Clinical Hemorheology and Microcirculation - Volume 49, issue 1-4

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Cassan, Delphine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: Athletes involved in rugby are characterized by a very specific pattern of body composition with an unusually important muscle mass. In a preceding study about rugbymen we evidenced that they exhibit a correlation between red blood cell aggregability and the amount of body fat although it remains within a normal range, and that red cell rigidity was correlated to isometric adductor strength. We had the opportunity of studying the relationships among exercise performance, body composition and hemorheology in 19 female rugby players (age 19–26, mean: 24.47 ± 0.67 yr) practising 4 – 10 hr/wk (mean 7.15 ± 0.3) since 1–12 …yr (mean 4,05 ± 0,694). VO2max was not related by its own to blood rheology, either hematocrit (r = −0.0717 p = 0.7706) or plasma viscosity (r = 0.0144; p = 0.9533), but other markers of performance exhivited a correlation with red cell rheology. Relationships between fitness and body composition were evidenced. Isometric handgrip strength was negatively correlated to red blood cell aggregability (Myrenne M, r = −0.57839; p = 0.00948 M1 r = −0.58910; p = 0.00795). Adductor isometric strength was negatively correlated to red blood cell aggregability Myrenne M (r = −0.5033; p = 0.0280) but not to M1 (r = −0.4227; p = 0.0714). Fat mass is a major determinant of the maximal oxygen consumption VO2max either measured by a field test (r = −0.766; p = 0.00013) or exercise test (r = −0.575; p = 0.00994) and was also negatively correlated to both handgrip (r = −0.4918; p = 0.0325) and RBC aggregability M (r = −0.57839; p = 0.00948 and M1 r = −0.5891; p = 0.00795). Independently of fat mass, FFM appears to be a determinant of blood viscosity (r = 0.4622; p = 0.0463) due to its correlation with RBC rigidity (r = 0.4781; p = 0.0384). Thus, trained young women exercising 4–10 hr/wk and thus exhibiting a low percentage of body fat exhibit clear relationships between body composition and hemorheology, but fat mass being low, the parameter correlated with blood rheology is in this case fat-free mass, consistent with recent findings indicating that high fat mass in women is sometimes correlated with parameters of the metabolic syndrome such as insulin resistance or inflammation. In addition, parameters quantifying fatness even within such a physiological range are in this sample negatively related with exercise performance. Show more

Keywords: Rugby, exercise, fat mass, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation

DOI: 10.3233/CH-2011-1470

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 207-214, 2011

Authors: Brun, Jean-Frédéric | Varlet-Marie, Emmanuelle | Fédou, Christine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: Aerobic capacity and performance are associated with increased blood fluidity, while sedentarity leads to decreased exercise performance, and blood hyperviscosity. We aimed at investigating the relationships among body composition, blood rheology and exercise performance in this situation. In 46 sedentary subjects (53.09 ± 1.79 yr old; BMI = 32,35 ± 0,80) attending our unit for an exercise prescription we performed an exercise test to assess aerobic capacity, together with blood lipid profile and blood viscosity (MT 90 viscometer, Myrenne erythroaggregometer). The maximal aerobic capacity VO2max was not correlated to blood rheology but its changes were negatively correlated to those …of plasma viscosity (r = −0.679) and pre-training VO2max values were negatively correlated to the BMI (r = −0.45873; p = 0.00430) and fatness (waist circumference r = −0.53476; p = 0.00406). Hemorheological parameters were as expected correlated to blood lipids. The main determinant of the RBC rigidity index Tk was HDL-cholesterol (r = −0.70026; p = 0.00121). The main determinant of M1 is HDL-cholesterol (r = −0.5157; p = 0.0238). RBC aggregability “M” is negatively correlated to total cholesterol (r = −0.758932; p = 0.000105); HDL-cholesterol (r = −0.62232; p = 0.00444); LDL-cholesterol (r = −0.64486; p = 0.00386). Whole blood viscosity is correlated to triglycerides (r = 0.8569; p = 0.00000140) and negatively correlated to HDL-cholesterol (r = −0.5622; p = 0.0122). Waist circumference (an index of abdominal fatness) is correlated to blood viscosity (r = 0.597; p = 0.00888). The waist to hip ratio is correlated to Hct (r = 0.70075 p = 0.00120) and to blood viscosity (r = 0.8124334; p = 0.0000420). Fat-free mass is correlated to blood viscosity (r = 0.66528; p = 0.00137) and hematocrit (r = 0.64350; p = 0.00220). Hip circumference is negatively correlated to plasma viscosity (r = −0.5007; p = 0.0290). Therefore, this study confirms that hemorheological parameters are influenced by blood lipids, that changes in plasma viscosity are correlated to those of aerobic capacity, and that abdominal fat mass is associated with a worsening of blood rheology and of exercise performance. By contrast, gluteal fat (a factor associated with favorable lipid profile and high insulin sensitivity) is associated with a decrease in plasma viscosity, and fat-free mass is associated with higher blood viscosity and hematocrit, consistent with recent literature linking its size in abdominal obesity with a deleterious metabolic profile. Show more

