Clinical Hemorheology and Microcirculation - Volume 39, issue 1-4

Authors: Antonova, Nadia | Riha, Pavel | Ivanov, Ivan

Article Type: Research Article

Abstract: Time variation of whole human blood conductivity and shear stresses were investigated at rectangular and trapezium-shaped Couette viscometric flow under electric field of 2 kHz. The kinetics of conductivity signals were recorded both under transient flow and after the complete stoppage of shearing at shear rates from 0.94 to 94.5 s−1 and temperatures T=25°C and 37°C. Contraves Low Shear 30 rotational viscometer as a base unit and a concurrent measuring system, including a device, developed by the conductometric method with a software for measurement of conductivity of biological fluids (data acquisition system), previously described (IFMBE Proceedings Series, Vol. 11, …2005, pp. 4247–4252; Clin. Hemorheol. Microcirc. 35(1/2) (2006), 19–29), were used for the experiments. The obtained experimental relationships show that the human blood conductivity is time, shear rate, hematocrit and temperature dependent under transient flow. It is also dependent on the regime of the applied shear rates. Non-linear curve approximation of the growth and relaxation curves is done. The results show that valuable information could be received about the kinetics of “rouleaux formation” and the time dependences of the blood conductivity follow the structural transformations of RBC aggregates during the aggregation–disaggregation processes. The results suggest that this technique may be used to clarify the mechanism of dynamics of RBC aggregates. Show more

Keywords: RBC aggregation, blood conductivity, low shear rate viscometry

DOI: 10.3233/CH-2008-1114

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 69-78, 2008

Authors: Arató, E. | Jancsó, G. | Sínay, L. | Kürthy, M. | Lantos, J. | Ferencz, S. | Horváth, S. | Shafiei, M. | Kasza, G. | Verzár, Z. | Kollár, L. | Rőth, E. | Wéber, G. | Menyhei, G.

Article Type: Research Article

Abstract: After revascularization of an acute arterial occlusion the development of a serious ischaemic-reperfusion injury is a menacing challenge and a hard task in peripheral vascular surgery. A whale of evidences point to oxidative stress, as an important trigger, in the complex chain of events leading to reperfusion injury. In the present study authors aimed to examine oxidative stress parameters, antioxidant–prooxidant state and leukocyte adhesion molecules (CD11a and CD18) expression following acute revascularization surgery of lower limb. 10 patients were examined in the prospective randomized study. Peripheral blood sample was collected in ischaemic period, and after reperfusion in the 2nd …and 24th hours, and on 7th day. Superoxide-dismutase activity, reduced glutathion concentration and leukocytes free radical production were measured. The degree of lipidperoxidation was marked with the quantity of malondialdehyde. The expressions of adhesion molecules were measured with flowcytometry. The speed and rate of free radical production significantly increased in the early reperfusion (p<0.05). The level of antioxidant enzymes decreased after revascularization. The CD11a and CD18 expression of the granulocytes significantly (p<0.05) decreased right after the revascularization, but with a gradual elevation until the 7th day they exceed the ischaemic value. Our results showed a time specific turnover of the sensitive antioxidant–prooxidant balance after revascularization operation. Show more

Keywords: Ischaemia–reperfusion, vascular surgery, oxidative stress, reperfusion injury

DOI: 10.3233/CH-2008-1070

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 79-85, 2008

Authors: Katsanos, K. | Moutzouri, A. | Karnabatidis, D. | Siablis, D. | Athanassiou, G.

Article Type: Research Article

Abstract: Iodinated contrast media (CM) are widely used in diagnostic imaging and therapeutic interventional procedures of everyday clinical practice and are associated with multiple hemodynamic and hemorheological effects. The purpose of our work was to investigate the red blood cell (RBC) rheological properties after in vivo administration of low-osmolar or iso-osmolar CM by measuring their membrane deformability (Index of Rigidity, IR) using a filtration method. Blood samples were taken from patients who underwent digital subtraction angiography of the peripheral arteries at various times before and after intravenous administration of CM. CM included iso-osmolar Iodixanol, low-osmolar Iopromide and low-osmolar Iopentol. In the …whole patient group an IR increase of 59% was calculated 5 minutes after administration of CM followed by a normalization of elevated IR values within the following hour. The 5-min IR increase was strongest in the group treated with Iopromide, whereas administration of Iodixanol was associated with a more modest transient IR increase. Intravenous injection of CM in humans may be associated with a transient but considerable decrease of RBC membrane deformability and particularly for the iso-osmolar CM the induced changes in membrane deformability seem to be more moderate. Show more

Keywords: Iodinated contrast media, red blood cell, membrane, deformability, rheology, microcirculation

DOI: 10.3233/CH-2008-1071

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 87-91, 2008

Authors: Aydogan, Sami | Yapislar, Hande | Artis, Seda | Aydogan, Burcu

Article Type: Research Article

Abstract: Impaired red blood cell deformability is a hemorheological perturbation induced by many kinds of diseases. An increase in free radicals causes a reduction in erythrocyte flexibility and deformability. Carnosine is a dipeptide abundant in skeletal muscle and brain of humans. One of the main function of carnosine is its antioxidant and free-radical scavenger effect. In this study our aim is to investigate the protective effect of L-carnosine on RBCs in H2 O2 -induced oxidative stress in vitro conditions. Twenty male wistar albino rats, 10 were 3 months old, 10 were 12 months old used. The blood from each rat …were divided into ten tubes and these blood samples divided into two groups. The first tube of the first group was the control and the rest 4 tubes were treated with different concentrations of L-carnosine. All tubes in the second group were incubated with H2 O2 additively. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). L-carnosine has improved the RBC deformability significantly which is impaired by H2 O2 treatment (p<0.05). Increase in deformability is more significant in young rat group when compared to old rat group. L-carnosine, as an antioxidant molecules, has a dose dependent positive effect on RBC deformability and has improved or protect the deformability of erythrocytes, especially in young rat group which impaired by H2 O2 -induced oxidative stress in vitro conditions. The results of this study first suggest that L-carnosine supplemention can be used to improve the RBC quality or to protect them from oxidative damage in survival of RBC in the circulation. Show more

Keywords: L-carnosine, erythrocytes deformability, oxidative stress, H_2O_2

DOI: 10.3233/CH-2008-1072

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 93-98, 2008

Authors: Birnbaum, J. | Lehmann, Ch. | Klotz, E. | Hein, O. Vargas | Blume, A. | Jubin, F. | Polze, N. | Luther, D. | Spies, C.D.

Article Type: Research Article

Abstract: Introduction: The study's objective was to determine the effects of the administration of N-acetylcysteine (NAC) and of tirilazad mesylate (TM) on intestinal functional capillary density, mesenteric plasma extravasation, leukocyte adherence and on cytokine release during experimental endotoxemia in rats. Methods: In a prospective, randomized, controlled animal study, 80 male Wistar rats were examined in 2 test series. Both series were divided into 4 groups. Group 1 served as control group (CON group). Group 2 (LPS group), group 3 (NAC group) and group 4 (TM group) received endotoxin infusions (10 mg/kg over 2 h). In NAC group 150 mg/kg body …weight NAC was administered after the first 30 minutes of endotoxemia intravenously. In TM group, 10 mg/kg body weight TM was administered after the first 30 minutes of endotoxemia intravenously. Animals of the series 1 underwent studies of leukocyte adherence on submucosal venular endothelium of the small bowel wall and intestinal functional capillary density (FCD) in the intestinal mucosa and the circular as well as the longitudinal muscle layer by intravital fluorescence microscopy (IVM). Plasma levels of interleukin 1β (IL-1β), interferone γ (IFN-γ) and soluble intercellular adhesion molecule1 (s-ICAM 1) as well as white blood cell count (WBC) were estimated. In the animals of the series 2 mesenteric plasma extravasation was determined by IVM and plasma levels of tumor necrosis factor α (TNF-α), IL-4, IL-6, IL-10 and malondialdehyde (MDA) were estimated. Results: After LPS administration, FCD in the villi intestinales was unchanged and in the longitudinal muscularis layer it was increased. There was no effect of NAC or TM administration on FCD. Although the plasma extravasation was not significantly influenced by LPS administration, TM administration resulted in a lower plasma extravasation in the TM group compared to the other groups. After endotoxin challenge, the firmly adherence of leukocytes to vascular endothelium as a parameter of leukocyte activation in endotoxemia was increased but NAC or TM administration had no influence on leukocyte adherence. The plasma levels of IL-1β, IL-6, IL-10, TNF-α, IFN-γ and sICAM-1 were increased in the endotoxemic groups (LPS group, NAC group and TM group) and the WBC was decreased compared to controls. IL-4 levels were unchanged during observation period. Plasma MDA levels were not influenced by LPS administration compared to controls. The administration of NAC resulted in lower sICAM-1 and MDA levels compared to the LPS group. The IL-1β, IL-6, IL-10, TNF-α and IFN-γ plasma levels were not influenced by NAC or TM administration. Conclusions: In this posttreatment sepsis model in rats, NAC administration resulted in lower sICAM-1 and MDA levels compared to the LPS treated animals. TM administration reduced the plasma extravasation in this model. Show more

Keywords: Endotoxin, rat, NAC, tirilazad mesylate, intravital microscopy, intestine, mesentery, perfusion, extravasation, sepsis, cytokines

DOI: 10.3233/CH-2008-1073

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 99-111, 2008

Authors: Cicha, Iwona | Goppelt-Struebe, Margarete | Yilmaz, Atilla | Daniel, Werner G. | Garlichs, Christoph D.

