Clinical Hemorheology and Microcirculation - Volume 63, issue 3

Authors: Jung, Christian | Jung, Friedrich | Kelm, Malte

Article Type: Editorial

Abstract: In the past years the microcirculation has gained increasing attention not only by basic scientists, but also by clinicians and translational researchers. In the clinical scenario, it has been convincingly described that the microcirculation is a key predictor of outcome and of central pathophysiological relevance. A vast body of evidence demonstrates the central role of the smallest vessels in inflammation, hyperviscosity, cell-cell-interaction, endothelial function, tissue edema, hemodynamic and blood flow regulation and its important role in the interaction with soluble factors. A central feature of different diseases and a strong regulator of different changes is hypoxia, the lack of oxygen. …Also the microcirculation is on one hand a central component responding with dynamic changes to hypoxia but also the central place where hypoxia mediates its unfavorable effects. These changes and associated interactions are the topic of this special thematic issue “Hypoxia” in Clinical Hemorheology and Microcirculation and it seems logical that important and relevant findings are presented. Show more

Keywords: hypoxia, microcirculation, perfusion, oxygen, vessels

DOI: 10.3233/CH-1663301

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 169-172, 2016

Authors: Brinkmann, C. | Bizjak, D.A. | Bischof, S. | Latsch, J. | Brixius, K. | Bloch, W. | Grau, M.

Article Type: Research Article

Abstract: This study examines the effects of endurance training on red blood cells (RBC) in seventeen non-insulin-dependent type 2 diabetic men with a special focus on in vivo RBC aging. Venous blood was collected pre- and post-training at rest. RBC from whole blood and RBC separated according to cell age by density-gradient centrifugation were analyzed. RBC deformability was measured by ektacytometry. Immunohistochemical staining was performed to quantify the RBC-nitric oxide (NO) synthase activation (RBC-NOSSer1177 ) because RBC-NOS-produced NO can contribute to increased RBC deformability. The proportion of “young” RBC was significantly higher post-training. RBC deformability of all RBC (RBC of …all ages) remained unaltered post-training. During RBC aging, RBC deformability decreased in both pre- and post-training. However, the training significantly increased RBC deformability in “young” and reduced their deformability in aging RBC. RBC-NOS activation remained unaltered in all RBC post-training. It tendentially increased in aging RBC pre-training, but did not change during aging post-training. The training significantly reduced RBC-NOS activation in “old” RBC. Endurance training may improve the RBC system (higher amount of “young” RBC which are more deformable). It remains speculative whether changes in older RBC (reduced RBC-NOS activation and deformability) could lead to more rapid elimination of aged RBC. Show more

Keywords: Erythrocytes, T2DM, RBC deformability, nitric oxide, NO

DOI: 10.3233/CH-151957

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 173-184, 2016

Authors: Grau, Marijke | Kollikowski, Alexander | Bloch, Wilhelm

Article Type: Research Article

Abstract: Remote ischemia preconditioning (rIPC), short cycles of ischemia (I) and reperfusion (R) of a region remote from the heart, protects against myocardial I/R injury. This effect is triggered by endothelial derived nitric oxide (NO) production. Red blood cells (RBC) are also capable of NO production and it is hypothesized that the beneficial effect of rIPC in terms of cardioprotection is strengthened by increased RBC dependent NO production and improved RBC function after rIPC maneuver. For this purpose, twenty male participants were subjected to four cycles of no-flow ischemia with subsequent reactive hyperemia within the forearm. Blood sampling and measurement of …blood pressures and heart rate were carried out pre intervention, after each cycle and 15 min post intervention at both the non-treated and treated arm. These are the first results that show improved RBC deformability in the treated arm after rIPC cycles 1– 4 caused by significantly increased RBC-NO synthase activation. This in turn was associated to increased NO production in both arms after rIPC cycles 3 + 4. Also, systolic and diastolic blood pressures were decreased after rIPC. The findings lead to the conclusion that the cardioprotective effects associated with rIPC include improvement of the RBC-NOS/NO signaling in RBC. Show more

Keywords: Remote ischemia preconditioning, red blood cell-nitric oxide synthase, deformability, nitric oxide

