Clinical Hemorheology and Microcirculation - Volume 48, issue 4

Authors: Chen, Chao-Hsiang | Chien, Mei-Yin | Liang, Yu-Chih | Liu, Der-Zen | Hu, Miao-Lin

Article Type: Research Article

Abstract: Free radicals play a critical role in causing hemorheologic abnormality which is highly correlated with cardiovascular disease and stroke. In this study, we established an in vitro model to evaluate the influence of free radical attacks on hemorheological parameters. A well-sealed chamber with hyperbaric oxygen was used to simulate an environment of free radical attacks. Hemorheological parameters, including whole blood viscosity, erythrocyte membrane lipid peroxidation, and erythrocyte deformability, were investigated. We then used the in vitro model to evaluate the anti-free radical effects of some well-known catechin antioxidants, such as epigallocatechin gallate (EGCG), (-)-epicatechin 3-gallate (ECG), and (-)-epigallocatechin (EGC) on …abnormal hemorheological parameters induced by hyperbaric oxygen. The results show that an increase in oxygen partial pressure (1.0, 1.5, 2.0 and 2.5 atm) and exposure time (4, 8, 12 and 16 h) resulted in elevated free radical formation and viscosity of whole blood, enhanced lipid peroxidation in erythrocyte membranes, but decreased erythrocyte deformability. In addition, EGCG, ECG, and EGC (0.1, 0.5 and 1.0 μM) effectively ameliorated hemorheologic abnormality and enhanced erythrocyte deformability. Therefore, this study has provided an in vitro hyperbaric oxygen model to rapidly screen or assess the efficacy of functional foods and drugs in the prevention or improvement of hemorheologic abnormality. Show more

Keywords: Blood viscosity, catechin, erythrocyte deformability, hyperbaric oxygen

DOI: 10.3233/CH-2011-1412

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 211-221, 2011

Authors: Son, Kuk Hui | Ahn, Chi Bum | Lee, Sung Ho | Noh, Insup | Shin, Eunkyoung | So, Mijin | Kim, Hyuna | Sun, Kyung | Kim, Kwang Taik

Article Type: Research Article

Abstract: Purpose: The advantages of blood cardioplegia, which is used for myocardial protection during open heart surgeries, include superior oxygen-carrying capacities, better osmotic properties, and the presence of more antioxidants than a crystalloid counterpart. Although, hyperkalemic organ-preserving solutions for transplantation surgeries are known to decrease RBC deformability essential for tissue perfusion, only few studies have addressed the changes in RBC deformability after exposure to cardioplegic additives. The purpose of this study was to measure deformability and oxygen-delivery capacities in various blood cardioplegic solutions. Methods: Blood from eight healthy volunteers was used. Each sample (100 ml) was divided into 5 groups of …16 ml, and cardioplegia solutions were added (group NS; blood + normal saline, group K; blood + KCl, group D; blood + KCl + diltiazem, group A: blood + KCl + adenosine, group E: blood + KCl + neutrophil elastase inhibitor [Sivelestat]). All samples were incubated at a temperature of 8°C for 10 minutes. Deformability, NO level, 2,3-DPG, and ATP were measured. Results: There was no statistically significant difference (p = 0.92) in deformability between the groups. The NO levels were not significantly different (p = 0.86). The 2,3-DPG (p = 0.27) and ATP levels (p = 0.40) were not significantly different. Conclusions: The deformability and oxygen carrying functions of RBCs did not show a significant difference according to various components of cold blood cardioplegia during 10 minutes of incubation. Show more

Keywords: Erythrocyte deformability, extracorporeal circulation, 2,3-dipalmitoylglyceric acid, microcirculation

DOI: 10.3233/CH-2011-1413

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 223-229, 2011

Authors: Muravyov, A.V. | Tikhomirova, I.A. | Maimistova, A.A. | Bulaeva, S.V. | Mikhailov, P.V. | Kislov, N.V.