Article Type: Research Article

Abstract: Atherosclerosis results from a combination of local blood flow patterns and systemic risk factors. We investigated whether non-uniform shear stress at bifurcations induces pro-atherogenic endothelial dysfunction and monocyte recruitment. Bifurcating flow-through cell culture slides were used to expose HUVECs to laminar or non-uniform shear stress for 18 h at 10 dyne/cm2 . For the adhesion assay, HUVECs were subsequently perfused with medium containing THP-1 monocytes for 1 h. Protein expression was determined by immunofluorescence. In areas exposed to laminar shear stress, alignment of endothelial cells with the flow was observed, accompanied by upregulation of eNOS and downregulation of connective …tissue growth factor (CTGF). In contrast, cells exposed to non-uniform shear stress near the outer walls of bifurcations were characterized by irregular, unaligned shape, induction of endothelin-1 and CTGF, as well as reduced eNOS expression. These atherogenic effects of non-uniform shear stress were prevented when cells were treated with statins (1 μmol/l) during flow. Under non-uniform shear stress, a slight induction of VCAM-1, ICAM-1, and E-/P-selectin was observed. In agreement with this, monocyte recruitment, which was nearly undetectable under laminar shear stress, was moderately induced by non-uniform shear stress (P<0.02). In conclusion, inhibition of antioxidative eNOS and upregulation of atherogenic proteins is the first step in non-uniform shear stress-mediated endothelial dysfunction, which in vivo in the presence of atherogenic risk factors may further enhance monocyte recruitment into the artery wall. Show more

Keywords: Shear stress, endothelial dysfunction, monocyte adhesion, statins

DOI: 10.3233/CH-2008-1074

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 113-119, 2008

Authors: Clevert, D.-A. | Minaifar, N. | Weckbach, S. | Kopp, R. | Meimarakis, G. | Clevert, D.-A. | Reiser, M.

Article Type: Research Article

Abstract: The purpose of this study was to compare Color Duplex Ultrasound (CDU), Contrast-Enhanced Ultrasound (CEUS) and Multislice Computed Tomography (MS-CT) angiography in the routine follow up of patients following Endovascular Repair (EVAR) of Abdominal Aortic Aneurysm (AAA). 43 consecutive patients with AAA underwent endovascular aneurysm repair and were imaged with CDU, CEUS and MS-CT angiography at regular intervals after the procedure. Each imaging modality was evaluated for the detection of endoleaks. The presence of endoleaks was analyzed and the conspicuity of findings was assessed. CTA was used as gold standard in determining the presence of endoleaks. CDU was …true positive for endoleaks in 5/43 patients (11.6%) and false positive for endoleaks in 2/43 patients (4.6%). The sensitivity of CDU was therefore 33.3% and its specificity 92.8%; the positive and negative predictive values were 0.71 and 0.72, respectively. CEUS was true positive for the detection of endoleaks in 15/43 patients (34.9%) and false positive in 2/43 patients (4.6%). The sensitivity of CEUS was therefore 100% and its specificity 93%; the positive and negative predictive values were 0.88 and 1. In the follow up the two false positive endoleaks in CEUS were confirmed as true positive endoleaks by CEUS and MS-CT. In our small patient group, contrast-enhanced ultrasound seemed to be more accurately in demonstrating endoleaks after EVAR than MS-CT angiography and may be considered as a primary surveillance modality whereas duplex ultrasound scanning alone is not as sensitive as CEUS and MS-CT angiography in detection of endoleaks. Especially in patients with contraindications for CT contrast agents (e.g. due to renal failure or severe allergy) CEUS provides a good alternative to MS-CT. Show more

Keywords: Endoleak, contrast enhanced ultrasound, MS-CT, color duplex ultrasound

DOI: 10.3233/CH-2008-1075

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 121-132, 2008

Authors: Clevert, D.-A. | Graser, A. | Jung, E.M. | Stickel, M. | Reiser, M.

Article Type: Research Article

Abstract: Aneurysms of the extracranial carotid arteries are a rare abnormalitiy and may represent a diagnostic challenge in examination of the patients. B-flow is a new digital vascular ultrasound technique and is an especially reliable method in the diagnosis of the extracranial portion of the internal carotid arteries as it shows less flow artifacts than color-coded Doppler sonography (CCDS) and power Doppler (PD). This review compares color-coded Doppler sonography, power Doppler and B-flow findings in extracranial ICA and CA aneurysm to emphasize the usefulness of B-flow in this clinical condition.

Keywords: B-flow, extracranial carotid artery aneurysm, color-coded Doppler sonography, power Doppler

DOI: 10.3233/CH-2008-1076

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 133-146, 2008

Authors: Clevert, D.-A. | Stickel, M. | Kopp, R. | Weidenhagen, R. | Fink, C. | Jauch, K.W. | Reiser, M.

Article Type: Research Article

Abstract: We report the case of a 61-year-old patient admitted to our hospital owing to recent nonspecific abdominal pain. Five years earlier he had been treated with a graft owing to thoracic and abdominal aortic aneurysm with dissection. He now showed a left renal vein aneurysm with a diameter of 11×7.5 cm. This case demonstrates that contrast enhanced ultrasound (CEUS), employed in addition to computed tomography angiography, offers a promising new option for diagnosis and preoperative treatment planning in patients with abdominal vascular diseases. The results were compared with operative findings.

Keywords: Renal vein aneurysm, AV fistula, abdominal aortic aneurysm, contrast-enhanced ultrasound, abdominal aortic dissection

DOI: 10.3233/CH-2008-1077

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 147-154, 2008

Authors: Clevert, D.-A. | Weckbach, S. | Minaifar, N. | Clevert, D.-A. | Stickel, M. | Reiser, M.

Article Type: Research Article

Abstract: To evaluate the effectiveness of contrast-enhanced ultrasound (CEUS) in the diagnosis and characterization of hepatic, renal and splenic traumatic injuries versus conventional ultrasound (US) and multislice computed tomography (MS-CT). Between January 2005 and January 2007, 78 patients (48 males, 30 females, mean age 56 years) with blunt abdominal trauma were examined by conventional US, CEUS and MS-CT. CEUS employed a low-MI technique using 1.2 to 2.4 ml of SonoVue (Bracco, Italy) i.v. and a multifrequency transducer (2–4 MHz, Siemens, Sequoia, Acuson). CT examinations were performed on a 64 detector CT scanner (Somatom Sensation 16 or 64, Siemens Medical Systems, …Forchheim, Germany) before and after administration of 120 ml intravenous contrast agent (Solutrast® , Bracco, Milan, Italy) followed by 50 ml saline. The presence of hepatic, renal and splenic injuries was analyzed and the conspicuousness of findings was assessed. In 15 of the 78 patients conventional US identified solid organ injuries: 8 hepatic, 2 renal and 5 splenic injuries. CEUS identified 3 more injuries (2 hepatic and 1 splenic) that had been missed by conventional US. CEUS identified traumatic lesions in 18/78 patients. In one of the 18 patients even active bleeding could be identified by CEUS. In CEUS solid organ injuries appeared hypoechoic. MS-CT identified 18 solid organ injuries in 78 patients, corroborating the CEUS results. CEUS greatly improves the visualization and characterization of hepatic, renal and splenic injuries compared to conventional ultrasound and correlates well with MS-CT. The imaging technique detects even minor blood flow and is able to depict vascular structures in detail. At our institution it is used as an additional examination technique which supplements MS-CT in unclear cases. Owing to its bedside availability, CEUS provides a good alternative to MS-CT, especially in patients with contraindications to CT contrast agents (e.g. due to renal failure or severe allergy) and in hemodynamically compromised patients. Show more

Keywords: Trauma, contrast-enhanced ultrasound, multislice computed tomography

DOI: 10.3233/CH-2008-1080

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 155-169, 2008

Authors: Clevert, D.-A. | Minaifar, N. | Weckbach, S. | Jung, E.M. | Stock, K. | Reiser, M. | Staehler, M.