Keywords: Metabolic syndrome, body fluids, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation, fat mass, fat-free mass, gluteal fat

DOI: 10.3233/CH-2011-1471

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 215-223, 2011

Authors: Varlet-Marie, Emmanuelle | Brun, Jean-Frédéric | Fédou, Christine | Raynaud de Mauverger, Eric

Article Type: Research Article

Abstract: The aim of this study was to assess on a large series of soccer players our previous reports on blood rheology and exercise performance. In 99 soccer players (Age 24,17 ± 0,42 yr; weight 75,87 ± 0,89 kg; VO2 max 46,86 ± 0,95 mL/min/kg) an exercise test was performed for measuring maximal aerobic capacity and we measured blood viscosity at high shear rate (MT90 viscometer) and RBC aggregation (Myrenne MK1). The French questionnaire developped by the consensus group on overtraining of the French Society of Sports Medicine (SFMS) was also employed. The only hemorheologic statistical determinant of VO2 max was …hematocrit (Hct r = −0.2439; p = 0.0303). The lactate threshold 2 mmol/l was negatively correlated to M1 (r = −0.43224; p = 0.00847). There was a borderline correlation between the overtraining score at the questionnaire of the SFMS and plasma viscosity (r = 0.3080; p = 0.0532). Therefore, our study confirms that aerobic capacity in this sport is negatively correlated to hematocrit, that RBC aggregation is positively associated with blood lactate accumulation in blood during exercise, and that plasma viscosity is one of the parameters that increase when the athlete is on the edge of the overtraining syndrome. These data are consistent with previous reports about soccer players but caution is needed to extrapolate to other sports. Show more

Keywords: Exercise, soccer, overtraining, hematocrit, blood viscosity, plasma viscosity, hemorheology, erythrocyte aggregation

DOI: 10.3233/CH-2011-1472

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 225-230, 2011

Authors: Simmonds, Michael J. | Tripette, Julien | Sabapathy, Surendran | Marshall-Gradisnik, Sonya M. | Connes, Philippe

Article Type: Research Article

Abstract: Background: The principal determinants of oxygen uptake ($\Vdot$O2 ) kinetics are controversial, with dynamic changes in central and peripheral factors mediating oxygen supply and utilisation suggested to be limiting. The aim of this study was to determine whether important parameters of blood rheology were related to the exercise-induced time-course changes in $\Vdot$O2 and cardiac output ($\Qdot$c), or steady-state arteriovenous oxygen difference (a-vO2 D) during submaximal cycling. Methods and Results: Blood was collected from ten healthy, recreationally active males and females (age: 21.7 ± 1.3 yr; body mass index: 22.7 ± 2.0 kg·m−2 ), before each subject cycled at 105% …of the first ventilatory threshold. Red blood cell aggregation was negatively correlated with steady-state $\Vdot$O2 during exercise and the a-vO2 D at rest (r = −0.73, p < 0.05), and positively correlated to $\Qdot$c at rest (r = 0.71, p < 0.05). Blood viscosity at various shear rates was negatively correlated with the time constant of $\Vdot$O2 (all p < 0.01) on-transient kinetics. Red blood cell deformability at various shear stress was positively correlated to the time constant of $\Vdot$O2 (all p < 0.05) on-transient kinetics. Conclusions: The findings of the present study suggest that the rheological properties of blood may modulate, at least in part, the rate of change in the uptake and/or utilisation of oxygen at the onset of exercise. Show more

Keywords: Aggregation, blood viscosity, deformability, oxygen uptake kinetics, red blood cell

DOI: 10.3233/CH-2011-1473

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 231-241, 2011

Authors: Jung, F. | Leithäuser, B. | Sternitzky, R. | Mrowietz, C. | Pindur, G.

Article Type: Research Article

Abstract: Background: Endothelial cells secrete different mediators depending on biochemical and/or biophysical conditions, which can lead to vasodilation or vasoconstriction, respectively. Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. Material and methods: In order to examine, whether such macrocirculatory data might correlate with data obtained in the supplied microvessels, a parallel investigation in the brachial artery (BA) and the supplied nailfold …capillaries was performed. The duration and amplitude of the postischemic hyperemia (stasis in the vasculature of the left arm using a blood pressure cuff for 3 minutes) were measured (ultrasound technique) and simultaneously the amplitude and duration of the postischemic hyperemia in ipsilateral nailfold capillaries (intravital capillaroscopy). Results: There was absolutely no correlation between the duration (n = 153, r = 0.076, p = 0.3493) of the diameter increase in the BA and in ipsilateral nailfold capillaries. Conclusion: The regulation of the cutaneous microcirculation did not follow diameter changes of the conduit artery (BA) but seems to be dominated by the precapillary arterioles. Show more

Keywords: Conduit artery, microcirculation, cutaneous capillaries, endothelial dysfunction

DOI: 10.3233/CH-2011-1474

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 243-250, 2011

Authors: Prantl, L. | Pfeifer, C. | Geis, S. | Gosau, M. | Jung, E.M.