Article Type: Research Article

Abstract: This study was designed to investigate whether the red cell aggregation depends on its initial level under drug therapy or cell incubation with bioactive chemical compounds. Sixty six subjects were enrolled onto this study, and sub-divided into two groups: the first group of patients (n = 36) with cerebral atherosclerosis received pentoxifylline therapy (400 mg, thrice daily) for 4 weeks. The patients of the second group were initially treated with Epoetin beta 10,000 units subcutaneously thrice a week, for 4 weeks. The second group – adult anemic patients (n = 30) with the confirmed diagnosis of solid cancer (Hb < …100 g/L). After 4 weeks of pentoxifylline treatment the red cell aggregation increased (p < 0.05) in the patients with initially low RBCA. On the other hand in the patients with initially high RBCA treatment with pentoxifylline reduced it markedly (p < 0.01). In vitro experiments with pentoxifylline RBC incubation resulted in a decrease of the initially high RBCA by 47% (p < 0.01), whereas in the sub-group with initially low RBCA it increased. It was observed that after 4 weeks of epoetin-beta treatment 75% the anemic patients with initially high RBCA had an aggregation lowering. The drop of aggregation was about 34% (p < 0.01). At the same time 25% of the study patients had a significant RBCA increase (p < 0.05) after treatment. The initially low red cell aggregation after incubation with epoetin-beta was markedly increased by 122% (p < 0.05). On the contrary initially high RBCA was reduced by 47% (p < 0.05). When forskolin (10 μM) was added to the RBC suspensions the RBCA was increased in sub-group of subjects with initially low aggregation and it was decreased in sub-group with initially high one. The similar RBCA changes were observed when RBC suspensions were incubated with vinpocetine, calcium ionophore (A23187), Phorbol 12-myristate 13-acetate (PMA) as a protein kinase C (PKC) stimulator. A major finding of this study is that the red cell aggregation effects of some drugs depend markedly on the initial, pre-treatment aggregation status of the patients. These results demonstrate that the different red blood cell aggregation responses to the biological stimuli depend strongly on the initial, pre-treatment status of the subject and the most probably it is connected with the crosstalk between the adenylyl cyclase signaling pathway and Ca2+ regulatory mechanism. Show more

Keywords: Red blood cell aggregation, cerebral atherosclerosis, anemia, pentoxifylline treatment, vinpocetine, epoetin beta, forskolin, Ca\(^{\rm{2+}}\) ionophore

DOI: 10.3233/CH-2011-1415

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 231-240, 2011

Authors: Vayá, Amparo | Suescun, Marta | Hernández, Jose Luis | Pérez, María Luz | Palanca, Sarai | Laiz, Begoña

Article Type: Research Article

Abstract: Although several studies have been published regarding rheological behaviour of red blood cells in beta and delta-beta thalassaemia traits, little information about erythrocyte deformability in alpha-thalassaemia carriers is available. We aimed to determine erythrocyte deformability in heterozygous (silent, -α/αα) and homozygous (minor alpha-thalassaemia, -α/-α) carriers of the alpha-thalassaemia trait for the alpha 3.7 deletion, the most common in our geographical area. We evaluated erythrocyte deformability by means of the elongation index (EI) in a Rheodyn SSD at 12, 30 and 60 Pa, along with basic haematological cell count, erythrocyte indices, reticulocytes, plasma lipids and iron metabolism parameters in 36 (18 …women, 18 men) alpha-thalassaemia carriers (17 heterozygous, 19 homozygous) and 36 healthy subjects (23 women, 13 men). The molecular diagnosis of the alpha 3.7 deletion was evaluated by a PCR-based method. Alpha-thalassaemia carriers presented higher red blood cell counts, RDW-CV (p < 0.001) and lower haemoglobin, MCV, MCH and MCHC (p < 0.001) than controls. EI was statistically lower at 12, 30 and 60 Pa in cases than in controls (p = 0.001, p = 0.002, p = 0.010, respectively). No differences in either elongation indices or haematimetric values were observed when comparing silent heterozygous and minor homozygous alpha-thalassaemia carriers (p > 0.05). Pearson's bivariate correlation showed that EI60 correlated positively with haemoglobin and MCV, MCH, MCHC (p < 0.01), but negatively with ferritin (p< 0.05) and RDW-CV (p< 0.01). In the multivariate regression analysis, MCV (p = 0.001) and haemoglobin (p < 0.001) predicted EI60, with this model accounting for around 43% of variation in EI60 (R2 = 0.427). Alpha-thalassaemia carriers phenotypically showed mild microcytosis and hypochromia, irrespectively of them being silent heterozygous or minor homozygous alpha-thalassaemia carriers, which is associated with decreased erythrocyte deformability. Show more

