Clinical Hemorheology and Microcirculation

This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH).

Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups.

MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced.

Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.

The human scavenger receptor class B type 1 (hSR-B1), which serves as a high affinity receptor for HDL, is expressed on platelet surface and mediates various anti-atherogenic functions. Based on the anti-thrombotic effect of HDL and the importance of HDL–SR-B1 in the formation of atherosclerotic plaque, the present study was aimed to investigate and compare the expression level of hSR-B1on platelets of CAD patients with that of normal controls.

The expression of the hSR-B1 on platelets of 31 CAD patients with atherosclerotic plaque and 20 healthy controls were detected using flowcytometry and western blotting. Moreover, platelet function in response to the agonists was examined by aggregometry, and the lipid panel tests were assayed using chemistry autoanalyzer.

Our findings showed that the expression of hSR-B1 was significantly reduced on the surface of platelets from CAD patients with atherosclerotic disease, as compared with healthy controls (6/8% vs. 13/6%) (P < 0,001). Of particular of interest, we also found that the formation of aggregates after stimulation of the platelets with ADP was higher in patients with atherosclerotic disease than the controls; indicating an inverse relationship between hSR-B1 expression and the function of human platelets.

Taken together, the results of the present study raise the possibility that the measurement of hSR-B1 expression on human platelets may provide a valuable insight that reflects the status of RCT in patients with atherosclerosis.

To compare the enhancement pattern of hepatic angiomyolipoma (HAML) on contrast enhanced ultrasound (CEUS) and magnetic resonance (MR).

The data of seven patients (females; age 28–52 years; mean, 42 years) with histologically proven HAMLs were retrospectively reviewed. All patients underwent CEUS and MR examination. The images were analyzed by two experienced doctors who blinded to the clinical and pathological information of cases.

The mean diameter of the nodule was 5.7 cm (range: 3.2–10 cm). Histopathologic results revealed 4 nodules to be myomatous type and 3 nodules to be mixed type. All nodules showed hyperenhanced during arterial phase on both CEUS and MRI. During portal and delayed phase, washout was more showed on MRI (5/7, 71.4%) than on CEUS (2/7, 28.6%).

There is discrepancy of enhancement pattern between CEUS and MRI. The quick wash-in and sustained hyperenhancement on CEUS may be helpful for the diagnosis of HAML.

Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants commonly used in cardiovascular diseases (CVDs), inhibit the re-uptake of serotonin not only into neurons but also into platelets. Hence they increase the level of serotonin in plasma.

This study was aimed to clarify the effects of two selected SSRIs on plasma serotonin level, hemorheological parameters (hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity) and selected oxidative stress markers (MDA, GSH, GSSG levels in plasma and erythrocytes).

Two different SSRIs (Fluvoxamine and Sertraline) were administered to male Sprague-Dawley rats in acute (5 days) or chronic fashion (21 days) at 20 mg/kg/day dose.

Aggregation amplitude (AMP) decreased significantly in the chronic sertraline and acute fluvoxamine groups; aggregation half time (t1/2) decreased significantly in the chronic fluvoxamine group. Biochemical parameters indicating oxidative stress significantly increased in the chronic sertraline group.

Since SSRI’s are commonly used in patients with CVDs, complementary studies are needed to assess the impact of such changes in hemorheological parameters on the risk for CVD, and to reveal the effects of other SSRIs on hemorheological parameters.

Enhancement patterns on contrast-enhanced ultrasound (CEUS) help to distinguish different liver tumors.

Assessing the diagnostic value of dynamic contrast-enhanced ultrasound (DCEUS) for the discrimination of different malignant liver lesions.

148 malignant focal liver lesions were assessed prospectively with DCEUS (hepatocellular carcinoma = HCC; cholangiocellular carcinoma = CCC; pancreatic adenocarcinoma = PCA; breast cancer = BC; colorectal cancer = CRC; melanoma = MM). Focal-nodular-hyperplasias (FNH) served as a reference for benign lesions. DCEUS-clips were recorded continuously over three minutes. DCEUS-values were compared between the tumor entities. For better inter-individual comparability, perfusion kinetics were analyzed considering the perfusion characteristics of the surrounding liver parenchyma (Relative Signal Intensity = RSI: lesion-liver tissue/liver tissue) at different points in time.