DOI: 10.3233/CH-152039

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 185-197, 2016

Authors: Grau, Marijke | Lauten, Alexander | Hoeppener, Steffen | Goebel, Bjoern | Brenig, Julian | Jung, Christian | Bloch, Wilhelm | Suhr, Frank

Article Type: Research Article

Abstract: The aim was to study impacts of mild to severe hypoxia on human red blood cell (RBC)-nitric oxide synthase (NOS)-dependent NO production, protein S-nitrosylation and deformability. Ambient air oxygen concentration of 12 healthy subjects was step-wisely reduced from 20.95% to 16.21%, 12.35%, 10% and back to 20.95%. Additional in vitro experiments involved purging of blood (±sodium nitrite) with gas mixtures corresponding to in vivo intervention. Vital and hypoxia-associated parameters showed physiological adaptation to changing demands. Activation of RBC-NOS decreased with increasing hypoxia. RBC deformability, which is influenced by RBC-NOS activation, decreased under mild hypoxia, but surprisingly …increased at severe hypoxia in vivo and in vitro . This was causatively induced by nitrite reduction to NO which increased S-nitrosylation of RBC α - and β -spectrins –a critical step to improve RBC deformability. The addition of sodium nitrite prevented decreases of RBC deformability under hypoxia by sustaining S-nitrosylation of spectrins suggesting compensatory mechanisms of non-RBC-NOS-produced NO. The results first time indicate a direct link between maintenance of RBC deformability under severe hypoxia by non-enzymatic NO production because RBC-NOS activation is reduced. These data improve our understanding of physiological mechanisms supporting adequate blood and, thus, oxygen supply to different tissues under severe hypoxia. Show more

Keywords: Humans, nitric oxide, normobaric hypoxia, red blood cells, red blood cell deformability, red blood cell-nitric oxide synthase

DOI: 10.3233/CH-162044

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 199-215, 2016

Authors: Jancsó, G. | Arató, E. | Hardi, P. | Nagy, T. | Pintér, Ö. | Fazekas, G. | Gasz, B. | Takacs, I. | Menyhei, G. | Kollar, L. | Sínay, L.

Article Type: Research Article

Abstract: Revascularization after long term aortic ischaemia in vascular surgery induces reperfusion injury accompanied with oxidative stress and inflammatory responses. The hypothesis of this study was that the aortic occlusion followed by controlled reperfusion (CR) can reduce the ischaemia-reperfusion injury, the systemic and local inflammatory response induced by oxidative stress. Animal model was used. Control group: animals underwent a 4-hour infrarenal aortic occlusion followed by continuous reperfusion. Treated group: animals were treated with CR: after a 4-hour infrarenal aortic occlusion we made CR for 30 minutes with the crystalloid reperfusion solution (blood: crystalloid solution ratio 1:1) on pressure 60 Hgmm. Blood …samples were collected different times. The developing oxidative stress was detected by the plasma levels of malondialdehyde, reduced glutathion, thiol groups and superoxide dismutase. The inflammatory response was measured by phorbol myristate acetate-induced leukocyte reactive oxygen species production and detection of change in myeloperoxidase levels. The animals were anaesthetized one week after terminating ligation and biopsy was taken from quadriceps muscle and large parenchymal organs. CR significantly reduced the postischaemic oxydative stress and inflammatory responses in early reperfusion period. Pathophysiological results: The rate of affected muscle fibers by degeneration was significantly higher in the untreated animal group. The infiltration of leukocytes in muscle and parenchymal tissues was significantly lower in the treatedgroup. CR can improve outcome after acute lower-limb ischaemia. The results confirm that CR might be also a potential therapeutic approach in vascular surgery against reperfusion injury in acute limb ischaemia. Supported by OTKA K108596. Show more

Keywords: Controlled reperfusion, reperfusion injury, aortic ischaemia

DOI: 10.3233/CH-152038

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 217-234, 2016

Authors: Kenyeres, P. | Sinay, L. | Jancso, G. | Rabai, M. | Toth, A. | Toth, K. | Arato, E.