Article Type: Research Article

Abstract: To assess the diagnostic performance of multislice computed tomography (MS-CT) in the classification of atypical or complex cystic renal masses using the Bosniak system in comparison to contrast-enhanced ultrasound (CEUS) and, in unclear cases, to the surgery findings. Thirty-two consecutive patients (14 women, 18 men; age range 39–72 years) with 37 atypical or complex cystic renal masses at MS-CT underwent conventional ultrasound (US) and CEUS. CEUS employed a low-MI technique using 1.6–2.4 ml SonoVue (Bracco, Italy) i.v. and a 2–4 MHz multifrequency transducer (Siemens, Sequoia, Acuson). Fourteen masses were resected, the remaining 23 lesions were followed up for periods …ranging from 3 months to 2 years. Images and digital cine clips of all lesions were evaluated by blinded readers. On the basis of MS-CT appearance the lesions were assigned to the Bosniak classification. Similar criteria modified for US imaging were used to score atypical cysts at CEUS. In the Bosniak classification at MS-CT the lesions were scored as category II (n=15), IIF (n=7), III (n=8) and IV (n=7). At CEUS, masses were classified as Bosniak classification II (n=8), IIF (n=12), III (n=8) or IV (n=9). All type IV and 6/8 type III and 1/8 type IIF lesions were removed surgically. All category IV and 3/8 category III lesions of the surgical group were malignant, the one type IIF lesion was benign. All class II and IIF cysts except one were stable after a follow-up period ranging from 3 months to 2 years. In 7/37 lesions (19%) the MS-CT and CEUS scores were different, while in 30/37 (81%) they were equivalent. CEUS depicted more thin septa than MS-CT, or upgraded wall thickness, resulting in a Bosniak score upgrade from category II to IIF in 5 lesions. Two cystic renal masses could not be clearly assigned by MS-CT but were considered malignant due to the additional information from CEUS, which was confirmed by surgical removal (small cystic renal cancer). CEUS with SonoVue allows an early evaluation of atypical or complex cystic renal masses. It is an additional examination to MS-CT. Due to the dynamic examination, additional information about perfusion of the cystic septa or cystic renal cancer can be gained. Show more

Keywords: Bosniak-classification, contrast enhanced ultrasound, multislice computed tomography

DOI: 10.3233/CH-2008-1083

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 171-178, 2008

Authors: Connes, Philippe | Hue, Olivier | Tripette, Julien | Hardy-Dessources, Marie-Dominique

Article Type: Research Article

Abstract: Sickle cell trait (SCT) is usually considered a benign disorder compared with sickle cell anemia (SS hemoglobinopathy). However, several authors have reported cases of exercise-related sudden death in this population. Among the mechanisms that could be involved in these fatal complications, vaso-occlusive processes, such as those occurring in SS hemoglobinopathy, may play a role. In sickle cell anemia, these vaso-occlusive processes involve inflammatory and adhesion molecules such as the cell adhesion molecules (CAM family), which play a role in the firm adhesion of reticulocytes and leukocytes to endothelial cells, and the selectins, which play a role in leukocyte and …platelet rolling on the vascular wall. Recent results suggest that adhesion phenomena could be amplified in SCT carriers during exercise compared with non-carriers. Other mechanisms like alterations in blood coagulation and/or hemorheological properties can also favor the occurrence of vaso-occlusive processes. Although few studies have reported coagulation disturbances in SCT carriers at rest, we recently observed no difference between this population and control subjects in response to exercise. In contrast, by studying the behavior of several hemorheological parameters in response to several types of exercise, we detected hemorheological abnormalities in individuals with SCT. These abnormalities included higher red blood cell rigidity and higher blood viscosity in the SCT carriers compared with the non-carriers, particularly during the late recovery period (24 and 48 h after exercise). Therefore, we can suggest that the risks for microvascular complications in SCT carriers in response to exercise could be dependent on alterations in blood rheology and vascular adhesion processes. Show more

Keywords: Hemoglobin S, red blood cell deformability, coagulation, selectins, cell adhesion molecules

DOI: 10.3233/CH-2008-1078

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 179-184, 2008

Authors: Leone, Maria Cristina | Gori, Tommaso | Fineschi, Massimo

Article Type: Research Article

Abstract: The coronary slow flow phenomenon (CSFP) is an angiographic finding that is characterised by delayed progression of the contrast medium during coronary angiography. The mechanism of this phenomenon remains unknown. In the present paper, we revise the current evidence regarding this phenomenon and discuss recent findings from our group reporting increased resting resistances in patients with the CSFP. We report that these patients had preserved blood flow responses to the intracoronary infusion of the vasodilator papaverine, demonstrating that the CSFP is not necessarily associated with an abnormal coronary flow reserve. Based on these findings and on the review of …the current literature, we concur with the concept proposed by Beltrame et al. that the CSFP should be considered a separate clinical entity. Further studies are necessary to describe the clinical characteristics, including the prognosis, of these patients and to identify potential treatments. Show more

Keywords: Ischemia, slow flow, microvasculature

DOI: 10.3233/CH-2008-1079

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 185-190, 2008

Authors: Gori, Tommaso | Di Stolfo, Giuseppe | Dragoni, Saverio | Lisi, Monica | Leone, Maria Cristina | Forconi, Sandro | Parker, John D.

Article Type: Research Article

Abstract: Nitroglycerin (GTN) has been shown, in both human and animal studies, to induce a protective phenotype that limits tissue damage after ischemia and reperfusion. This phenomenon is similar to ischemic preconditioning, and several reports suggest that also the molecular pathways involved in this protective effect of nitrates are the same that determine ischemic preconditioning. Our group conducted a series of studies aimed at investigating, using a human model of endothelial IR injury, the mechanism of nitrate-induced preconditioning and particularly the role of reactive oxygen species formation and of the opening of mitochondrial permeability transition pores. Our data demonstrate that …GTN protects the endothelium against postischemic endothelial dysfunction in a mechanism that is mediated by oxygen free radical release and opening of mitochondrial permeability transition pores. In contrast, the protective effect of pentaerithrityl tetranitrate appears to be independent of these mechanisms, and it seems to be mediated by induction of antioxidant genes. Finally, isosorbide mononitrate seems to be devoid of a significant protective effect. These data are summarized and discussed in the present paper. Show more

Keywords: Endothelium, ischemia, reperfusion

DOI: 10.3233/CH-2008-1081

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 191-196, 2008

Authors: Grotti, S. | Gori, T.

Article Type: Research Article

Abstract: Pathophysiological studies have clearly demonstrated that the relationship between endothelial (dys)function and tissue ischemia is bidirectional: while it is well accepted that endothelial dysfunction has a key role in the progression and the instabilization of coronary atherosclerosis, it is also well known that the endothelium is particularly sensitive to ischemia and reperfusion injury, and that this damage is an important component in determining the size of the infarction. Therefore, protecting the endothelium from ischemia has potentially important clinical implications. In this scenario, a particularly important role is played by reactive oxygen species: these elusive mediators are involved in determining the …endothelial toxic effect of risk factors, are involved in reperfusion injury, but, most importantly, also have a role in endothelial preconditioning, a protective process that is characterized by a reduced sensitivity to ischemia and reperfusion. The present paper reports considerations regarding these phenomena as discussed in a lecture at the recent Conference of the European Society of Clinical Hemorheology and Microcirculation held in Dresden, Germany. Show more

Keywords: Oxygen free radicals, ischemia, reperfusion, endothelium, endothelial dysfunction, nitric oxide, ischemic preconditioning

DOI: 10.3233/CH-2008-1082

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 197-203, 2008

Authors: Fink, J. | Fuhrmann, R. | Scharnweber, T. | Franke, R.P.

