Clinical Hemorheology and Microcirculation

Stroke is the third leading cause of mortality and is one of the leading cause of disability in the world today. Although underused, anticoagulation with warfarin is still the treatment of choice for prevention of stroke in patients with AF, though hemorrhage is clearly increased in the anticoagulated patient. The substantial difficulties associated with warfarin use give reasons for the continuing challenge of decision making about antithrombotic therapy. They have led to a search for alternative approaches of stroke prophylaxis resulting in a strategy of mechanically sealing the left atrial appendage (LAA) and excluding it from the systemic circulation. A couple of years ago a percutaneous transcatheter transseptal approach to LAA occlusion has become feasible. Since then, valuable technical knowledge and a proof of concept emerged from clinical trials using three different systems. However, also the intervention bears a risk. Thus, identifying those patients who gain the most from either therapy is crucial which, in the first line, means to calculate the risk of stroke or bleeding. Unfortunately, patients with some defined comorbidities are at risk of both, cerebral embolism or hemorrhage. Whether this target group may benefit from LAA occlusion is a matter of this discussion.

The differentiation, maturation and functioning of Dendritic cells (DCs) are dynamic processes. This study investigated the changes of DCs' migration ability and biorheological properties during their differentiation. Transmigration assay showed that, DCs' migration rate was improved significantly as they differentiate (p < 0.05); NSC (Rac1 blocker) treatment could significantly decrease their migration rates (p < 0.05). Confocal images showed that, F-actin uniformly distributed in monocytes; with DC's differentiation, F-actin began to remodel and gather at the site of dendrites; the images presented surface ruffles and uneven sawtooth-like cytoskeletal structures. Fluorescence polarization analysis showed that, membrane fluidity was increased significantly with DC's differentiation (p < 0.05). CD62L was upregulated significantly (p < 0.05) on the third and ninth days. CD2 was upregulated significantly (p < 0.05) until the seventh day. DC's electrophoretic mobility was increased continuously, especially increased significantly from the third day to the fifth day and the final stage (p < 0.05). These results indicate that there are significant changes in the biorheological properties of DCs during their differentiation.

Renal masses are frequently incidentally found on ultrasound. Contrast enhanced computed tomography (CECT) is regarded as the method of choice. Contrast enhanced ultrasound (CEUS) has a high impact for characterisation of hepatic lesions. Its use in renal masses has been less comprehensively studied. Two hundred and one patients referred for surgical treatment of a renal mass, 143 patients fulfilling inclusion criteria (histology and reference method). Baseline ultrasound and CEUS with BR1, histology obtained by surgery (89%) or biopsy (11%). Eighty-eight percent of the patients had renal lesions which were malignant and 12% benign lesions. Eighty percent had renal cell carcinoma (RCC). Seven percent of the lesions were cystic. Two patients were upgraded by CEUS from CECT Bosniak II into CEUS Bosniak III resp. IV. CEUS could predict malignancy with a sensitivity, specificity, positive, negative predictive value and accuracy in 97%, 45%, 91%, 75%, and 90%. The correct staging was diagnosed by CEUS (CECT) in 83% (69%). CEUS was superior to CECT in the staging and characterisation of RCC, also in the subgroup of patients with cystic lesions. CEUS can replace CECT e.g. in patients with allergies or contraindications against CECT. Multicentre studies are necessary to confirm the findings.

Acute myocardial infarction (AMI) in young adult presents a typical pattern of risk factors, clinical, angiographic and prognostic characteristics. In the last years we demonstrated that hemorheological profile is altered in these patients in a persistent way and independently of the number of risk factors and of the extent of coronary lesions. Thus, the hyperviscosity syndrome following AMI could be considered an intrinsic characteristic of these patients. Consequently it is possible to hypothesise the presence of a genetic background at the origin of this predisposition. If this background is able to influence the risk of ischemic heart disease, this should be particularly evident in young subjects. Since inflammatory mechanisms play a central role in mediating all phases of atherosclerosis, genes encoding for inflammatory or anti-inflammatory molecules are candidates for the risk of developing atherosclerosis. As atherosclerosis is the first cause of mortality in Western countries and if pro-inflammatory genotypes contribute to risk of coronary heart disease, alleles associated to disease susceptibility should not be included in the genetic background favouring longevity: People genetically predisposed to a weak inflammatory activity have fewer chances to develop cardiovascular disease and, therefore, have better chance for a long-life. According to this hypothesis, we studied in our population of young patients with AMI, the distribution of some polymorphisms influencing a inflammation and found an higher prevalence of pro-inflammatory polymorphisms (SNP A2080G of pyrin gene, SNP Gly670Arg of PECAM gene, C1019T of Cx 37 gene, SNP G1059C of PCR gene) and a lower prevalence of anti-inflammatory polymorphisms (Asp299Gly of TLR4 gene, SNP –1082 G/A of IL10 gene, CCR5Δ32). Results of these studies show that early myocardial infarction could be associated with a genetic predisposition to an intense inflammatory response, associated also to an hyperviscosity syndrome.