Article Type: Research Article

Abstract: INTRODUCTION: Restoration of blood flow after prolonged acute ischemia causes further injury to tissues. The role of increased oxidative stress is emphasized in the pathogenesis, and impairment of hemorheological factors may also hinder proper microcirculation. Controlled reperfusion at lowered pressure with diluted blood may help to decrease reperfusion injury. METHODS: Four-hour infrarenal aortic clamping was performed in 16 Yorkshire pigs. In 8 animals blood flow was restored subsequently (full reperfusion, FR), in the other 8 animals clamping was followed by an initial 30 minutes of controlled reperfusion (CR) at 60 mmHg pressure with a 1 : 1 ratio mixture of …blood and reperfusion solution. Blood samples were taken before the intervention, at the end of ischemia, 15 minutes, 60 minutes, 1 day and 1 week after the start of reperfusion. Hemorheological parameters were measured. RESULTS: Hematocrit, plasma and whole blood viscosity decreased significantly during CR, these attenuated at 1 day. At 1 week whole blood and plasma viscosities were elevated in the FR group. Erythrocyte deformability did not change significantly at any measurements. Erythrocyte aggregation decreased during CR but not in FR, and was found elevated in both groups at 1 week. CONCLUSION: Our results suggest slightly improved hemorheological properties in case of controlled reperfusion compared to full reperfusion, which may help to reduce tissue damage. Show more

Keywords: Reperfusion injury, controlled reperfusion, hemorheological parameters

DOI: 10.3233/CH-162059

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 235-243, 2016

Authors: Kang, Jing | Li, Yuanyuan | Hu, Ke | Lu, Wen | Zhou, Xiufang | Yu, Shuhui | Xu, Lifang

Article Type: Research Article

Abstract: Although both chronic intermittent hypoxia (CIH) and chronic continuous hypoxia (CCH) have effects on hemorheology, we do not know whether their roles are the same. In this study, we explored the effect of simulated-apnea CIH on hemorheology in experimental rats and compared with the effect of CCH. 45 adult SD rats were randomly divided into the normoxic control group, CCH and CIH groups. CIH rats were given nitrogen and air alternately for 8 hours per day and the experiment lasted for 5 weeks. The control group were placed in the normoxia animal chambers, and the CCH rats were housed in …the same chambers which were continuously given normobaric hypoxia (FiO2  = 10%). After the preparations, the blood samples were taken and the hemorheology were determined. Compared with control group, the whole blood apparent viscosity, plasma viscosity, hematocrit, erythrocyte aggregation index and electrophoresis index, platelet aggregation rate and fibrinogen significantly increased in CIH group and CCH group. The whole blood viscosity, plasma viscosity, hematocrit and fibrinogen values were much higher in CCH group than in CIH group. However, there was not significantly difference in RBC deformation index or rigidity index among the three groups and no significantly differences were found in the effects on RBC rheological property between CIH and CCH. Our results suggest that intermittent hypoxia and continuous hypoxia increase whole blood viscosity, impair the functions of red blood cells and promote the platelet aggregation in model rats. Moreover, CCH had a greater effect on blood rheology than CIH. Show more

Keywords: Chronic intermittent hypoxia, continuous hypoxia, hemorheology, rat

DOI: 10.3233/CH-151973

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 245-255, 2016

Authors: Rohm, Ilonka | Aderhold, Nicole | Ratka, Josephine | Goebel, Bjoern | Franz, Marcus | Pistulli, Rudin | Gecks, Thomas | Figulla, Hans Reiner | Yilmaz, Atilla | Jung, Christian

Article Type: Research Article

Abstract: INTRODUCTION: Hypoxia is known to affect the immune system. It leads to an increase in pro-inflammatory cytokines such as interleukin-6 and influences the number of different inflammatory cells. This study investigates the effect of hypoxia on the number of different subsets of circulating human dendritic cells (DCs) as professional antigen-presenting cells. METHODS: The number of circulating DCs was determined via Fluorescence activated cell sorting analysis in peripheral blood of 17 healthy volunteers (age 35.9±2.6 years) in normoxia (baseline, BL), hypoxia (altitude 3000 m, alpine passive escalation), and again normoxia (follow-up, FU). RESULTS: Exposure to hypobaric hypoxia …in high altitude, 3000 m, led to a significant decrease in the participants’ oxygen saturation, and an increase in the breathing frequency whereas blood pressure and heart rate were not significantly altered. FACS analysis revealed a significant hypoxia induced decrease in circulating plasmacytoid (p) DCs compared to baseline levels (BL: 0.10 [0.08–0.18] % of white blood cell count (WBC), 3000 m: 0.03 [0.02–0.06] % WBC, p  < 0.001). During follow up, again a significant reconstitution of circulating pDCs was observed (FU: 0.16±[0.11–0.26] % WBC, p  = 0.0013). CONCLUSION: Hypobaric hypoxia caused by exposure to altitude results in a significant reduction in the number of circulating pDCs. Show more

