rats were subjected to Control group, or AP with 5 or 10 μg/kg cerulein groups. Blood samplings (lateral caudal vein) were completed before cerulein administration, and 1, 2 and 24 hours later. Hematological parameters, amylase activity, erythrocyte deformability (ektacytometry) and aggregation (light-transmission method) were tested. The presence of AP could be confirmed by amylase testing and histological examination. The earliest impairment of the red blood cell deformability could be observed 1 hour after cerulein administration in 10 μg/kg dosage. Female animals had the worst rheological results with high mortality. In conclusion, subcutaneously administrated cerulein in dosage of 5 and 10 μg/kg resulted in AP in rats, with significant changes in red blood cell deformability and alterations in erythrocyte aggregation. This model seems to be suitable for further comparative studies.

Background: Hemodialysis patients have increased mortality from cardiovascular complications. Whole blood viscosity (WBV) and red cell aggregation (RCA) may influence the pathogenesis of vascular complications in this population. The objective of this study was to determine whether the hemodialysis treatment or vascular complications were associated with impaired WBV or RCA. Methods: This prospective, cross sectional investigation included 38 patients receiving chronic hemodialysis. Blood samples for WBV, RCA and hematocrit were drawn before and after dialysis. WBV was determined between 10 and 780 s⁻¹ and RCA was measured by calculating aggregate shape parameter. WBV and RCA were subsequently assessed for correlation with a history of vascular disease. Results: The mean WBV, aggregate shape parameter, and hematocrit post-dialysis were significantly higher than pre-dialysis values (p < 0.05). Using a linear model with WBV as the dependent variable, the covariates of aggregate shape parameter, hematocrit, weight, and history of diabetes were not significant. However, pre/post timing of the sample was a significant covariate. WBV correlated with prior access thrombosis or stenosis, especially if the patient had a history of peripheral vascular disease. Conclusions: Higher WBV correlated with an increased incidence of access failure and vascular disease. Repetitive increases in WBV and RCA with each dialysis treatment could contribute to vascular dysfunction in this patient population.

Primary open-angle glaucoma (POAG) is one of the most common types of glaucoma. Glaucoma is a progressive neuropathy of the optic nerve with characteristic visual area disorders. The aim of this study was to assess the correlations between rheological parameters of blood and other parameters such as: intraocular pressure, visual acuity, angular breadth of the aqueous fluid eluvium, visual area and arterial hypertension. The examined group was comprised of 54 patients with POAG. Out of this group two subgroups was separated: I subgroup of 24 patients without hypertensive and II subgroup of 30 patients with chronic hypertensive disease. The control group was comprised of 40 healthy subjects. Erythrocyte aggregation and deformability analysis were determined using LORCA. From the results we concluded that rheological disorders such as enhanced erythrocyte aggregation or significantly decreased erythrocyte deformability occur in patients with POAG. Additionally, it revealed a significant relation between the duration of hypertension and an increased erythrocyte aggregation index (r = +0.27 p < 0.005) along with decreased deformability (r = −0.37 p < 0.001), where the decrease in deformability correlated with the severity of hypertonic retinal angiopathy (r = −0.30 p < 0.05). All these disorders may result in decreased blood flow to the optic nerve, which contributes towards the development of neuropathy.

This in vitro study investigated time-related effects of propofol at the plasma concentrations required for sedation and general anaesthesia, on RBC aggregation, deformability, and morphology. Blood containing propofol at plasma concentrations of 0, 2 and 4 μg ml⁻¹ was incubated in a water bath at 37°C for 1, 2, or 4 hours. RBC elongation indices (EIs) and aggregation indices (AIs), which represent RBC deformability and aggregation, respectively, were measured. Also, RBC morphological indices (MIs), which represent RBC morphology, were calculated. EIs and AIs were similar at propofol concentrations of 0, 2, or 4 μg ml⁻¹ after 1, 2, or 4 hours of incubation. MIs at propofol plasma concentrations 0 or 2 μg ml⁻¹ were similar after 1, 2, and 4 hours of incubation, however, MI at a propofol concentration of 4 μg ml⁻¹ after 4 hours of incubation was higher than its value after 1 or 2 hours of incubation. No significant difference was observed between MIs at propofol plasma concentrations 0, 2, or 4 μg ml⁻¹ after 1, 2, and 4 hours of incubation. At clinical doses, propofol has no direct effects on RBC deformability, aggregation, or morphology over a 4 hours incubation period.

Background: Activated polymorphonuclear neutrophils (PMN) play an important role in the microcirculation. Nitric oxide (NO) reduces the sequestration of PMN in the narrow vessels of various organs and, therefore, may reduce organ injury during inflammation. Objectives: Since PMN of term neonates show various functional differences compared to PMN in adults (decreased chemotaxis, decreased intracellular killing, decreased adhesion), we studied the influence of the semi-synthetical NO-donor FK-409 (4-Ethyl-2-hydroxyimino-5-nitro-3-hexenamide) on the deformability of IL-8 activated PMN in term neonates and adults. Methods: A cell transit analyzer (CTA) was used to study transit times of individual PMN through 8 μm filter pores, neutrophil elastase concentrations were determined by enzyme-immunoessay and activation of PMN was classified by mircroscopic evaluation. Results: The transit times of PMN activated by IL-8 in adults were 9.3 ± 2.9 s, in term neonates 10.7 ± 3.3 s. FK-409 improved the transit time of activated PMN in adults (5.4 ± 1.6 s) and in term neonates (5.6 ± 1.1 s). Despite of the functional differences of PMN in term neonates and adults, the improvement of the transit times by FK-409 was not different between the two groups. The NO donor decreased the neutrophil elastase concentrations and the morphological signs of activation in neonates and adults. Conclusions: We conclude that the NO-donor FK-409 improves the microcirculation by increasing the deformability of IL-8 activated PMN. NO may reduce in neonates tissue damage by reduced PMN sequestration due to decreased PMN rigidity.