The authors describe clinical cases of two patients admitted to intensive care unit following severe Plasmodium falciparum malaria. Patients' sublingual microcirculation was monitored by on-line Sidestream dark-field imaging before and after treatment with erythrocytapheresis. Before treatment, microcirculatory flow alterations were obvious. Therapy produced a rapid decrease in infected red blood cells with a significant improvement in microcirculatory flows, capillary perfusion and patients' outcome. The present cases emphasize the relevance of microcirculation monitoring in patients with capillary perfusion alterations resulting from severe malaria. As far as we know, this is the first observations of an improvement of capillary perfusion after erythrocytapheresis.

Reactive carbonyl species (RCS) have been widely used as indicators of oxidative stress. However, the associations of carbonyl stress with aging process and biochemical alteration of erythrocyte are still poorly understood. Fresh blood samples in vacutainer tubes containing sodium heparinate were obtained from 874 volunteers who were divided into young, adult and old groups based on their age. Plasma RCS and thiols concentrations between different age groups and erythrocyte membrane protein carbonylation in the adult group were detected within 24h of the blood sampling. Results showed that the plasma thiols concentration decreased gradually during aging process, and the p-values between all three groups are less than 0.05. The plasma RCS concentration in different age groups showed a nonlinear association with age. The levels in the young group were slightly higher than the adult group (not significant) and lower than the old group (p < 0.01). The protein carbonylation of erythrocyte membrane was positively correlated with plasma RCS concentration (p < 0.01), but not plasma thiols concentration. We conclude that higher levels of RCS, not lower levels of thiols, in plasma are a direct risk factor for the protein carbonylation of erythrocyte membrane. Owing to the decrease of thiols levels and increase of RCS levels during aging process, a shift from RCS-related redox allostasis to carbonyl stress would contribute to age-related biological dysfunction and even aging process.

Although there are several studies dealing with erythrocyte deformability (ED) in obese patients, research on this topic in morbidly obese subjects is scarce. In these studies ED seems to be decreased, although the cause remains unknown. A case-control study in 76 morbid obese subjects (23 women and 53 men, aged 44 ± 13 years) and in 79 normal-weight controls (30 women and 49 men, aged 43 ± 13 years) was undertaken. ED has been determined by ektacytometric techniques in a Rheodyn SSD, by means of the elongation index (EI) at 12, 30 and 60 Pascals, along with anthropometric, lipidic, metabolic and inflammatory parameters. EI was statistically lower in morbidly obese subjects than in controls at all the shear stresses tested (EI12: 47.3 ± 2.14 vs. 47.9 ± 2.07; p = 0.047, EI30: 52.16 ± 2.1 vs. 53.12 ± 1.4; p = 0.007, EI60: 53.9 ± 2.4 vs. 55.2 ± 2.50; p = 0.001) as were anthropometric lipidic and inflammatory parameters (p < 0.001). In the bivariate correlation EI60 correlated negatively with most anthropometric, lipidic and inflammatory parameters. However, in the multivariate analysis, the case-control status was not significantly associated with EI60 and only triglycerides, glucose, hs-CRP and waist circumference were independently associated with EI60, constituting independent predictors of altered ED although, waist circumference, showed the highest statistical significance (p = 0.007). ED is decreased in morbidly obese subjects associated with insulin resistance and inflammation parameters although abdominal obesity seems to be of paramount importance in altering this rheological parameter.

Many papers have showed non univocal data about oxidative stress status and nitric oxide metabolites in essential hypertension. Considering this preamble we examined the total antioxidant status (TAS), the lipid peroxidation (LP), expressed as thiobarbituric acid-reactive substances (TBARS), the stable end products of nitric oxide (NOx) and LP/NOx ratio in 25 subjects with untreated mild essential hypertension. The obtained data show a significant increase in TBARS (p < 0.001) and NOx (p < 0.001) in hypertensives and no variation in TAS and in TBARS/NOx ratio. None of these parameters was statistically related to the metabolic parameters or to the blood pressure values. The high level of lipid peroxidation observed in this group of hypertensives suggests the timely and specific employment of antihypertensive and antioxidant agents while the NOx increase seems to confirm the inflammatory status accompanying this clinical condition.