Article Type: Research Article

Abstract: The aim of this study was to understand the mechanisms of interaction of monocytes/macrophages and foreign body giant cell (FBGC) with implant materials, with respect to the roughness and the solubility of calcium phosphate based coatings. Anderson et al. (Bone Engineering, J.E. Davies, ed., Toronto, 2000, pp. 81–93) showed that the presence of FBGC's and monocytes/macrophages influenced the strength of the implant-tissue integration and that more monocytes/macrophages rested on smooth surfaces compared to rough surfaces. We seeded human bone marrow cells on uncoated ultrasmooth polished TiAl6V4 samples as well as on coated TiAl6V4 discs of the same diameter with two …different calcium phosphates coatings, monetite (DCP) and hydroxyapatite (OHAp), both with rougher surfaces. On uncoated ultrasmooth polished TiAl6V4 discs (UUTi, diameter 16 mm, thickness 2 mm) and on TiAl6V4 discs of same diameter coated with OHAP or DCPA, human bone marrow cells (HMBC) were seeded and cultivated under standard culture conditions for 90 days without addition of inducing substances like ascorbic acid, Na-β-glycerophosphate or dexamethasone. The roughnesses of the virgin samples were assessed with atomic force microscopy and light profilometry. After 90 days of cultivation a fraction of the samples, with cells and extracellular matrix, were stained with hematoxylin eosin (HE) and examined in light microscopy. Ra roughness values of virgin uncoated TiAl6V4 samples were 0.001 μm, of DCP coated discs 4 μm and of OHAp coated discs 3 μm. The examination of HE stained samples showed a high number of FBGC and monocytes/macrophages on the UUTi samples. On the DCP coated samples there were less FBGC and monocytes/macrophages and on the OHAp coated samples we could not find any FBGC and monocytes/macrophages. The extracellular matrix (ECM) we found on the UUTi samples was finer and thinner than on the coated samples. The ECM was vastly spread and not dense on the UUTi samples in contrast to the calcium phosphate coated samples, where the ECM was much thicker and stronger. The ultrasmooth surface of the uncoated TiAl6V4 samples, a material which is accepted to be biocompatible, evidently induced the differentiation of cells of the monocytic lineage and the formation of FBGC out of the cell populations present in the human bone marrow. Show more

Keywords: Calcium phosphate, monocytes, macrophages, foreign body giant cells, stimulation

DOI: 10.3233/CH-2008-1090

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 205-212, 2008

Authors: Fornal, M. | Korbut, R.A. | Lekka, M. | Pyka-Fościak, G. | Wizner, B. | Styczen, J. | Grodzicki, T.

Article Type: Research Article

Abstract: Rheological properties of erythrocytes from patients with high risk of cardiovascular disease (CVD) were analyzed in relation to individual patient risk factors as well as to the medication. Additionally, comparative statistical analysis was performed considering plasma concentration of the selected mediators of vascular endothelium: 6-keto-prostaglandin F1α (PGF1α ), sVCAM-1 and E-selectin adhesion molecules and interleukin-6 (IL-6). It was found that antihypertensive therapy with angiotensin-converting enzyme inhibitor (ACEI) is accompanied by improvement of RBC rheology: the increase of deformability and the decrease of aggregability. This improvement is probably mediated by endothelial prostacyclin and nitric oxide which are generated by ACEI. …A correlation was observed between RBC deformability/aggregability and the patient's hematocrit level, what implicates that the hematocrit level should be explicitly taken into consideration when investigating rheological properties of erythrocytes. A strong relationship was also found between the plasma concentration of sVCAM-1 and patient's age. Show more

Keywords: Erythrocyte deformability, erythrocyte aggregability, hypertension, ACEI, CVD risk

DOI: 10.3233/CH-2008-1084

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 213-219, 2008

Authors: Hiebl, B. | Fuhrmann, R. | Franke, R.P.

Article Type: Research Article

Abstract: Monocytes are broadly discussed in the literature as cells, which can get properties of endothelial progenitor cells after angiogenic stimulation. Angiogenically stimulated monocytes can be used to promote implant vascularisation. A necessity therefore is that these cells can be stored and used after storage without a loose of their characteristic phenotype. In this study we tested, if freshly thawed cryopreserved human monocytes are positive for the mo/macrophage markers CD14 and CD68 and the endothelial marker CD31 after thawing and following angiogenic stimulation in a VEGF-A165 enriched (10 ng/ml) angiogenic medium. Thereby the monocytes were tested before and after differentiation …towards macrophages. The results revealed that freshly thawed human CD14 positive monocytes are positive for CD14, CD68 and CD31 after angiogenic stimulation. This CD specification was much more intense in the differentiated cells. The differentiation step also resulted in an increased cell count. Both results can be attributed to the method of differentiation, were cell culture bags were used instead of common cell culture dishes. Additionally the differentiation medium (X-VIVO 10+10% FCS) was specifically adapted to the requirements of monocytes/macrophages. The study showed that human CD14 positive monocytes can be thawed after cryopreservation without loss of their monocytes/macrophage phenotype and without loss of their ability to get angiogenically stimulated. To enhance the efficiency of both steps (thawing, angiogenic stimulation) it can be useful to differentiate the thawed cells in cell culture bags by the use of X-VIVO 10 (+10% FCS) before angiogenic stimulation. Show more

Keywords: VEGF, monocyte, macrophage, CD14, CD68, CD31

DOI: 10.3233/CH-2008-1086

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 221-228, 2008

Authors: Jovtchev, S. | Stoeff, S. | Arnold, K. | Zschörnig, O.

Article Type: Research Article

Abstract: Covalent binding of poly(ethylene glycol), abbreviated as PEG, to red blood cells (RBC) surface leads to masking of the RBC blood group determinants and the PEG layer on the cell surface sterically hinders RBC–RBC and RBC–plasma protein interactions. We cross-linked linear mPEG-SPA of various molecular mass (2000, 5000, 20000) to washed human RBC under varying incubation ratios polymer to RBC. The electrophoretic mobility (EM) of the modified RBC decreases with increasing of chain length and concentration of PEG up to 50%. It may reflect the alteration in the surface layer thickness and friction. The aggregation behaviour of the pegylated RBC …was studied with the Zeta sedimentation technique modifying the cell–cell interactions pressing them toward each other under centrifugal forces of various magnitudes. As a rule at low centrifugation forces the increase in chain length and concentration of PEG linked to RBC surface reduces the dextran-induced aggregation probably via elevation of the steric repulsion, which counteracts the depletion force generated by the free polymer. This effect was reversed to some extent by elevation of free dextran concentration and centrifugation forces. If cell–cell polymer bridging starts playing a role under these conditions requires further experimental and theoretical investigations. Show more

Keywords: Pegylated red blood cells, aggregation, dextran, Zeta sedimentation ratio

DOI: 10.3233/CH-2008-1085

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 229-233, 2008

Authors: Kaliviotis, Efstathios | Yianneskis, Michael

Article Type: Research Article

Abstract: Red blood cell aggregation affects the flow of blood at low shear rates; not only the behaviour of the fluid deviates from its Newtonian characteristics, but, depending on the shearing history of the flow, the non-Newtonian characteristics may be influenced. It is not clear how the time and flow-dependent characteristics of the microstructural network developed in blood affect its mechanical properties. The present study aims to improve understanding of the effect of dynamic flow conditions on microstructural characteristics and consequently on the mechanical properties of the fluid. Viscosity measurements on blood samples from healthy volunteers (H=0.45) were taken with a …double-walled Couette rheometric cell, under unsteady and quasi-unsteady flow conditions. The aggregation extent index Aα , and the microstructural integrity index AI were assessed with an optical shearing system and image analysis. Results showed that energy losses in Couette geometries may depend on the structural integrity of the developed RBC network. Show more

Keywords: RBC aggregation, shear rate variation with time, microstructural integrity

DOI: 10.3233/CH-2008-1087

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 235-242, 2008

Authors: Késmárky, Gábor | Kenyeres, Péter | Rábai, Miklós | Tóth, Kálmán

Article Type: Research Article

Abstract: Evaluation of plasma viscosity has been underutilized in the clinical practice. Plasma viscosity is determined by water-content and macromolecular components. Plasma is a highly concentrated protein solution, therefore weak protein–protein interactions can play a role that is not characterized by electrophoresis. The effect of a protein on plasma viscosity depends on its molecular weight and structure. The less spheroid shape, the higher molecular weight, the higher aggregating capacity, and the higher temperature or pH sensitivity a protein has, the higher plasma viscosity results. Plasma is a Newtonian fluid, its viscosity does not depend on flow characteristics, therefore it is simple …to measure, especially in capillary viscosimeters. Its normal value is 1.10–1.30 mPa s at 37°C and independent of age and gender. The measurement has high stability and accuracy, thus little alterations may be pathologically important. Inflammations, tissue injuries resulting in plasma protein changes can increase its value with high sensitivity, though low specificity. It can increase in parallel with erythrocyte sedimentation rate (ESR), but it is not influenced by hematocrit (anemia, polycytemia), or time to analysis. Based on these favorable features, in 1942 plasma viscosity was recommended to substitute ESR. In hyperviscosity syndromes plasma viscosity is better in follow-up than ESR. In rheumatoid arthritis, its sensitivity and specificity are better than that of ESR or C-reactive protein. Plasma fibrinogen concentration and plasma viscosity are elevated in unstable angina pectoris and stroke and their higher values are associated with higher rate of major adverse clinical events. Elevation of plasma viscosity correlates to the progression of coronary and peripheral artery diseases. In conclusion, plasma viscosity should be measured routinely in medical practice. Show more

Keywords: Plasma viscosity, erythrocyte sedimentation rate, C-reactive protein, hyperviscosity syndromes, ischemic heart disease, acute phase response

DOI: 10.3233/CH-2008-1088

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 243-246, 2008

Authors: Kirchhof, Kristin | Groth, Thomas

Article Type: Research Article

Abstract: The layer-by-layer technique was used to build-up polyelectrolyte multilayers (PEMs) composed of heparin, an anionic glycosaminoglycan (GAG) and chitosan, a cationic biodegradable polysaccharide on model biomaterial surfaces. The surface coatings shall control adhesion of cells and thus their subsequent proliferation and differentiation. PEMs were characterized physicochemically by static contact angle and quartz crystal microbalance (QCM) measurements. Variations in procedure parameters such as the pH value of the solutions were crucial to the formation process and surface properties in terms of wettability and mass increase. Cell–surface interactions were studied with human fibroblast on PEMs. It was found that the pH value …of solutions had a strong impact on cell adhesion making surfaces extremely cytophobic or moderately cytophilic. Adsorption of fibronectin to the terminal heparin layer could be used to increase cell adhesion in a concentration-dependent manner. Show more

DOI: 10.3233/CH-2008-1089

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 247-251, 2008

Authors: Lamby, P. | Prantl, L. | Gais, S. | Walter, M. | Bachthaler, M. | Nerlich, M. | Feuerbach, S. | Jung, E.M.