Article Type: Research Article

Abstract: Purpose: Osteocutaneous free flaps (OFF) are widely used to reconstruct large bone defects in trauma and cancer surgery. Currently no monitoring method is available to detect blood circulation around and inside the bone after transplantation. Therefore we used for the first time contrast-enhanced high-resolution ultrasound (hrCEUS) to gain evidence for the microcirculation of the transplanted bone. Materials and methods: 15 patients transplanted with OFF because of large bone defects at different sites were examined postoperatively with hrCEUS with a high resolution linear probe (6–9 MHz, LOGIQ E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue® , Bracco, …Italy). Operation and examination were performed by either an experienced plastic surgeon or an experienced ultrasound examiner. Microcirculation of the periost and bone was analyzed in different regions of interest (ROIs) and quantitative microcirculation analysis was performed using time intension curve analysis (TIC). We further analyzed clinical outcome of the patients in respect to revision-surgery, necrosis of the OFF and flap survival as well as viability on standard x-rays 2 months after surgery. Results: The most representative parameter by TIC analysis of hrCEUS were the area under the curve (AUC) and the time to peak (Ttop). The AUC of the periost and central part of the bone showed a high correlation (Pearson's r = 0.831). Mean AUC for the periost was 163.92 dB ± 49.44 and for the central part of the bone 70.42 dB ± 25.33. The Ttop of the periosteal ROI was 33.04 sec. ± 6.71 and the bone ROI 41.01 sec. ± 9.24. There was a high correlation of the Ttop of the periost and bone (Pearson's r = 0.937). One revision had to be performed due to haematoma and microcirculation defect of the distal part of the transplanted bone graft which was detected early by hrCEUS and the distal part of the avital bone could be removed timely. Conclusion: For the first time we could show that hrCEUS is a reliable method to evaluate the viability of OFF. The AUC and Ttop seem to be a valuable parameter to detect the microcirculation around and inside the bone transplant. Show more

Keywords: Bone transplant, contrast-enhanced ultrasound, TIC analysis, microcirculation

DOI: 10.3233/CH-2011-1475

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 251-259, 2011

Authors: Damaske, Ana | Muxel, Selina | Fasola, Federica | Radmacher, Marie Christine | Schaefer, Sarina | Jabs, Alexander | Orphal, Dörte | Wild, Philipp | Parker, John D. | Fineschi, Massimo | Munzel, Thomas | Forconi, Sandro | Gori, Tommaso

Article Type: Research Article

Abstract: The slow coronary flow phenomenon (SCF), a condition described by the presence of inappropriate delay in the progression of intracoronary contrast during angiography in the absence of stenoses, has been shown in some patients presenting with chest pain. While several conditions leading to “secondary” slow flow are known, there are no definitive conclusions regarding the exact pathogenesis of “primary” SCF. The present paper outlines the mechanisms that may lead to SCF, emphasizing the role of hemorheological and vascular factors in the pathogenesis of this phenomenon. Small vessel dysfunction has been proposed in the pathogenesis of SCF since the first description …of this syndrome in 1972. Abnormalities in coronary microvascular function result from increased microvascular resistances and impaired endothelial release of vasoactive substances, especially in production and bioavailability of endothelium derived NO. Inflammatory conditions (increased levels of C-reactive protein, interleukin-6 and adhesion molecules) and metabolic abnormalities such as impaired glycemic control, hyperuricemia and elevated serum gamma-glutamyltransferase were also found to contribute to microvascular dysfunction in patients with SCF. New studies have also indicated that increased blood viscosity and one of its major determinants, erythrocyte aggregation, is associated with the SCF. Rheological variables play a role in the control of shear stress and contribute to blood flow velocity changes. Although platelets do not have a significant influence on blood viscosity, it has been demonstrated that they are involved in the development of SCF. Increased mean platelet volume (MPV), an indicator of platelet activation and platelet aggregability is also significantly higher in patients with SCF compared with patients with normal coronary flow. Show more

Keywords: Coronary slow flow, endothelial function, viscosity, hematocrit, platelets

