Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model

1998 ◽  
Vol 275 (6) ◽  
pp. H2170-H2180 ◽  
Author(s):  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
Michael McCarthy ◽  
Hiromi Sakai ◽  
Marcos Intaglietta
Keyword(s):  
Molecular Weight ◽  
Shear Stress ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Capillary Perfusion ◽  
Low Viscosity ◽  
Arterial Blood ◽  
Wall Shear ◽  
Stress Dependent

Effect of increasing blood viscosity during extreme hemodilution on capillary perfusion and tissue oxygenation was investigated in the awake hamster skinfold model. Two isovolemic hemodilution steps were performed with 6% Dextran 70 [molecular weight (MW) = 70,000] until systemic hematocrit (Hct) was reduced by 65%. A third step reduced Hct by 75% and was performed with the same solution [low viscosity (LV)] or a high-molecular-weight 6% Dextran 500 solution [MW = 500,000, high viscosity (HV)]. Final plasma viscosities were 1.4 and 2.2 cP (baseline of 1.2 cP). Hct was reduced to 11.2 ± 1.1% from 46.2 ± 1.5% for LV and to 11.9 ± 0.7% from 47.3 ± 2.1% for HV. HV produced a greater mean arterial blood pressure than LV. Functional capillary density (FCD) was substantially higher after HV (85 ± 12%) vs. LV (38 ± 30%) vs. baseline (100%).[Formula: see text] levels measured with Pd-porphyrin phosphorescence microscopy were not statistically changed from baseline until after the third hemodilution step. Wall shear rate (WSR) decreased in arterioles and venules after LV and only in arterioles after HV. Wall shear stress (WSR × plasma viscosity) was substantially higher after HV vs. LV. Increased mean arterial pressure and shear stress-dependent release of endothelium-derived relaxing factor are possible mechanisms that improved arteriolar and venular blood flow and FCD after HV vs. LV exchange protocols.

Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion

2005 ◽  
Vol 288 (4) ◽  
pp. H1730-H1739 ◽  
Author(s):  
Amy G. Tsai ◽  
Cesar Acero ◽  
Patricia R. Nance ◽  
Pedro Cabrales ◽  
John A. Frangos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Capillary Density ◽  
Blood Stream ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Low Viscosity ◽  
Enhanced Production ◽  
Dextran 70 ◽  
Nitric Oxide Concentration

We tested the hypothesis that high-viscosity (HV) plasma in extreme hemodilution causes wall shear stress to be greater than low-viscosity (LV) plasma, leading to enhanced production of nitric oxide (NO). The perivascular concentration of NO was measured in arterioles and venules and the tissue of the hamster chamber window model, subjected to acute extreme hemodilution, with a hematocrit (Hct) of 11% using Dextran 500 ( n = 6) or Dextran 70 ( n = 5) with final plasma viscosities of 1.99 ± 0.11 and 1.33 ± 0.04 cp, respectively. HV plasma significantly increased the periarteriolar, perivenular, and tissue NO concentration by 2.0, 1.9, and 1.4 times the control ( n = 7). The NO concentration with LV plasma was not statistically different from control. Arteriolar shear stress was significantly increased in HV plasma relative to LV plasma in arterioles but not in venules. Aortic endothelial NO synthase (eNOS) protein expression was increased with HV plasma but not with LV plasma. There was a weak correlation between perivascular NO concentration and the locally calculated shear stress induced by the procedures, when blood viscosity was corrected according to Hct values previously determined in studies of microvascular Hct distribution. The finding that the periarteriolar and venular NO concentration in HV plasma was the same although arteriolar shear stress was significantly greater than venular shear stress maybe be due to differences in vessel wall metabolism between arterioles and venules and the presence of NO transport through the blood stream in the microcirculation. Results support the concept that in extreme hemodilution HV plasma maintains functional capillary density through a NO-mediated vasodilatation.

Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions

2006 ◽  
Vol 291 (5) ◽  
pp. H2445-H2452 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai
Keyword(s):  
Flow Distribution ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Arterial Blood ◽  
Chamber Model ◽  
Kidney Liver ◽  
Window Chamber

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% ( level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.

scholarly journals Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins

2010 ◽  
Vol 298 (3) ◽  
pp. H1062-H1071 ◽  
Author(s):  
Pedro Cabrales ◽  
Yipin Zhou ◽  
David R. Harris ◽  
Andre F. Palmer
Keyword(s):  
Molecular Weight ◽  
Exchange Transfusion ◽  
Tissue Oxygenation ◽  
Capillary Density ◽  
High Viscosity ◽  
Therapeutic Agents ◽  
Mechanical Stimuli ◽  
Capillary Perfusion ◽  
Ultrahigh Molecular Weight ◽  
T State

Hemoglobin (Hb)-based O2 carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O2 deficit under conditions of anemia and traumatic blood loss. The O2 transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O2 delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). After an initial moderate hemodilution to 18% hematocrit, animals were randomly assigned to exchange transfusion groups based on the type of PolybHb solution used (namely, T-state PolybHb and R-state PolybHb groups). Measurements of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O2 levels were performed at 11% hematocrit. Both PolybHbs were infused at 10 g/dl, and their viscosities were higher than nondiluted blood. Restitution of the O2 carrying capacity with T-state PolybHb exhibited lower arterial pressure and higher functional capillary density compared with R-state PolybHb. Central arterial O2 tensions increased significantly for R-state PolybHb compared with T-state PolybHb; conversely, microvascular O2 tensions were higher for T-state PolybHb compared with R-state PolybHb. The increased tissue Po2 attained with T-state PolybHb results from the larger amount of O2 released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O2 affinity of R-state PolybHb prevented O2 bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O2 carrier, is a quintessential example of an appropriately engineered O2 carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs.

Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity

2006 ◽  
Vol 291 (2) ◽  
pp. H581-H590 ◽  
Author(s):  
Pedro Cabrales ◽  
Judith Martini ◽  
Marcos Intaglietta ◽  
Amy G. Tsai
Keyword(s):  
Shear Stress ◽  
Oxygen Content ◽  
Blood Viscosity ◽  
Capillary Density ◽  
Noninvasive Methods ◽  
Low Viscosity ◽  
Wall Shear ◽  
Oxygen Carrying Capacity ◽  
Level 2

Responses to exchange transfusion with red blood cells (RBCs) containing methemoglobin (MetRBC) were studied in an acute isovolemic hemodiluted hamster window chamber model to determine whether oxygen content participates in the regulation of systemic and microvascular conditions during extreme hemodilution. Two isovolemic hemodilution steps were performed with 6% dextran 70 kDa (Dex70) until systemic hematocrit (Hct) was reduced to 18% ( Level 2). A third-step hemodilution reduced the functional Hct to 75% of baseline by using either a plasma expander (Dex70) or blood adjusted to 18% Hct with all MetRBCs. In vivo functional capillary density (FCD), microvascular perfusion, and oxygen distribution in microvascular networks were measured by noninvasive methods. Methylene blue was administered intravenously to reduce methemoglobin (rRBC), which increased oxygen content with no change in Hct or viscosity from MetRBC. Final blood viscosities after the entire protocol were 2.1 cP for Dex70 and 2.8 cP for MetRBC (baseline, 4.2 cP). MetRBC had a greater mean arterial pressure (MAP) than did Dex70. FCD was substantially higher for MetRBC [82 (SD 6) of baseline] versus Dex70 [38 (SD 10) of baseline], and reduction of methemoglobin to oxyhemoglobin did not change FCD [84% (SD 5) of baseline]. Po2 levels measured with palladium-meso-tetra(4-carboxyphenyl)porphyrin phosphorescence were significantly changed for Dex70 and MetRBC compared with Level 2 (Hct 18%). Reduction of methemoglobin to oxyhemoglobin partially restored Po2 to Level 2. Wall shear rate and wall shear stress decreased in arterioles and venules for Dex70 and did not change for MetRBC or rRBC. Increased MAP and shear stress-mediated factors could be the possible mechanisms that improved perfusion flow and FCD after exchange for MetRBC. Thus the fall in systemic and microvascular conditions during extreme hemodilution with low-viscosity plasma expanders seems to be, in part, from the decrease in blood viscosity independent of the reduction in oxygen content.