Article Type: Research Article

Abstract: Background: A free-flap graft refers to the free transfer of tissue to cover tissue defects caused by trauma or malperfusion in plastic surgery. The basic principle, which makes a free flap working is an adequate blood flow. We applied new techniques which are able to detect the blood flow of the anastomosis and of dermal and subdermal tissue layers in a reliable way. Methods: To this end we applied innovative Ultrasound-techniques (contrast enhanced high resolution Ultrasound (US), color coded Doppler sonography (CCDS), Cross Beam™, Power Doppler, Tissue Harmonic Imaging™ (THI), Speckle Reduction Imaging™ (SRI)), as well as the Indocyanine …Green (ICG) fluorescence angiography to evaluate the vascular integrity of 15 parascapular flaps implanted to the fore foot over a period of four years. The age of the subjects ranged from 16 to 60 years. The US machine (GE Logiq 9) was equipped with a Logiq 9L transducer (6–9 MHz) and the modalities of CHI (Contrast Harmonic Imaging) and True Agent Detection (dual view of B-Mode and contrast mode). Results: The borders of the investigated flaps could be best detected using Cross Beam™ Technology with SRI™ and THI™. Power Doppler was able to detect anastomotic vessels even if they were twisted or elongated. Reduced perfusion curves were seen in cases with low anastomotic flow in CCDS. The CHI™ allowed dynamic flow detection of the microcirculation of the tissue graft over a depth of up to 3 cm including quantitative perfusion curves of tissue microcirculation by using TIC™ analysis. There is a strong correlation between the perfusion indices measured by ICG fluorescence angiography and CHI™. Furthermore the ICG showed a remarkable enhancement of fluorescence in the flap borders, which need to be explored in future investigations. Conclusion: These new applications provide useful and effective methods for improved postoperative monitoring of free flaps in plastic surgery and can lead to substantial reduction in the overall risk of flap failure. Show more

Keywords: Free parascapular flap, fluorescence angiography, ultrasound, contrast enhanced microcirculation

DOI: 10.3233/CH-2008-1094

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 253-263, 2008

Authors: Matschke, K. | Jung, F.

Article Type: Research Article

DOI: 10.3233/CH-2008-1093

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 265-279, 2008

Authors: Mrowietz, C. | Hiebl, B. | Franke, R.P. | Park, J.-W. | Jung, F.

Article Type: Research Article

Abstract: Various radiographic contrast media (RCM) significantly influence the morphology of erythrocytes, especially the formation of echinocytes [Scand. J. Clin. Lab. Invest. 35 (1975), 1–43; Microvasc. Res. 60 (2000), 193–200; Herz 23 (2003), 35–41]. Microscopic studies, however, have shown that these changes of erythrocyte morphology are possibly reversible [Acta Radiol. 37 (1996), 214–217]. The aim of this study was to proof if the RCM-induced echinocyte formation can be reversed by a resuspension in autologous plasma. In this study four RCMs were tested (Iodixanol, Iohexol, Iomeprol and Iopromide). These RCM induced echinocyte formation (after suspension of erythrocytes in plasma/RCM mixtures …for 10 min at 37°C), which was reversible after resuspension in autologous RCM-free plasma (resuspension time 5 min at 37°C). Especially for Iomeprol and Iopromide – the RCMs which induced the strongest echinocyte formation – an echinocyte reduction from 94.2% to 44.5% and for Iopromide from 80.6% to 50.4% occurred. The echinocyte formation was influenced by the type of RCM as well as by the RCM concentration. The same was true for the reversibility of echinocyte formation due to resuspension in autologous plasma (type of RCM: p≤0.0001; concentration of RCM: p=0.0847). Iodixanol was associated with the least numbers echinocytes formed (after suspension in the plasma/RCM-mixture as well as after the resuspension in autologous plasma). A 100% reversibility back to discocytes was observed in none of the RCMs after resuspension in autologous RCM-free plasma. In conclusion, a significant reversibility of RCM-induced echinocyte formation in autologous plasma could be observed. Show more

DOI: 10.3233/CH-2008-1097

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 281-286, 2008

Authors: Leithäuser, B. | Gerk, U. | Mrowietz, C. | Jung, F. | Park, J.-W.

Article Type: Research Article

Abstract: Xantinole nicotinic acid (NA) dose dependently lowers plasma levels of atherogenic lipoproteins and increases blood flow through vasodilation. The aim of this study was to evaluate the effect of NA on cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia. In this open pilot study, five men and three women (74.2±9.1 yrs; 81.4±7.9 kg; 171.6±7.0 cm) with angiographically proven coronary artery disease and hyperlipidemia were included. Nailfold capillary microscopy was used for measurements of erythrocyte velocities at rest and after three minutes of ischemia, before and one hour after intake of 1000 mg of NA. The blood pressure …(120±12/73±8 mmHg vs. 113±10/72±5 mmHg; p=0.19/0.83) and the heart rate (72±8/min vs. 70±7/min; p=0.38) remained unchanged. The mean capillary red blood cell velocity at rest (vRBC ; 0.27±0.23 mm/s vs. 0.32±0.18 mm/s; p=0.089) and the time to maximal post ischemia erythrocyte velocity (tpeak ; 21.0±7.9 s vs. 24.3±15.5 s; p=0.49) did not change. The maximal post ischemic erythrocyte velocity (vmaxRBC ; 0.93±0.33 mm/s vs. 1.19±0.19 mm/s; p=0.0096) raised slightly but significantly, the duration of post-ischemia hyperemia (DpH; 101±16 s vs. 127±15 s; p=0.0005) increased markedly. One patient reported about flush in the whole body. The administration of 1000 mg of NA resulted in a significant improvement of the cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia. Show more

Keywords: Nicotinic acid, coronary artery disease, microcirculation, naifold capillary microscopy, reactive hyperemia

DOI: 10.3233/CH-2008-1091

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 287-292, 2008

Authors: Leithäuser, B. | Zielske, D. | Seyfert, U.T. | Jung, F.

Article Type: Research Article

Abstract: Purpose: The use of clopidogrel is standard in interventional cardiology. Haemorrhage occurs in some patients, which implies a need for a non-transfusional therapy. Desmopressin showed its efficacy as an antidote of acetylsalicylic acid. In this trial the effects of desmopressin on platelet glycoproteins and the platelet's ability to aggregate under the influence of clopidogrel are studied. Methods: The trial was conducted as an open, prospective, single-centre, randomised pilot study with n=17 healthy volunteers in a parallel-group design. 1 h after an oral loading dose of 375 mg clopidogrel the effects of a single-dose of 300 μg of Octostim® …nasal spray (n=9) on platelet aggregation, activity of platelets on the density of membrane-bound receptors are measured. Results: Ristocetin cofactor and platelet reactivity rose significantly after the administration of Octostim® nasal spray with 31.9% and 5.3%, respectively (p=0.0329; p=0.0414). The ADP-induced platelet aggregation increased after the administration of Octostim® nasal spray by approximately 20% (p=0.0564). The fraction of CD62- and CD63-positive platelets did not change after clopidogrel nor after desmopressin (p=0.4203; p=0.6774). The density of GPIIb/IIIa receptors per platelet did not change after desmopressin (p=0.9652). The density of GPIb/IX receptors per platelet rose after desmopressin without reaching the level of significance (p=0.0802). In the desmopressin group alone the receptor density rose by 5.5% (p=0.0783). Conclusion: The administration of desmopressin improved the primary haemostasis when given in addition to a clopidogrel therapy. Patients undergoing a heart catheter procedure with clopidogrel might benefit from the use of desmopressin when having a bleeding episode. Show more

Keywords: Desmopressin, clopidogrel, primary haemostasis, flow cytometry, platelet aggregation