Keywords: Dendritic cells, inflammation, hypobaric hypoxia, altitude

DOI: 10.3233/CH-152035

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 257-265, 2016

Authors: An, Xin | Zhang, Heng | Sun, Yini | Ma, Xiaochun

Article Type: Research Article

Abstract: OBJECT: This study aimed at exploring what level of the microcirculation alteration could weaken the decrease of ScvO2 (or the increase of O2 ER) and further result in an abnormally elevated ScvO2 . METHODS: Beagles were randomly assigned into control (n  = 5) and shock group (n  = 5). The canines in shock group were intravenously injected with live E. coli (3.5×108 cfu/kg), and the ones in control group were injected with sterile saline. The experiment continued to the animals’ death or for a maximum of 24 hours. Hemodynamic parameters, blood gas and inflammatory cytokines level were collected. …Microcirculatory parameters were assessed with Sidestream Dark Field (SDF) imaging. The correlation between the microcirculation and oxygen metabolism or inflammatory cytokine, meanwhile the correlation between the oxygen metabolism and inflammatory cytokine was assessed. RESULTS: E. coli infusion induced hypodynamic shock. The correlation between microcirculation and oxygen metabolism or inflammatory cytokine, and The correlation between the oxygen metabolism and inflammatory cytokine (O2 ER vs. MFI: r  = –0.700, P  < 0.01; O2 ER vs. PVD: r  = –0.677, P  < 0.01; O2 ER vs. PPV: r  = –0.538, P  < 0.01; MFI vs. IL-6: r  = –0.780, P  < 0.01; PPV vs. IL-6: r  = –0.621, P  < 0.01; MFI vs. TNF-α : r  = –0.636, P  < 0.01; PPV vs. TNF-α : r  = –0.561, P  < 0.01) were observed. CONCLUSIONS: The increase of O2 ER cannot be weakened by the microcirculatory failure. Show more

Keywords: Oxygen consumption rate, microcirculation, septic shock, inflammatory cytokines, canine

DOI: 10.3233/CH-152022

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 267-279, 2016

Authors: Neumann, Thomas | Baertschi, Michael | Vilser, Walthard | Drinda, Stefan | Franz, Marcus | Brückmann, Andreas | Wolf, Gunter | Jung, Christian

Article Type: Research Article

Abstract: PURPOSE: To measure static and dynamic changes of retinal vessels in response to normobaric hypoxia (NH, study A) and hypobaric hypoxia (HH, study B). METHODS: Study A included 10 healthy individuals exposed to a simulated altitude of 5500 meters in a NH chamber; study B included 17 individuals studied after ascent to 3000-meter altitude. Retinal vessel diameter, response to flicker light, retinal oxygen saturation and retinal venous pressure were measured at baseline, under the corresponding hypoxia condition. The effects of macitentan, an endothelin receptor antagonist, were examined in study B. RESULTS: The mean age of …participants was 34.6±9.3 years in study A and 36.7±10.8 years in study B. Retinal arterial and venous diameter increased, arterial and venous response to flicker light decreased, while retinal oxygen saturation remained stable under both experimental conditions. Retinal venous pressure increased in six individuals after ascent to 3000 meters and normalized after macitentan treatment. The occurrence of acute mountain sickness (AMS) correlated only with the decrease of arterial constriction after ascent to 3000 meters. CONCLUSIONS: Retinal arterial and venous vessels react to NH and HH with a diameter increase and an impaired response to flicker light. Macitentan was capable to normalize the increased retinal venous pressure observed at high altitudes. Show more

Keywords: Digital vessel analysis, retinal, hypoxia, high altitude, macitentan, retinal venous pressure

DOI: 10.3233/CH-162041

Citation: Clinical Hemorheology and Microcirculation, vol. 63, no. 3, pp. 281-292, 2016