Regional transcapillary albumin exchange in rodent endotoxaemia: effects of fluid resuscitation and inhibition of nitric oxide synthase

Sepsis is characterized by increased microvascular permeability and regional variations in capillary perfusion, which may be modulated by nitric oxide (NO) and reversed by fluid resuscitation (FR). The effects of saline FR and NO synthase blockade [by NG-nitro-L-arginine methyl ester (L-NAME)] on microvascular albumin transport and perfused capillary density were assessed in anaesthetized Wistar rats with acute normodynamic endotoxaemia. Separate dual-isotope techniques were employed to measure the permeability index (PIA) and the permeability×surface area product index (PIB), which provide different and complementary information regarding blood–tissue albumin exchange. PIA represents the tissue/blood distribution volume ratio of albumin. PIB is a composite measure of endothelial permeability and the vascular surface area available for albumin exchange, and therefore takes into account the effect of altered blood volume. Capillary density was quantified by fluorescence microscopy following circulation of Evans Blue-labelled albumin. Compared with controls, PIA was reduced significantly in lipopolysaccharide (LPS)-treated animals in skeletal muscle and skin, probably due to blood volume redistribution rather than to changes in permeability. PIB was increased significantly in LPS-treated animals in the kidney, mesentery, skeletal muscle, skin and lung, and in the small bowel following FR. FR also improved the LPS-induced metabolic base deficit, but did not alter capillary density. L-NAME significantly attenuated the LPS-induced rise in PIB in the lung. In conclusion, acute endotoxaemia induces tissue-dependent variations in microvascular albumin exchange. FR improves acid–base disturbance in endotoxaemia, through mechanisms other than microvascular recruitment. NO appears to increase microvascular permeability in endotoxaemia, an effect that may be attenuated by L-NAME, particularly in the lung.

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Microvascular pressure, surface area, and permeability in isolated hindquarters of SHR

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1985.249.3.h498 ◽

1985 ◽

Vol 249 (3) ◽

pp. H498-H504

Author(s):

R. J. Korthuis ◽

C. R. Kerr ◽

M. I. Townsley ◽

A. E. Taylor

Keyword(s):

Skeletal Muscle ◽

Capillary Pressure ◽

Surface Area ◽

Convective Transport ◽

Microvascular Permeability ◽

Spontaneously Hypertensive ◽

Pressure Surface ◽

Total Plasma Protein ◽

Wistar Kyoto ◽

Osmotic Reflection Coefficient

The transvascular escape rate (TER) of labeled albumin is reported to increase in essential hypertension. However, the mechanism for this augmented rate of protein efflux is uncertain and may be related to increased microvascular permeability, surface area, and/or pressure. To determine the possible contributions of these mechanisms to increased TER of protein, the osmotic reflection coefficient for total plasma protein, capillary filtration coefficient, and effective capillary pressure were estimated in isolated hindquarters of age-matched (12-13 wk) spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar (WR) rats. Estimates of the reflection and filtration coefficients were not significantly different in SHR, WKY, and WR. However, capillary pressure was significantly greater in SHR than in normotensive controls. These results indicate that 1) skeletal muscle microvascular permeability and surface area are similar in SHR, WKY, and WR; 2) effective capillary pressure is greater in SHR than WKY or WR; and 3) if TER for protein is elevated in hypertensive skeletal muscle, the primary mechanism for this process may be increased convective transport of protein secondary to elevated microvascular hydrostatic pressure.

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Sizes of components in frog skeletal muscle measured by methods of stereology.

The Journal of General Physiology ◽

10.1085/jgp.66.1.31 ◽

1975 ◽

Vol 66 (1) ◽

pp. 31-45 ◽

Cited By ~ 154

Author(s):

B A Mobley ◽

B R Eisenberg

Keyword(s):