DOI: 10.3233/CH-2008-1092

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 293-302, 2008

Authors: Nash, Gerard B. | Watts, Tim | Thornton, Colin | Barigou, Mostafa

Article Type: Research Article

Abstract: Leukocytes and platelets must adhere to the wall of blood vessels to carry out their protective functions. Rheological factors influencing these processes are the delivery of the cells to the wall, referred to as margination, and the local shear rates and stresses at the wall. Margination requires leukocytes and platelets to be excluded from the central flow of the much more numerous red blood cells. This exclusion may be influenced by red cell aggregation. Red cell aggregation also influences development of plug flow in small vessels, which in turn modifies the wall shear rate and stress from those expected in …ideal Poiseuille flow. Promotion of aggregation by added agents such as high molecular weight dextrans or by reduction in shear rate, increases margination of leukocytes and efficiency of attachment to the vessel wall. Interestingly, however, fewer studies exist for platelets, and these suggest that margination is actually promoted by increasing shear rate. Direct studies of the effects of red cell aggregation on platelets are required, but it appears that aggregation has different effects on delivery of platelets compared to leukocytes. These differences may represent adaptations for efficient adhesion of leukocytes and platelets in different regions of the circulation. Show more

Keywords: Red cell aggregation, leukocyte adhesion, platelet adhesion, margination

DOI: 10.3233/CH-2008-1109

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 303-310, 2008

Authors: Özbek, C. | Mailänder, C. | Schilling, U. | Bach, R.

Article Type: Research Article

DOI: 10.3233/CH-2008-1095

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 311-321, 2008

Authors: Park, J.-W. | Leithäuser, B. | Jung, F.

Article Type: Research Article

Abstract: Introduction: The introduction of phosphodiesterase-5 inhibitors as sildenafil, tadalafil, or vardenafil, has tremendously improved the treatment of erectile dysfunction. Patients with the common comorbidity of cardiovascular disease and erectile dysfunction, however, are at risk for critical hypotension in case of self-treatment of cardiac angina with nitrates after the intake of a phosphodiesterase-5 inhibitor. Methods: We evaluated the safety of 5 mg sublingual nitrendipine after pre-treatment of 8 healthy male volunteers (42.1±9.6 yrs) with 20 mg tadalafil. Randomly four different protocols were compared using six hours blood pressure recordings: (1) baseline, (2) 20 mg tadalafil, (3) 5 mg nitrendipine, and …(4) 20 mg tadalafil+5 mg nitrendipine. Results: The blood pressure was not significantly affected by tadalafil. Nitrendipine lowered the systolic blood pressure significantly by −1.91 mmHg (p=0.0079). The co-medication of 20 mg tadalafil+5 mg nitrendipine lowered the blood pressure significantly by −2.86 mmHg (p<0.0001). There was no statistically significant difference between tadalafil and nitrendipine (p=0.598). Relevant hypotension (systolic blood pressure of <85 mmHg) was observed in none of the study individuals during the four protocols. Conclusions: Sublingual nitrendipine seems to be safe for self-treatment of an anginal attack in patients with stable coronary artery disease, who have taken a phosphodiesterase-5 inhibitor. However, our findings on hemodynamic changes in apparently healthy volunteers have to be confirmed in patients with coronary artery disease. Show more

Keywords: Phosphodiesterase-5 inhibitors, cardiovascular disease, erectile dysfunction, nitrendipine

DOI: 10.3233/CH-2008-1096

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 323-328, 2008

Authors: Schenk, J.F. | Stephan, B. | Zewinger, S. | Speer, T. | Pindur, G.

Article Type: Research Article

Abstract: Genetic polymorphisms in plasminogen activator inhibitor-1 gene-675 4G/5G (PAI-1 4G/5G) are claimed to contribute to an increased risk of venous thromboembolism. Inherited thrombophilia, on the other hand, is associated with the occurrence of spontaneous abortions. The objective of this study was, to explore the significance of genetic polymorphisms of PAI-1 4G/5G with particular emphasis on 4G alleles in pregnant women suffering from venous thromboembolism or early spontaneous abortion, respectively. Therefore genetic PAI-1 4G/5G polymorphisms were studied in 108 pregnant females suffering from venous thromboembolism (n=69) or from spontaneous abortion (<20 week, n=39), respectively. Healthy volunteers (n=238) were taken as controls. …The frequencies of 4G alleles (4G/4G or 4G/5G genotypes) of PAI-1 were significantly higher in venous thromboembolism (OR: 3.40, p=0.0088) and slightly higher, but not significantly, in abortions (RR: 2.33; p=0.1162) compared to controls. The incidence of 4G-carriers in females with abortion was 0.68 (−32%) compared to women suffering from venous thromboembolism alone. We conclude from these data, that the occurrence of PAI-1 4G/4G or 4G/5G genotypes, respectively, is clinically significant for the pathogenesis of venous thromboembolism in pregnancy but not for early abortion. Show more

Keywords: Pregnancy, abortion, venous thromboembolism, genetic plasminogen-activator-inhibitor-1 4G/5G polymorphism

DOI: 10.3233/CH-2008-1098

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 329-332, 2008

Authors: Pongrácz, Endre | Andrikovics, Hajnalka | Bernát, Iván S. | Nagy, Zoltán

Article Type: Research Article

Abstract: Background: The phenotype caracteristic of blood clotting factors are well known, however few data has been documented about effects on haemorheology. The connection among genetic polymorphisms, haemorheological factors and vascular mortality is also studied poorly. Purpose: Our aim was: to study six genetic polymorphisms of blood clotting factors, which presents the role of platelet–plasmaprotein–endothel system in thrombotic course in controls and ischaemic stroke cohort. Second, to study the connection of genotypes and haemorheologic factors and both with five years vascular mortality in patients. Patients and methods: It was studied the genetic polymorhisms of GP IIb/IIIa Leu33Pro, prothrombin gene …G20210A, ACE I/D, fibrinogen gene-455 G/A, Leiden mutation and MTHFR C677T alleles or genotypes in blood samples of 433 ischaemic stroke patients and 173 controls by PCR. Haematocrit values, plasma fibrinogen (FIB) concentration, whole blood viscosity (WBV) at 90 s−1 and also the plasma viscosity (PV) were measured. Vascular mortality of patients were followed during five years and studied by curves Kaplan–Meier. Results: A higher plasma FIB concentration in non smoker patients, carrying A alleles of FIB gene could be observed as compared to wild types (p<0.05). Also a moderate WBV increasing in smoker patients with A alleles was found against wild types (p=0.11), at the same time we observed a significant WBV increasing in non smoker patients (p<0.05). The highest quartile of PV showed a connection with Leiden mutation in whole group of patients (p=0.01), in subgroup of young patients (<50 years) (p=0.03) and also in non smoker groups (p<0.05) as compared to patients having wild types. No association could be detected between different genetic polymorphisms and vascular mortality, however it was observed significant mortality increasing in patients having PV above 1.51 mPa s (p=0.03). Conclusion: Certain genetic polymorphisms of coagulation system could result unfavorable haemorheological changes, however non of them increases the mortality. The connection between higher mortality and PV focuses the attention for the necessity of PV measuring and correction in stroke patients. Show more

DOI: 10.3233/CH-2008-1099

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 333-341, 2008

Authors: Prantl, L. | Schreml, S. | Walter, M. | Kasprzak, P. | Stehr, A. | Nerlich, M. | Feurbach, S. | Jung, E.M.

Article Type: Research Article

Abstract: Purpose: The aim of the prospective study was to evaluate the macro- and microcirculation in the center and periphery of free flaps with high resolution vascular ultrasound. Material: Fifteen patients with free parascapular flaps after lower limb trauma were examined six months postoperative. All ultrasound investigations were performed by one experienced examiner with a multi-frequency linear transducer (5–9 MHz, Logiq 9, GE). Flow evaluation was angle-optimized using digital image technology with the color coded Doppler sonography (CCDS) with measurement of the peak systolic, peak diastolic flow velocities and the resistance index (RI). Contrast harmonic imaging (CHI) with time …intensity curve (TIC) analysis was used for quantitative evaluation of the tissue perfusion. Through a peripheral cubital cannula, a first bolus injection was made of 2.4 ml Sonovue® to evaluate the perfusion near the flap center and the distal part of the flap. Results: The combined analysis of all 15 patients showed in the center and in the periphery of the flap a significant increase (p<0.01; Wilcoxon signed rank test) of the perfusion (relative units = RUs) in the period of 90–120 s after contrast medium application (center: baseline perfusion 2.23±0.31 RUs to 5.25±0.90 RUs after contrast medium; periphery: baseline perfusion 3.07±0.44 RUs to 5.80±0.57 RUs after contrast medium). The separate analysis of the non-bypass group (n=9) and bypass group (n=6) showed a clearly higher central flap perfusion after contrast medium application for the bypass group. The combined analysis of all patients showed RI-values amounting to 0.79±0.03. The RI-values of the bypass group were significantly higher than RI-values of the non-bypass group (p<0.05; t-test; p<0.05; Mann–Whitney rank sum test). Conclusion: The high-resolution ultrasound represents an ideal method for detection of the flow and patency of the bypass and the small vessels of the free flap. The patency of microvascular anastomosis as well as the perfusion and microcirculation in different flap territories and tissue layers can be investigated using dynamic contrast-enhanced ultrasound with subtraction modalities. Show more

Keywords: Free flap, femoral bypass, vascular ultrasound, contrast harmonic imaging (CHI), tissue perfusion

DOI: 10.3233/CH-2008-1100

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 343-350, 2008

Authors: Fehr, Martin | Galliard-Grigioni, Katja S. | Reinhart, Walter H.