Absolute signal intensity in FNH showed a tendency towards higher values compared with malignant liver lesions [Peak Enhancement(a.u.): FNH 7111.4; HCC 549.9; CCC −6654.3; PCA −7307.9; BC −4562.4; CRC −10672.9; MM −3034.1]. Washout was significantly less in FNH versus PCA and CRC, and more pronounced and earlier in PCA and CRC versus HCC [RSI 30 seconds after PE-lesion(%): FNH +52; PCA −65; CRC −76; HCC −26]. Rise Time, Fall Time and mean-Transit-Time did not differ significantly.

DCEUS-values reflect significant differences between malignant liver lesions, especially at peak enhancement and during the washout phases.

A native AV-fistula (AVF) for access in hemodialysis (HD) is preferable. Stenosis, a major hurdle, is associated with older age and diabetes mellitus.

This case-control study aimed to clarify if any medical and/or laboratory factors, that can be altered, could be associated to AVF stenosis.

33 patients with a patent AVF without need of intervention during a two year period (Controls) were matched by diagnosis and age with 33 patients (Cases), that had at least one radiological invasive examination/intervention due to suspected AVF malfunction (case-control mode 2:1).

Cases had higher weekly doses of Erythropoietin-Stimulating Agent (ESA) than Controls both before intervention (mean 8312±7119 U/w versus 4348±3790, p = 0.005) and after the intervention (7656±6795, versus 4477±3895, p = 0.018). Before intervention serum phosphate was higher in Cases while there was no significant difference in blood hemoglobin, weekly standard Kt/V, parathyroid hormone, calcium, albumin, C-reactive protein, smoking habits, BMI or other medication.

Higher doses of ESA were administered in patients with AVF stenosis. Since ESA may cause local hypertrophic effects on the vascular endothelium, we should prescribe lower doses of ESA in patients at risk. Further studies should clarify such connection.

Patients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx.

This trial evaluates the effect of hydrocortisone on glycocalyx integrity in patients undergoing cardiac surgery with cardiopulmonary bypass.

In a prospective, randomized interventional pilot trial, 30 patients received either hydrocortisone (100 mg over 10 min) or placebo (saline control) before surgery. Plasma concentrations of glycocalyx constituents (syndecan-1, heparan sulfate) and various clinical parameters (respiratory and renal function, inflammatory markers, use of vasopressors, length of stay at the intensive care unit) were measured. Primary endpoint was a significant difference of glycocalyx constituents in plasma. Comparisons were made with Friedman’s and Wilcoxon tests (paired data), or the Kruskal-Wallis and Mann-Whitney U tests (unpaired data). Holm-Bonferroni method was used for post-hoc corrections.

Heparan sulfate and syndecan-1 increased significantly during and after cardiac surgery with cardiopulmonary bypass in both groups. Whereas the maximum increase of heparan sulfate was 12.3-fold in the control vs. 3.8-fold in the pretreated group (p < 0.05), syndecan-1 values showed no significant difference between the groups (maximal increase 3-fold). The inflammatory markers C-reactive protein and interleukin-6 were also higher in the control than in the hydrocortisone group, but there was no difference in patient mortality (zero), or in any clinical parameters.

Pretreatment with hydrocortisone ameliorated shedding of heparan sulfate, a major constituent of the endothelial glycocalyx, in patients undergoing cardiac surgery with cardiopulmonary bypass, but had no relevant influence on various clinical parameters or patient mortality. The relatively small number of patients in this pilot study probably precluded detection of positive outcome differences.

Preclinical studies report that higher plasma viscosity improves microcirculatory flow after haemorrhagic shock and resuscitation, but no clinical study has tested this hypothesis.

We investigated the relationship between plasma viscosity and sublingual microcirculatory flow in patients during resuscitation for traumatic haemorrhagic shock (THS).

Sublingual video-microscopy was performed for 20 trauma patients with THS as soon as feasible in hospital, and then at 24 h and 48 h. Values were obtained for total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index (MFI), microcirculatory heterogeneity index (MHI), and Point of Care Microcirculation (POEM) scores. Plasma viscosity was measured using a Wells-Brookfield cone and plate micro-viscometer. Logistic regression analyses examined relationships between microcirculatory parameters and plasma viscosity, adjusting for covariates (systolic blood pressure, heart rate, haematocrit, rate and volume of fluids, and rate of noradrenaline).

Higher plasma viscosity was not associated with improved microcirculatory parameters. Instead, there were weakly significant associations between higher plasma viscosity and lower (poorer) MFI (p = 0.040), higher (worse) MHI (p = 0.033), and lower (worse) POEM scores (p = 0.039).

