Clinical Hemorheology and Microcirculation

Tie-2 receptor has been shown to play a role in the neovascularization of tumors, but little is known about the role it may play in acute myocardial infarction (AMI). The aims of this research are (1) To study the variety of soluble Tie-2 (sTie-2) in patients with AMI. (2) To study the effects of recombinant soluble Tie-2/Fc on HUVECs viability and tube formation in vitro. Serum levels of sTie-2 in 27 patients with AMI were measured on admission (day 1), day 2, day 3 and day 7 after onset of chest pain and 28 healthy controls by ELISA. In addition, the viability of HUVECs and tube formation area were measured after stimulated with recombinant Tie-2/Fc chimera. Median level of sTie-2 increased significantly in the AMI patients when compared with the controls and the maximum level appeared at day 2 after onset of AMI. Tie-2/Fc induced EC apoptosis and inhibited HUVEC tube formation in vitro. Results of this study showed that the level of sTie-2 increased in AMI. The effects of Tie-2/Fc on EC viability and tube formation indicated that angiogenesis might be inhibited in the acute phase of AMI.

In a group of 18 subjects with acute deep venous thrombosis (DVT), evidenced by clinical examination and echo-color-Doppler, we examined the phenotypical expression of the polymorphonuclear leukocyte (PMN) beta₂-integrins (CD11a, CD11b, CD11c, CD18), obtained by using a flow cytofluorimeter. The evaluation was performed before and after in vitro activation (prolonged for 5 and 15 minutes) with 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). In DVT subjects, at baseline, the phenotypical expression of CD11b was decreased and that of CD11c was increased when compared with normal controls; no difference was found in CD11a and CD18 expression. In normal subjects PMN activation with both activators led to a constant increase of all PMN adhesion molecules; in DVT subjects CD11b, CD11c and CD18 increased, while CD11a expression did not show any change. These data indicate the presence of a functional alteration in circulating PMN cells from patients with DVT.

Ischemic preconditioning is a condition of reduced sensitivity to ischemic damage. This protective state can be induced by exposure to periods of brief, sublethal, ischemia prior to a protracted ischemic event, but, more interestingly, also by administration of specific drugs. Recent studies have emphasized the central role of free radicals (including superoxide anion and nitric oxide) in this process. In line with these observations, studies have demonstrated that also drugs such as organic nitrates, which are able to release nitric oxide (but also the highly oxidant superoxide anion) can induce preconditioning. Starting from our observations made in human experimental models regarding the effects of chronic therapy with organic nitrates, we criticize the hypothesis whereby nitrates might be used to induce a state similar to preconditioning upon chronic exposure. As well, we propose a theory for the evolutionary meaning of ischemic preconditioning based on the hypothesis that, while protective over short periods of time, continuous exposure to oxidant free radicals might be associated with a loss of this protective effect and, in certain cases, with an increased oxidative damage.

Autologus veins have been used clinically as a bypass conduit for reconstruction of small arteries, but there are few data available for microvascular response to arteriovenous (AV) shunting. This study was aimed to evaluate microvascular hemodynamic changes induced by creating AV anastomosis in rat hindlimb. Using intravital fluorescence videomicroscopy, we measured velocities of red blood cells (RBCs) flowing in the microvascular network in the control state, in the occlusion state where the superficial femoral artery (SFA) was occluded, and in the AV shunting state where the AV anastomosis was opened after occlusion of SFA. RBC velocities were measured in 155 capillaries of 6 rats using a dual window method and a frame-by-frame technique. The mean velocity and the coefficient of variation were 0.61 mm/sec and 0.90 in the control state, 0.34 mm/sec and 1.30 in the occlusion state, 0.83 mm/sec and 1.24 in the AV shunting state, respectively. These indicated that hemodynamic heterogeneity among capillaries increased with decrease in mean velocity following the arterial occlusion, while the AV shunting augmented the heterogeneity with increase in mean velocity. Capillaries with low perfusion (<0.1 mm/sec) or high perfusion (>1.0 mm/sec) were 5.8% or 20.6%, 29.6 or 5.2%, and 22.6 or 30.3% out of all measured capillaries in the control, occlusion and AV shunting conditions, respectively. In conclusion, AV shunting increased capillary perfusion and also its spatial heterogeneity, preferentially inducing high velocity in the microvasculature.

Hyperhomocysteinemia has been identified as independent risk factor for early atherosclerotic vascular disease. The purpose of our study was to investigate the plasma homocystein (Hcy) concentrations and its relationship with lipid peroxidation as thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx; nitrite plus nitrate) concentrations in age-matched non-obese (n=55) and obese (n=60) female subjects with type 2 diabetes mellitus. Non-obese diabetic patients have significantly higher plasma tHcy and TBARS (p<0.001 and p<0.001), and significantly lower NOx concentrations than the controls (n=25) (p<0.001). The plasma tHcy and TBARS concentrations were higher and nitric oxide concentrations were lower in obese diabetics than in non-obese diabetics (for each comparison; p<0.001). Correlation analysis demonstrated that there was a significant positive correlation between tHcy and TBARS (r=0.452, p<0.01) in diabetics groups. There was no significant correlation between tHcy and plasma NOx, insulin and blood pressure. We thought that Hcy might have a permissive role on the endothelium damage through free radical generating systems and the presence of obesity the free radical induced-damage has been elevated in diabetic patients.