Article Type: Research Article

Abstract: We have analysed the influence of acute alcohol exposure in vivo and in vitro on blood flow properties and platelet function. 12 healthy male volunteers drank either 4.36 ml red wine/kg body weight (=0.5 g ethanol/kg) or water at 06.00 p.m. under fasting conditions. Blood was drawn immediately before, and 1, 2, 4 and 13 h after alcohol ingestion. Alcohol had a detectable osmotic effect on erythrocytes; the mean cellular volume (MCV) was significantly smaller 1–4 h after ingestion. Whole blood viscosity remained unaffected, but blood viscosity at a standardized Hct of 45% measured at a high shear rate (94.5 …s−1 ) was increased 2 h after wine ingestion. In the morning, 13 h after wine drinking, platelet aggregation measured with a platelet function analyser PFA-100® was increased to a greater extent than after water drinking. In vitro, no effect was seen when blood was incubated with 0, 12.5, 25, 50 and 100 mmol/l ethanol for 1 h at 37°C. We conclude that an acute exposure to alcohol has only modest effects on hemorheological parameters and platelet aggregation in vivo and no effect in vitro, which suggests that other factors must be involved in both beneficial and harmful effects of wine drinking. Show more

DOI: 10.3233/CH-2008-1102

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 351-358, 2008

Authors: Schade, I. | Knaut, M. | Plötze, K. | Matschke, K.

Article Type: Other

DOI: 10.3233/CH-2008-1103

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 359-362, 2008

Authors: de Oliveira, Sofia | Silva-Herdade, Ana S. | Saldanha, Carlota

Article Type: Research Article

Abstract: The interactions between membrane, peripheral and cytoskeleton proteins are responsible for the maintenance of erythrocyte deformability (EEI) and some of these interactions are modulated by PKC activity. Protein band 3 of the erythrocyte membrane is phosphorylated by phosphotyrosine kinases (PTK) and dephosphorylated by phosphotyrosine phosphatase (PTP). It was previously described by us a signal transduction mechanism that describes a possible pathway connecting an erythrocyte external membrane protein, acetylcholinesterase (AChE), with protein band 3. So how does PKC activity modulate EEI when protein band 3 is phosphorylated or dephosphorylated in absence or presence of AChE effectors? To answer …this we used phorbol 12-myristate 13-acetate (PMA) as an activator and chelerythrine chloride as inhibitor of PKC and also band 3 modulators of band 3 phosphorylation degree, in presence and absence of AChE effectors in order to measure in whole blood samples EEI. Our results showed that erythrocyte deformability was significantly (i) decreased by inhibition of PKC, in absence and presence of AChE inhibitor velnacrine (ii) increased with PMA in absence and presence of ACh and (iii) decreased in presence of calpeptin in absence and presence of either chelerythrine or PMA. These results establish dependence between cytoskeleton proteins, PKC activity, band 3 phosphorylation degrees and EEI. Better understanding of those proteins interactions on transduction mechanisms might trigger possible targets for drug action that would modulate EEI. Show more

Keywords: Erythrocyte protein band 3, protein tyrosine kinases, phosphotyrosine phosphatase, acetylcholinesterase, cytoskeleton, protein kinase C

DOI: 10.3233/CH-2008-1101

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 363-373, 2008

Authors: Artoli, A.M. | Sequeira, A. | Silva-Herdade, A.S. | Saldanha, C.

Article Type: Research Article

Abstract: The recruitment of leukocytes to the endothelial walls is intensively investigated both experimentally and through three dimensional computer simulations. The shear dependent viscosity has been obtained from measured values in post-capillary venules of Wistar rats' cremaster muscle. Localized velocity fields and shear stresses on the surface of leukocytes and near vessel wall attachment points have been computed and discussed for a cluster of recruited leukocytes under generalized Newtonian blood flow with shear thinning viscosity. We have observed one region of maximum shear stress and two regions of minimum shear stress on the surface of the leukocytes close to the endothelial …wall. This suggests that the accumulation of selectins attains a minimum value in two regions, rather than in one region, on the surface of the leukocytes. We have also verified that the collective hemodynamic behavior of the cluster of recruited leukocytes establishes a strong motive for additional leukocyte recruitment. From this study we claim that the influence of the leukocytes rolling on the endothelial wall increases the shear stress on both the leukocyte and the endothelial wall which results in activating more signaling mediators during inflammation. Show more

Keywords: Leukocytes dynamics, intravital microscopy, computational hemorheology, leukocyte wall shear stress

DOI: 10.3233/CH-2008-1105

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 375-380, 2008

Authors: Stoeff, S. | Jovtchev, Sv. | Dikov, I. | Kolarov, D. | Galabova, T. | Trifonova, N. | Hadjieva, Sv. | Mladenova, A. | Lambreva, L. | Penev, M.

Article Type: Research Article

Abstract: Accepted methods of the ESR methodology (the Westergren mode and ZSR mode) and its alternative the plasma viscosity were tested for diagnostic utility in pregnancy induced hypertension and pre-eclampsia. The receiver-operating characteristic curve (ROC) analysis approved moderate diagnostic accuracy for the ESR methodology and supplied support for its preliminary estimated cutoff values but failed to indicate cogent discernment of pathology by values of plasma viscosity. Likely pathological whole blood alterations boost the erythrocyte aggregation while the concomitant depletion of macromolecules degrades plasma viscosity values.

Keywords: Pregnancy induced hypertension, ESR methodology, plasma viscosity, ROC analysis

DOI: 10.3233/CH-2008-1104

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 381-384, 2008

Authors: Vekasi, J. | Koltai, K. | Gaal, V. | Toth, A. | Juricskay, I. | Kesmarky, G.

Article Type: Research Article

Abstract: Hemorheological factors play an important role in the pathogenesis of severe complications of diabetes. The diabetic retinopathy is the leading cause of blindness in patients aged 20–65 years. In our study we investigated the effect of aspirin on the hemorheological parameters in patients with different diabetic retinopathies. Hemorheological parameters (hematocrit, fibrinogen, plasma and whole blood viscosity, red blood cell aggregation) of diabetic patients with non-proliferative (n=14, mean age: 66 years) and proliferative retinopathy (n=8, mean age: 48 years) were measured. The results between the two groups were compared: twelve patients were taking aspirin (group A), while ten patients were …not (group B). Hematocrit, fibrinogen, plasma and whole blood viscosity were significantly higher (p < 0.05–0.001) in patients with diabetic retinopathy who did not take aspirin than in those who took. No significant difference was observed in red blood cell aggregation parameters between the two groups. We could not find any significant difference in the measured parameters between patients with non-proliferative and proliferative diabetic retinopathy. According to our results, all the measured hemorheological parameters were in the pathological range, although aspirin treatment could decrease these factors and thus may help to prevent the progression of severe diabetic retinopathy and perhaps blindness. Show more

Keywords: Diabetic retinopathy, hemorheological parameters, aspirin treatment

DOI: 10.3233/CH-2008-1106

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 385-389, 2008

Authors: Velcheva, I. | Antonova, N. | Titianova, E. | Damianov, P. | Dimitrov, N. | Dimitrova, V.

Article Type: Research Article

Abstract: The aim of the study was to evaluate the possible relationship of the hemorheological disturbances with the clinical symptoms and some risk factors (RF) for cerebrovascular diseases (CVD). The study included 68 patients with CVD, 29 with transient ischemic attacks (TIA) and 39 with chronic unilateral cerebral infarctions (UCI) and 47 healthy control subjects. A questionnaire for RF for CVD was filled. Hemorheological variables: leucocytes, hemoglobin, hematocrit, fibrinogen (Fib), plasma (PV) and whole blood viscosity (WBV) at different shear rates by Couette rotational viscometer Contraves Low Shear 30 were investigated and the hemorheological indices of erythrocyte aggregation (IEA), erythrocyte deformability …(IED) and of oxygen transport to tissues (TO2 ) were calculated. The arterial hypertension was the most frequent RF in the examined patients'. The hemorheological investigation showed significant increase of Fib in the patients with TIA and of PV and WBV in both patients' groups. The comparative study of the hemorheological variables with the RF for CVD showed predominating significant correlations with blood pressure (systolic, diastolic and mean) values, with age, cholesterol, physical activity and the body mass index. Our study confirms the possibility the hemorheological variables to be accepted as RF for development of stroke and for its recurrences. Show more

Keywords: Cerebrovascular disease, hemorheological disturbances, risk factors

DOI: 10.3233/CH-2008-1107

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 391-396, 2008

Authors: Velcheva, I. | Nikolova, G.