Endothelial NOS is main mediator for shear stress-dependent angiogenesis in skeletal muscle after prazosin administration

2004 ◽  
Vol 287 (5) ◽  
pp. H2300-H2308 ◽  
Author(s):  
Oliver Baum ◽  
Luis Da Silva-Azevedo ◽  
Gregor Willerding ◽  
Achim Wöckel ◽  
Gerit Planitzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Knockout Mice ◽  
Skeletal Muscles ◽  
Capillary Density ◽  
Enos Expression ◽  
Wall Shear ◽  
Stress Dependent ◽  
Endothelial Nitric Oxide

The increase of wall shear stress in capillaries by oral administration of the α1-adrenergic receptor antagonist prazosin induces angiogenesis in skeletal muscles. Because endothelial nitric oxide synthase (eNOS) is upregulated in response to elevated wall shear stress, we investigated the relevance of eNOS for prazosin-induced angiogenesis in skeletal muscles. Prazosin and/or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) were given to C57BL/6 wild-type mice and eNOS-knockout mice for 14 days. The capillary-to-fiber (C/F) ratio and capillary density (CD; no. of capillaries/mm2) were determined in frozen sections from extensor digitorum longus (EDL) muscles of these mice. Immunoblotting was performed to quantify eNOS expression in endothelial cells isolated from skeletal muscles, whereas VEGF (after precipitation with heparin-agarose) and neuronal NOS (nNOS) concentrations were determined in EDL solubilizates. In EDL muscles of C57BL/6 mice treated for 14 days, the C/F ratio was 28% higher after prazosin administration and 11% higher after prazosin and l-NAME feeding, whereas the CD increased by 21 and 13%, respectively. The C/F ratio was highest after day 4 of prazosin treatment and decreased gradually to almost constant values after day 8. Prazosin administration led to elevation of eNOS expression. VEGF levels were lowest at day 4, whereas nNOS values decreased after day 8. In EDL muscles of eNOS-knockout mice, no significant changes in C/F ratio, CD, or VEGF and nNOS expression were observed in response to prazosin administration. Our data suggest that the presence of eNOS is essential for prazosin-induced angiogenesis in skeletal muscle, albeit other signaling molecules might partially compensate for or contribute to this angiogenic activity. Furthermore, subsequent remodeling of the capillary system accompanied by sequential downregulation of VEGF and nNOS in skeletal muscle fibers characterizes shear stress-dependent angiogenesis.

Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution

2005 ◽  
Vol 288 (4) ◽  
pp. H1708-H1716 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai ◽  
Marcos Intaglietta
Keyword(s):  
Oxygen Consumption ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
The Other ◽  
Plasma Expander ◽  
Low Viscosity ◽  
Microvascular Changes ◽  
Dextran 70 ◽  
Window Chamber

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution ( n = 6 each group). Final plasma viscosities were 1.4 ± 0.2, 2.2 ± 0.1, and 2.7 ± 0.2 cp, respectively, ( P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 ± 0.2, 2.9 ± 0.4, and 3.9 ± 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 ± 16%, whereas the two high-viscosity solutions were 71 ± 15% and 76 ± 12% ( P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po2 was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po2 showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline ( P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher ( P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.