Keywords: Erythrocyte deformability, alpha-thalassaemia, silent heterozygous alpha-thalassaemia (-α/αα), minor homozygous alpha-thalassaemia (-α/-α)

DOI: 10.3233/CH-2011-1416

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 241-246, 2011

Authors: Vayá, Amparo | Hernández-Mijares, Antonio | Suescun, Marta | Solá, Eva | Cámara, Rosa | Romagnoli, Marco | Bautista, Daniel | Laiz, Begoña

Article Type: Research Article

Abstract: There are few studies on haemorheological disturbances in morbidly obese patients. The role played by the metabolic syndrome on the rheological profile of morbidly obese subjects has not yet been established, and it is not clear whether morbidly obese, but “metabolically healthy”, show rheological alterations. We aimed to determine the whole rheological profile in 136 morbidly obese patients and 136 normo-weight volunteers, along with plasma lipids, inflammatory and insulin resistance parameters. Patients had statistically higher glucose, triglycerides, HbA1c, leptin, insulin, HOMA, CRP, leucocytes, fibrinogen, plasma viscosity (p < 0.001, respectively), erythrocyte aggregation at 3 s−1 (p = 0.011) and …lower erythrocyte elongation index 60 Pa (p = 0.015). In the multivariate regression analysis, the anthropometric, lipidic, insulin resistance and inflammatory parameters predicted haemorheological variables (p < 0.001). No differences were observed for the rheological parameters when morbidly obese subjects with (n = 75) and without (n = 61) the metabolic syndrome were compared (p > 0.05), indicating that the altered rheological profile not only related to the metabolic syndrome, but to obesity itself. When further patients were classified as “metabolically healthy” obese (n = 23) and “metabolically unhealthy” obese (n = 113), the latter presented higher insulin resistance (insulin p < 0.01, HOMA p < 0.05, glucose p < 0.001, triglycerides p < 0.05 and HbA1c p < 0.01) than the former, but no differences in the rheological parameters (p > 0.05) were observed. When “metabolically healthy” obese (n = 23) were compared with “metabolically healthy” controls (n = 81), the former still showed higher HOMA (p < 0.001), triglycerides (p < 0.05), CRP (p < 0.001) and HbA1c (p < 0.05), higher fibrinogen (p < 0.001), plasma viscosity (p < 0.001), erythrocyte aggregation at 3 s−1 (p < 0.05), but a lower erythrocyte elongation index 60 Pa (p < 0.05). Morbidly obese subjects present a more pronounced altered rheological profile in those with metabolic alterations, although the “metabolically healthy” obese also displayed rheological alterations if compared with “metabolically healthy” non-obese controls. These rheological alterations relate to both insulin resistance and inflammation. Show more

Keywords: Morbid obesity, metabolic syndrome, metabolic alterations, haemorheology

DOI: 10.3233/CH-2011-1417

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 247-255, 2011

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Raynaud de Mauverger, Eric | Mercier, Jacques

Article Type: Research Article

Abstract: While recent studies suggested that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio (WHR) in addition to body index mass (BMI) in assessing the risk of death, this issue remains cintroversial since most authors conclude that BMI explains almost all the obesity-related risk of diabetes and conary heart disease (CHD). We investigated the separate effects of BMI and WHR on blood rheology in 430 patients attending to a metabolic check-up and exhibiting all the spectrum of age (11–77 yr) and BMI (15–50 kg/m2 ). BMI …and WHR are correlated to each other (r = 0.269; p = 0.009) and are both predictors of blood viscosity (BMI: r = 0.15516; p = 0.004; WHR: r = 0.3638; p = 0.03). However while looking at determinants of viscosity these correlations had not the same meaning. For BMI it was explained by its correlation with plasma viscosity (r = 0.17718; p = 0.00105) and red blood cells (RBC) aggregation (all Myrenne and SEFAM indices with r ranging between 0.226 and 0.430) while these parameters were not correlated to WHR. By contrast WHR was strongly correlated with hematocrit (r = 0.524; p = 0.0003) which was not correlated with BMI. A forward stepwise regression selected WRH as a better predictor of blood viscosity, excluding BMI. Thus both BMI and WHR are associated with increased blood viscosity but these correlations reflect separate mechanisms. These data suggest that both overall adiposity and abdominal adiposity induce hyperviscosity, consistent with epidemiological studies linking the risk of CHD to abdominal adiposity and BMI. Show more