Article Type: Research Article

Abstract: The aim of the study was to follow the relationship of the hemorheological variables with the cognitive functions in patients with ischemic cerebrovascular disease (CVD). The patient material comprised 117 patients with CVD, distributed in two main groups: 44 with transient ischemic attacks (TIAs) and 73 with chronic cerebral infarctions (CCI), 48 of them being unilateral (UCI) and 25 bilateral (BCI). Additional relative distribution according to the mean arterial blood pressure (MABP) values or to the presence of pathological asymmetries of the hemispheric cerebral blood flow (CBF) was made. The main hemorheological variables: hematocrit (Ht), fibrinogen (Fib) and plasma viscosity …(PV) were examined. The cognitive functions were assessed with a psychological test battery for evaluation of the general cognitive state, the nonverbal intellect, the episodic memory, the selective attention and the executive functions. The hemorheological investigation revealed predomonant increase of PV. The results of all neuropsychological tests showed significant impairment in the patients with CCI in comparison to TIAs. Fibrinogen correlated best with the psychological parameters. Its increase was associated with disturbance of the nonverbal intellect and the general cognitive capacity in the patients with CCI and BCI. In the presence of lower MABP or lack of pathological asymmetries the correlations of Fib and PV with the psychological scores predominated. The results of our study reveal distinct association between the blood rheological properties and the cognitive functions in the patients with ischemic CVD, which is probably based not only on vascular but also on other nonvascular mechanisms. Show more

Keywords: Cerebrovascular disease, cognitive functions, hemorheological variables

DOI: 10.3233/CH-2008-1108

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 397-402, 2008

Authors: Weinrich, Malte | Stephan, Bernhard | Weiss, Christel | Windischmann, Stefanie | Kopp, Berit | Pindur, Gerhard | Schilling, Martin K.

Article Type: Research Article

Abstract: Introduction: To reduce intraoperative blood loss in liver resections surgical bleeding control is often performed by a complete inflow obstruction of the liver called Pringle manoeuvre leading to a portal venous stasis. Platelet aggregability may be affected by this circulatory stasis. Materials and methods: A study population of 11 patients (37–67 years old, 7 females and 4 males) with hepatic tumours underwent elective liver resection. Pringle manoeuvre of up to 50 min duration was used in 4 patients. The other 7 patients were operated using selective vascular clamping. Platelets were aggregated before and after liver resection with adenosine diphosphate, …collagen and ristocetin (according to Born). Results: Mean maximal amplitudes of platelet aggregation were comparable before and after liver resection. Statistic analysis did not detect a significant difference between the values before and after liver resection as well as between Pringle manoeuvre and selective vascular clamping. Conclusion: Induced platelet aggregability is not affected by the method of surgical bleeding control used in liver resection. Platelet aggregability seems to be resistant even to portal venous stasis of up to 50 min during Pringle manoeuvre. Show more

Keywords: Induced platelet aggregation, Pringle manoeuvre, selective vascular clamping

DOI: 10.3233/CH-2008-1110

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 403-408, 2008

Authors: Weinrich, Malte | Scheingraber, Stefan | Stephan, Bernhard | Weiss, Christel | Kayser, Anna | Kopp, Berit | Schilling, Martin K.

Article Type: Research Article

Abstract: Introduction: Measurement of central venous oxygen saturation has become a surrogate parameter for fluid administration, blood transfusions and treatment with catecholamines in (early) goal directed therapy in the treatment of acute septic patients. These strategies are not easily transferred to the postoperative management of abdominal surgery due to the different conditions in surgical patients. Materials and methods: A study population of 15 patients (8 females/7 males) underwent elective major abdominal surgery: 6 gastrectomies, 5 major liver resections and 4 lower anterior rectum resections. Surgery was performed for primary or secondary malignancy. The patients' age was 65.4±12.7 (mean±standard deviation, range …44–84, median 62) years. Blood samples were taken intraoperatively from indwelling central venous lines as well as from draining veins at the surgical site. Blood gas analyses to determine the oxygen saturations were performed immediately. All patients were operated in standardized general anesthesia including epidural analgesia and in a balanced volume status. Results: Central venous oxygen saturations and oxygen saturations in blood from the draining veins of the surgical site showed a wide range with high intra- and interindividual differences intraoperatively. Overall, at most time points no correlation between the two oxygen saturations could be detected in three operation types. A significant correlation was only observed at one time point during liver resections. Conclusion: Our results show a lack of correlation between central venous oxygen saturations and oxygen saturations in the draining veins of the surgical site during major abdominal surgery. Measurement of central venous oxygen saturations does not seem to be a good surrogate for the local oxygen supply in the field of interest in major abdominal surgery even under standardized conditions. Show more

Keywords: Central venous oxygen saturation, venous oxygen saturation at the surgical site, local venous oxygen saturation, major abdominal surgery

DOI: 10.3233/CH-2008-1111

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 409-415, 2008

Authors: Wenzel, F. | Baertl, A. | Zimmermann, N. | Hohlfeld, Th. | Giers, G. | Oldenburg, J. | Assert, R.

Article Type: Research Article

Abstract: Introduction: Biomarkers reflecting an inflammatory or immunological response are increasingly offered to improve the risk stratification of patients. For example, current evidence suggests that soluble CD40 ligand (sCD40L) is elevated in patients with acute coronary syndrome. But only a few data are available to evaluate the influence of preanalytic conditions on sCD40L values. Methods: Blood samples of seven healthy blood donors were collected in tubes without additives and in EDTA- or citrate-filled tubes at various storage conditions. Platelet count was modified by serum dilution, and sCD40L was measured in platelet-rich-plasma and in whole blood. sCD40L levels were determined by …an commercially available ELISA-Kit. Results: Immediately after blood sample assessment, sCD40L levels in serum samples were elevated (1258±820 pg/ml) compared to EDTA (64±32 pg/ml) and citrate (60±8.5 pg/ml) values. Additionally, sCD40L levels were dependent on storage duration. After platelet activation, sCD40L levels were significantly increased to 8278±2453 pg/ml and were significantly correlated to platelet count (r=0.96). Conclusions: Soluble CD40L levels were clearly influenced by preanalytical conditions and were dependent on storage duration, sample technique and platelet count. These influences should be considered by the determination and evaluation of sCD40L concentrations. Show more

Keywords: Soluble CD40L, preanalytical conditions, platelet count, serum samples

DOI: 10.3233/CH-2008-1112

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 417-422, 2008

Authors: Yerer, Mükerrem Betül | Aydoğan, Sami | Çomu, Faruk Metin

Article Type: Research Article

Abstract: Alterations in erythrocyte mechanical activities under the influence of anesthesia have been observed and discussed among the responsible factors for the deterioration of tissue and organ perfusion related to anesthetic procedures. 21 female and 17 male Swiss Albino rats were used. Female (f) and male (m) rats were divided into 3 groups; control (f (n=7); m (n=5)), sevoflurane treated group (f (n=7); m (n=5)), desflurane treated group (f (n=7); m (n=7)). 2% of sevoflurane or 6% desflurane were applied to the rats with inhalation in an adjustable cage for one hour. The deformability indexes of the erythrocytes were measured …by a laser diffractometer (Myrenne Rheodyne SSD). Sevoflurane anesthesia has improved the deformability of erythrocytes in male rats (p<0.05) whereas there were not any significant changes in female rats. Desflurane has improved the deformability of erythrocytes in both gender significantly (p<0.05). Volatil anesthetic agents sevofluran and desflurane has improved the mechanical properties of the erythrocytes in male rats compared to their controls. However, these changes were not significant with sevoflurane in females. The results in male rats may be due to the effects of testosterone on the flexibility of the erythrocytes leading them to tolerate to the environmental changes. These results reveal that the inhalation anesthetics like sevoflurane and desflurane are appropriate anesthetics which can improve the deformability of erythrocytes during surgery. Show more

Keywords: Sevoflurane, desflurane, anesthesia, erythrocyte deformability, rats

DOI: 10.3233/CH-2008-1113

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 423-427, 2008

Article Type: Other

Citation: Clinical Hemorheology and Microcirculation, vol. 39, no. 1-4, pp. 429-435, 2008