Dexmedetomidine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis

2015 ◽  
Vol 122 (3) ◽  
pp. 619-630 ◽  
Author(s):  
Marcos L. Miranda ◽  
Michelle M. Balarini ◽  
Eliete Bouskela
Keyword(s):  
Blood Gases ◽  
Capillary Density ◽  
Sepsis Syndrome ◽  
In Vivo Studies ◽  
Experimental Sepsis ◽  
Leukocyte Rolling ◽  
Capillary Perfusion ◽  
Arterial Blood ◽  
Baseline Values

Abstract Background: Dexmedetomidine, an α-2 adrenergic receptor agonist, has already been used in septic patients although few studies have examined its effects on microcirculatory dysfunction, which may play an important role in perpetuating sepsis syndrome. Therefore, the authors have designed a controlled experimental study to characterize the microcirculatory effects of dexmedetomidine in an endotoxemia rodent model that allows in vivo studies of microcirculation. Methods: After skinfold chamber implantation, 49 golden Syrian hamsters were randomly allocated in five groups: (1) control animals; (2) nonendotoxemic animals treated with saline; (3) nonendotoxemic animals treated with dexmedetomidine (5.0 μg kg−1 h−1); (4) endotoxemic (lipopolysaccharide 1.0 mg/kg) animals treated with saline; and (5) endotoxemic animals treated with dexmedetomidine. Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables and venular leukocyte rolling and adhesion. Mean arterial blood pressure, heart rate, arterial blood gases, and lactate concentrations were also documented. Results: Lipopolysaccharide administration increased leukocyte rolling and adhesion and decreased capillary perfusion. Dexmedetomidine significantly attenuated these responses: compared with endotoxemic animals treated with saline, those treated with dexmedetomidine had less leukocyte rolling (11.8 ± 7.2% vs. 24.3 ± 15.0%; P &lt; 0.05) and adhesion (237 ± 185 vs. 510 ± 363; P &lt; 0.05) and greater functional capillary density (57.4 ± 11.2% of baseline values vs. 45.9 ± 11.2%; P &lt; 0.05) and erythrocyte velocity (68.7 ± 17.6% of baseline values vs. 54.4 ± 14.8%; P &lt; 0.05) at the end of the experiment. Conclusions: Dexmedetomidine decreased lipopolysaccharide-induced leukocyte–endothelial interactions in the hamster skinfold chamber microcirculation. This was accompanied by a significant attenuation of capillary perfusion deficits, suggesting that dexmedetomidine yields beneficial effects on endotoxemic animals’ microcirculation.

scholarly journals Branching exponent heterogeneity and wall shear stress distribution in vascular trees

2001 ◽  
Vol 280 (3) ◽  
pp. H1256-H1263 ◽  
Author(s):  
Kelly L. Karau ◽  
Gary S. Krenz ◽  
Christopher A. Dawson
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Coefficient Of Variation ◽  
Vessel Diameter ◽  
Mean Value ◽  
Heterogeneous Distribution ◽  
Uniform Shear ◽  
The Mean ◽  
Wall Shear ◽  
Stress Dependent

A bifurcating arterial system with Poiseuille flow can function at minimum cost and with uniform wall shear stress if the branching exponent ( z) = 3 [where z is defined by ( D 1) z = ( D 2) z + ( D 3) z ; D 1 is the parent vessel diameter and D 2 and D 3 are the two daughter vessel diameters at a bifurcation]. Because wall shear stress is a physiologically transducible force, shear stress-dependent control over vessel diameter would appear to provide a means for preserving this optimal structure through maintenance of uniform shear stress. A mean z of 3 has been considered confirmation of such a control mechanism. The objective of the present study was to evaluate the consequences of a heterogeneous distribution of z values about the mean with regard to this uniform shear stress hypothesis. Simulations were carried out on model structures otherwise conforming to the criteria consistent with uniform shear stress when z = 3 but with varying distributions of z. The result was that when there was significant heterogeneity in z approaching that found in a real arterial tree, the coefficient of variation in shear stress was comparable to the coefficient of variation in z and nearly independent of the mean value of z. A systematic increase in mean shear stress with decreasing vessel diameter was one component of the variation in shear stress even when the mean z = 3. The conclusion is that the influence of shear stress in determining vessel diameters is not, per se, manifested in a mean value of z. In a vascular tree having a heterogeneous distribution in zvalues, a particular mean value of z (e.g., z = 3) apparently has little bearing on the uniform shear stress hypothesis.