Keywords: Adiposity, body mass index, waist-to-hip ratio, hemorheology, erythrocyte deformability, blood viscosity, erythrocyte aggregation

DOI: 10.3233/CH-2011-1418

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 257-263, 2011

Authors: Xia, Y. | Jiang, Y.X. | Dai, Q. | Xiao, Y. | Lv, K. | Wang, L.

Article Type: Research Article

Abstract: Background: The use of the pure blood pool ultrasound contrast agent SonoVue (Bracco, Italy) with specific ultrasound imaging software has enabled the dynamic visualization of tumor microcirculation. Aim: The present study was designed to investigate the washout time of hepatocellular carcinoma (HCC) and correlate it with angiogenesis parameters. Methods: Thirty-one surgically confirmed HCC cases were prospectively evaluated with contrast-enhanced ultrasound (CEUS), and parameters such as wash-in time, peak enhancement time and washout time were determined offline. We also calculated microvessel density and the percentage of microvessel area (MVA) and compared CEUS parameters between a well differentiated group and a poorly …to moderately differentiated group. The Spearman rank order correlation method was used to analyze the relationship between washout time and angiogenesis parameters. Results: The washout time was longer in well differentiated HCC patients compared to those with poorly to moderately differentiated HCC (p < 0.05). In addition, the washout time of HCC was positively correlated with the percentage of MVA (r = 0.510). Conclusions: Given that the percentage of MVA was positively correlated with tumor blood volume, washout time may be associated with HCC blood volume. Show more

Keywords: contrast-enhanced ultrasound (CEUS), hepatocellular carcinoma (HCC), washout time, Angiogenesis

DOI: 10.3233/CH-2011-1420

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 265-273, 2011

Authors: van Genderen, Michel | Gommers, Diederik | Klijn, Eva | Lima, Alex | Bakker, Jan | van Bommel, Jasper

Article Type: Research Article

Abstract: Introduction: Esophagectomy with gastric tube reconstruction is characterized by high postoperative morbidity rates. Recently it was shown that decreased sublingual microvascular blood flow (MBF) preoperatively was associated with increased rate of complications after abdominal surgery. Similar observations in severely septic patients could be treated with dobutamine, independent of cardiac output. Based on these considerations we hypothesized that sublingual MBF derangements are more likely to be found in patients undergoing high risk surgery such as esophagectomy, and if present, might be prevented with administration of low dose dobutamine. Methods: In this single-centre, prospective, double-blinded study, we randomized 20 patients admitted to …the Intensive Care Unit following esophagectomy with gastric tube reconstruction into two groups. The intervention group (D) received a small dose of dobutamine (2.5 μg/kg/min) directly postoperative until two days postoperatively, whereas the placebo group (P) received a similar volume of saline. A subset of patients undergoing pancreaticoduodenectomy surgery was included as control group (C) for comparison with the study group. Sublingual MBF was determined one day prior to surgery until two days postoperatively. Results: At the first postoperative day, patients in the esophagectomy/placebo group (P), showed a significant lower microvascular flow index, perfused vessel density and proportion of perfused vessels compared to baseline (p < 0.001) and the pancreaticoduodenectomy group (C) (p < 0.001). Administration of dobutamine significantly prevented the overall decrease in microvascular blood flow the first postoperative day. Conclusion: Postoperative sublingual MBF is markedly impaired in esophagectomy patients compared to patients who underwent a pancreaticoduodenectomy and could be prevented by early administration of a small dose dobutamine. Show more

Keywords: microcirculation, SDF imaging, esophagectomy, dobutamine

DOI: 10.3233/CH-2011-1421

Citation: Clinical Hemorheology and Microcirculation, vol. 48, no. 4, pp. 275-283, 2011