DOI: 10.3233/CH-2011-1476

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 261-269, 2011

Authors: Abegunewardene, Nico | Schmidt, Kai-Helge | Vosseler, Markus | Kreitner, Karl-Friedrich | Schreiber, Laura M. | Lehr, Hans-Anton | Gori, Tommaso | Münzel, Thomas | Horstick, Georg

Article Type: Research Article

Abstract: Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. …Wall thickness at end-systole (6.8 mm vs. 5.9 mm, p < 0.001) and at end-diastole (5.4 mm vs. 4.2 mm, p < 0.001) were significantly higher in the therapy group. Additionally, the regional wall motion at the level of the ischemic region was 3.5 mm in the therapy group while it was significantly less (3.0 mm, p < 0.001) in the control group. Conclusions: Our findings demonstrate that transient iNOS overexpression potentially leads to a significant decrease of regional late enhancement with a positive effect on regional cardiac function in the ischemic area in a large animal model of postischemic heart failure. Show more

Keywords: iNOS, gene therapy, regional contractility, heart failure

DOI: 10.3233/CH-2011-1477

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 271-278, 2011

Authors: Lechler, Philipp | Klein, Silvan M. | Prantl, Lukas | Englert, Carsten | Renkawitz, Tobias | Grifka, Joachim

Article Type: Research Article

Abstract: Both, skeletal development and fracture healing depend on an orchestrated sequence of cellular growth and differentiation processes. Regional changes in tissue oxygen tension were proposed as key regulators of osteoblast proliferation and phenotype. Hypoxia results in the stabilization of hypoxia-inducible factor-1α (HIF-1α), thus influencing expression of a multitude of genes required for cellular adaptation. In the present study we dissected the effects of HIF-1α on cellular proliferation and gene expression of primary human osteoblasts. Primary human osteoblasts were studied by transfecting siRNA and plasmids coding for human HIF-1α. Gene expression was analyzed by western blot and quantitative PCR. Functional assays …were performed to study HIF-1α function, i.e. proliferation and cell cycle analysis. As previously reported exposure to hypoxia led to a stabilization of HIF-1α on protein level and resulted in reduced rates of proliferation and osteocalcin expression. Furthermore, the expression of the proproliferative gene survivin was significantly reduced (p < 0.01). Knock down of HIF-1α attenuated hypoxic downregulation of proliferation (p < 0.05), and osteocalcin (p < 0.05) as well as survivin (p < 0.05) expression significantly. Importantly, the isolated overexpression of HIF-1α impaired proliferative activity and led to significantly reduced rates of expression of osteocalcin (p < 0.05) and survivin (p < 0.01). The present study shows that HIF-1α might reduce proliferation and survivin expression in primary human osteoblasts independently from cellular hypoxia. Furthermore, HIF-1α promoted the loss of the characteristic osteoblastic marker, osteocalcin in vitro. These findings underline the important role of HIF-1α in bone physiology and pathophysiology. Modulating HIF-1α function in hypoxic environments could be of value for future therapeutic approaches. Show more

Keywords: Hypoxia, HIF-1alpha, osteoblast, proliferation, cell viability

DOI: 10.3233/CH-2011-1478

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 279-286, 2011

Authors: Luca, Mary Clare | Liuni, Andrew | Muxel, Selina | Münzel, Thomas | Forconi, Sandro | Gori, Tommaso | Parker, John D.

Article Type: Research Article

Abstract: Despite decades of research and thousands of experimental publications, acute preconditioning strategies have yet to be implemented in clinical practice. While some have attributed this to a failure of the experimental studies to mimic the clinical environment, others have suggested that acute preconditioning strategies themselves may possess physiological limitations. In particular, there is evidence to suggest a reduced efficacy of acute preconditioning in the aged heard and in disease states, such as diabetes, hypertension, hyperlipidemia, and atherosclerosis. In addition, pharmacologic agent commonly used in clinical practice, such as sulfonylureas and non-steroidal anti-inflammatory agents may interfere with acute preconditioning signaling pathways. …Such considerations may preclude the translation of acute preconditioning strategies to the clinical setting. This has led some to shift attention to alternate strategies of cardioprotection, one such strategy being the possibility of generating a prolonged state of cardioprotection. Although preliminary, studies to date have suggested that sustained preconditioning strategies may not be associated with the same drawbacks as acute preconditioning. Further, cardioprotective signaling pathways that elicit the sustained preconditioning response may be distinct from acute signaling pathways, which permit pharmacologic targeting of these pathways in the future. Additionally, sustained preconditioning strategies may be clinically applicable in the setting of acute myocardial infarction, a setting where acute preconditioning strategies are inherently limited. This review will briefly discuss the current data regarding sustained preconditioning strategies, including those in humans, and discuss the goal of future studies in this setting. Show more

DOI: 10.3233/CH-2011-1479

Citation: Clinical Hemorheology and Microcirculation, vol. 49, no. 1-4, pp. 287-293, 2011