Patient-specific three-dimensional simulation of LDL accumulation in a human left coronary artery in its healthy and atherosclerotic states

2009 ◽  
Vol 296 (6) ◽  
pp. H1969-H1982 ◽  
Author(s):  
Ufuk Olgac ◽  
Dimos Poulikakos ◽  
Stefan C. Saur ◽  
Hatem Alkadhi ◽  
Vartan Kurtcuoglu
Keyword(s):  
Shear Stress ◽  
Coronary Artery ◽  
Left Coronary Artery ◽  
Three Dimensional ◽  
Arterial Blood Flow ◽  
Patient Specific ◽  
Computed Tomography Images ◽  
Arterial Blood ◽  
Diseased State ◽  
Stress Dependent

We calculate low-density lipoprotein (LDL) transport from blood into arterial walls in a three-dimensional, patient-specific model of a human left coronary artery. The in vivo anatomy data are obtained from computed tomography images of a patient with coronary artery disease. Models of the artery anatomy in its healthy and diseased states are derived after segmentation of the vessel lumen, with and without the detected plaque, respectively. Spatial shear stress distribution at the endothelium is determined through the reconstruction of the arterial blood flow field using computational fluid dynamics. The arterial endothelium is represented by a shear stress-dependent, three-pore model, taking into account blood plasma and LDL passage through normal junctions, leaky junctions, and the vesicular pathway. Intraluminal pressures of 70 and 120 mmHg are employed as the normal and hypertensive operating pressures, respectively. By applying our model to both the healthy and diseased states, we show that the location of the plaque in the diseased state corresponds to one of the two sites with predicted high-LDL concentration in the healthy state. We further show that, in the diseased state, the site with high-LDL concentration has shifted distal to the plaque, which is in agreement with the clinical observation that plaques generally grow in the downstream direction. We also demonstrate that hypertension leads to increased number of regions with high-LDL concentration, elucidating one of the ways in which hypertension may promote atherosclerosis.

scholarly journals Kappa-Carrageenan-Based Dual Crosslinkable Bioink for Extrusion Type Bioprinting

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2377
Author(s):  
Wonseop Lim ◽  
Gyeong Jin Kim ◽  
Hyun Woo Kim ◽  
Jiyeon Lee ◽  
Xiaowei Zhang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Physical Properties ◽  
New Technology ◽  
High Viscosity ◽  
3D Bioprinting ◽  
Cell Compatibility ◽  
Low Viscosity ◽  
Shape Retention ◽  
Kappa Carrageenan ◽  
Nih 3T3

Bioink based 3D bioprinting is a promising new technology that enables fabrication of complex tissue structures with living cells. The printability of the bioink depends on the physical properties such as viscosity. However, the high viscosity bioink puts shear stress on the cells and low viscosity bioink cannot maintain complex tissue structure firmly after the printing. In this work, we applied dual crosslinkable bioink using Kappa-carrageenan (κ-CA) to overcome existing shortcomings. κ-CA has properties such as biocompatibility, biodegradability, shear-thinning and ionic gelation but the difficulty of controlling gelation properties makes it unsuitable for application in 3D bioprinting. This problem was solved by synthesizing methacrylated Kappa-carrageenan (MA-κ-CA), which can be dual crosslinked through ionic and UV (Ultraviolet) crosslinking to form hydrogel using NIH-3T3 cells. Through MA substitutions, the rheological properties of the gel could be controlled to reduce the shear stress. Moreover, bioprinting using the cell-laden MA-κ-CA showed cell compatibility with enhanced shape retention capability. The potential to control the physical properties through dual crosslinking of MA-κ-CA hydrogel is expected to be widely applied in 3D bioprinting applications.

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