The current study did not confirm the hypothesis that higher plasma viscosity improves microcirculatory flow dynamics in patients with THS. Further clinical investigations are warranted to determine whether viscosity is a physical parameter of importance during resuscitation of these patients.

To evaluate the efficacy of added shear wave elastography (SWE) in breast screening for women with results inconsistent between mammography and conventional ultrasounds (US).

The study consisted of 282 pathologically proven breast lesions. The cancer probability from screening by mammography and conventional US were scored using Breast Imaging Reporting and Data System (BI-RADS). Elastography was used to re-evaluate inconsistent conventional US and mammography results. The diagnostic performance of conventional US, mammography, and Combined conventional clinical imaging and SWE was compared. The clinicopathological features of all breast cancer patients with inconsistent (and consistent) conventional US and mammography findings were compared.

Finally, 147 lesions were confirmed benign and 135 were malignant. The AUC of Combined conventional clinical imaging plus elastography imaging (0.870) was significantly higher than mammography (0.735, p < 0.001) or conventional US (0.717, p < 0.001) alone. Among the 135 breast cancers, 79 of the conventional US and mammography findings were consistent and 56 were inconsistent. Younger age(<50y) (p = 0.035), non-invasive (p = 0.037), smaller size (p = 0.002) and negative lymph node status (p = 0.026) were significantly associated with inconsistent findings.

The added SWE in breast screening when inconsistent results from mammography and conventional US occurred is necessary and effective.

The aim of this study was to investigate the relationship between red blood cell (RBC) aggregation and deformability and angiogenesis parameters in obese patients.

We studied 35 obese subjects and 20 non-obese people as a control group. Angiogenesis was detected using Bio-Plex Pro Human Angiogenesis Multiplex Assays. The RBC aggregation and deformability of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser – LORCA.

The aggregation index and the syllectogram’s amplitude were significantly higher in the obese patients, whereas the aggregation half-time (t_1/2) was lower compared with the control group. The deformability of RBC expressed as EI was significantly lower in the obese group than it was in the control group. All angiogenesis parameters were higher in obese individuals than they were in the control group. Significant differences were observed in angiopoietin 2 (p = 0.048), folistin (p = 0.0017), G-CSF (p = 0.042), HGF (p = 0.016), and PECAM-1 (p = 0.014). The VEGF tended to be higher in the obese patients than in the control group (p = 0.09); nevertheless, the concentration of PDGF-BB was similar in both groups. EI at shear stresses of 18.49 Pa and 30.2 Pa was strongly correlated with all angiogenesis parameters. No correlations were found between the studied RBC aggregation indices and angiogenesis parameters. Multivariate analyses indicated that only HGF was an independent predictor of RBC deformability at 18.49 Pa (β–0.83, P < 0.000005) and at 30.2 Pa (β–0.83, P < 0.00005).

The study found that there are relationships between enhanced RBC rigidity and angiogenesis status in obese subjects. Because this correlation between angiogenesis and RBC deformability is presented for the first time, the physiological importance of the relationship requires further research.

The viscosity of a fluid is a measure of its resistance. It is the thickness and stickiness of blood, and a direct measure of the resistance of blood to flow through the vessels. Various factors in the blood have direct or indirect impact on blood viscosity. These hemorheological factors play an important role in the pathogenesis of many diseases. Glucose is one such factor, which, when increased in the blood, causes resistance in the blood flow.

The present study is aimed to assess the changes in blood viscosity associated with hyperglycemia in rodents.

Diabetic patients were grouped, depending on the duration of their diabetic status assessed by their increased HbA1c. Similarly rodents were subjected to acute or chronic hyperglycemic conditions in various experiments. In vivo, perfusion study was performed using micro probe in diabetic mice. Flow cytometry was used to assess the expression of VCAM-1 on endothelial surface.

An approximate 40% increase in blood viscosity is observed in individual who were diabetic for the past 15 years than those who were diagnosed just one year back. Similarly such increase in blood viscosity was evident in different experiments of rodents. Our in vivo perfusion study did not showed conclusive finding however long term hyperglycemia can have deleterious effect on flow rate. Vascular pathology which was evident from the data of flow cytometry, where increase in VCAM-1 expression on the endothelial surface was observed in response to glucose and in diabetic mice.

Hyperglycemia implicates the blood viscosity which in turn can have tedious effect on metabolic syndromes thus causing the serious effect in the tissue perfusion of an organs.

Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.

We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.

We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test.