Objective. Sudden sensorineural hearing loss is a frequent disease whose aetiology is still unknown in about 80% of patients. Aim of this study was to evaluate if haemorheological changes and some indexes of hypercoagulability and hypofibrinolysis are associated with idiopathic sudden sensorineural hearing loss (ISSHL). Methods. We studied 63 patients with ISSHL and 67 healthy control subjects, matched for age, sex and traditional cardiovascular risk factors. Haemorheological studies were performed by assessing whole blood viscosity (WBV) at 0.512 s⁻¹ and 94.5 s⁻¹, plasma viscosity (PLV) and erythrocyte deformability index (DI). To assess whole blood coagulation Sonoclot analysis was performed. Sonoclot variables studied were Sonoclot activated clotting time (SonACT), clot rate and time to peak. Fibrinogen, PAI-1 antigen (ag) and factor VIII:C plasma levels were also measured. Results. WBV, PLV, SonACT, clot rate, time to peak, PAI-1ag and factor VIII:C were significantly altered in patients in comparison with controls (p<0.05). A multivariate analysis (adjusted for traditional cardiovascular risk factors, hematocrit, fibrinogen, haemostatic and haemorheological variables) indicated that WBV at 94.5 s⁻¹, DI, SonACT, clot rate, PAI-1ag plasma levels and factor VIII:C activity were independently associated with ISSHL (p<0.05). Conclusions. The observed changes in viscosity, blood clotting and fibrinolysis may contribute, at least in part, to the pathophysiological mechanism of ISSHL.

Purpose: To assess the vascularization and the perfusion within hepatocellular carcinoma (HCC) including treatment-related changes with contrast-enhanced (CE) ultrasound (US). Materials and methods: Twenty-six biopsy-verified HCC lesions (size between 2.5–8 cm, median 3.8 cm) in 20 patients were examined with unenhanced and CE vascular US techniques immediately before selective angiography for transarterial chemoembolization (TACE) as well as immediately after TACE using all of the following modalities: color-coded Doppler sonography (CCDS), power Doppler imaging (PDI), CE pulse inversion harmonic imaging with PDI (PIHI+PDI), and CE coded harmonic angiography (CHA). In CE US studies, perflutren protein-type A microspheres were administered as contrast agent in a single 0.5 ml i.v. bolus diluted in 20 ml 0.9% NaCl. Selective arteriograms and CE computed tomographies were taken for reference purposes. The Wilcoxon test was used for statistical analysis. Results: Intratumoral vessels could be visualized before TACE in 11/26 lesions (42%) with CCDS; in 15/26 (58%) with PDI; in 23/26 (88%) with CE CHA; in 26/26 (100%) with CE PIHI+PDI. Following TACE, the sensitivities were calculated as follows: CCDS 33%; PDI 55%; CE CHA 77%; and CE PIHI+PDI 100%. The corresponding negative predictive values were 74% for CCDS; 81% for PDI; 89% for CE CHA and 100% for CE PIHI+PDI. During the capillary phase, contrast enhancement could be observed in the CHA mode only. Conclusion: CE US by means of PIHI+PDI and CHA enables reliable visualization of residual tumor following TACE equivalent to that which is attained with angiography and Contrast Harmonic Imaging with Power Doppler, if perflutren microspheres are used as contrast agent in a single low-dose bolus.

In patients with iron deficiency anaemia (IDA) it has been suggested that the shortened erythrocyte lifespan may be in part due to decreased erythrocyte deformability. In order to know whether erythrocyte deformability is decreased in IDA patients, we have determined the erythrocyte Elongation Index (EI) by means of ektacytometric techniques (Rheodyn SSD, Myrenne Gmbh, Germany), in 50 IDA patients and 100 well age and sex matched healthy controls. At the three shear stresses tested, 12, 30 and 60 Pa, IDA patients show statistically lower EI than controls (37.4±6.7 vs 48.6±2.9; 45.0±6.0 vs 54.5±2.8; 48.7±5.8 vs 57.0±2.9 mPa·s, respectively; p<0.001). A statistically significant correlation was found between EI at 12, 30, and 60 Pa and the hematimetric indices (MCV, MCH and MCHC), suggesting that the alteration in surface/volume ratio (shape) which characterizes this kind of microcytic hypocromic anaemia, accounts in part for the decreased EI. Rheodyn SSD, as an ektacytometric technique, is very sensitive to alterations in red blood cell geometry, for what seems to be a useful tool for detecting diminished erythrocyte deformability in IDA patients.

In patients with iron deficiency anaemia (IDA) it has been suggested that the shortened erythrocyte lifespan may be in part due to decreased erythrocyte deformability. In order to know whether erythrocyte deformability is decreased in IDA patients, we have determined the erythrocyte Elongation Index (EI) by means of ektacytometric techniques (Rheodyn SSD, Myrenne Gmbh, Germany), in 50 IDA patients and 100 well age and sex matched healthy controls. At the three shear stresses tested, 12, 30 and 60 Pa, IDA patients show statistically lower EI than controls (37.4±6.7 vs 48.6±2.9; 45.0±6.0 vs 54.5±2.8; 48.7±5.8 vs 57.0±2.9 mPa·s, respectively; p<0.001). A statistically significant correlation was found between EI at 12, 30, and 60 Pa and the hematimetric indices (MCV, MCH and MCHC), suggesting that the alteration in surface/volume ratio (shape) which characterizes this kind of microcytic hypocromic anaemia, accounts in part for the decreased EI. Rheodyn SSD, as an ektacytometric technique, is very sensitive to alterations in red blood cell geometry, for what seems to be a useful tool for detecting diminished erythrocyte deformability in IDA patients.