Skeletal Muscle ◽

Sarcoplasmic Reticulum ◽

Surface Area ◽

Volume Ratio ◽

Sartorius Muscle ◽

Morphological Parameters ◽

Frog Skeletal Muscle ◽

Fiber Volume ◽

Transverse Tubules ◽

Terminal Cisternae

Stereological techniques of point and intersection counting were used to measure morphological parameters from light and electron micrographs of frog skeletal muscle. Results for sartorius muscle are as follows: myofibrils comprise 83% of fiber volume; their surface to volume ratio is 3.8 mum-1. Mitochondria comprise 1.6% of fiber volume. Transverse tubules comprise 0.32% of fiber volume, and their surface area per volume of fiber is 0.22 mum-1. Terminal cisternae of the sarcoplasmic reticulum comprise 4.1% of fiber volume; their surface area per volume of fiber is 0.54 mum-1. Longitudinal sarcoplasmic reticullum comprises 5.0% of fiber volume, and its surface area per volume of fiber is 1.48 mum-1. Longitudinal bridges between terminal cisternae on either side of a Z disk were observed infrequently; they make up only 0.035% of fiber volume and their surface area per volume of fiber is 0.009 mum-1. T-SR junction occurs over 67% of the surface of transverse tubules and over 27% of the surface of terminal cisternae. The surface to volume ratio of the caveolae is 48 mum-1; caveolae may increase the sarcolemmal surface area by 47%. Essentially the same results were obtained from semitendinosus fibers.

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Fluid resuscitation therapy in endotoxemic hamsters improves survival and attenuates capillary perfusion deficits and inflammatory responses by a mechanism related to nitric oxide

Journal of Translational Medicine ◽

10.1186/s12967-014-0232-z ◽

2014 ◽

Vol 12 (1) ◽

Cited By ~ 6

Author(s):

Nivaldo Ribeiro Villela ◽

Ana Olimpia Maia Teixeira dos Santos ◽

Marcos Lopes de Miranda ◽

Eliete Bouskela

Keyword(s):

Nitric Oxide ◽

Fluid Resuscitation ◽

Inflammatory Responses ◽

Capillary Perfusion ◽

Perfusion Deficits

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Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00390.2010 ◽

2012 ◽

Vol 302 (3) ◽

pp. H603-H610 ◽

Cited By ~ 7

Author(s):

F. Rezaeian ◽

R. Wettstein ◽

C. Scheuer ◽

K. Bäumker ◽

A. Bächle ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Nuclear Factor Κb ◽

Capillary Density ◽

Capillary Perfusion ◽

Ischemic Necrosis ◽

Dorsal Skinfold Chamber ◽

Tissue Protection ◽

Wound Breakdown ◽

Oxide Synthase

Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) Nω-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis ( P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia.

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Prevention of Platelet Adhesion and Aggregation by a Glutardialdehyde-Stabilized Heparin Surface

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649228 ◽

1977 ◽

Vol 37 (02) ◽

pp. 274-282 ◽

Cited By ~ 40

Author(s):

P Olsson ◽

H Lagergren ◽

R Larsson ◽

K Rådegran

Keyword(s):

Platelet Aggregation ◽

Surface Area ◽

Blood Volume ◽

Platelet Adhesion ◽

Volume Ratio ◽

Heparin Coating ◽

Platelet Adhesion And Aggregation ◽

The Difference ◽

Foreign Surface

SummaryA stable heparinized surface was prepared by sequential treatment of polyethylene with water solutions of hexadecylamine hydrochloride, heparin and glutardialdehyde. In order to explain the “non-thrombogenic” properties of this surface, it was evaluated with regard to prevention of platelet adhesion and aggregation.Human heparinized blood (2 and 10 IU/ml) with 51Cr-labelled autologous platelets was rotated for 60 minutes in untreated and heparin-treated circular tubings. The surface area/blood volume ratio was varied and an air-blood interface was present. In untreated tubings, platelet adhesion and aggregation increased in proportion to the size of the surface area/blood volume ratio, irrespective of the heparin concentrations of the blood. In the heparin-treated tubings, there was no measurable platelet adhesion to the surface and no platelet aggregation in the blood. The difference between the heparinized and the untreated surfaces with regard to platelet adhesion was discernible even after 10 minutes storage of stagnant blood.It is concluded that platelet adhesion and aggregation induced by exposure of blood to a foreign surface in an in vitro experimental model can be prevented by a stable heparin coating of the surface.

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Reduced uterine perfusion pressure decreases functional capillary density in skeletal muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00641.2015 ◽

2015 ◽

Vol 309 (12) ◽

pp. H2002-H2007 ◽

Cited By ~ 4

Author(s):

Graham M. Fraser ◽

Jude S. Morton ◽

Sydney M. Schmidt ◽

Stephane Bourque ◽

Sandra T. Davidge ◽

...

Keyword(s):

Skeletal Muscle ◽

Continuous Flow ◽

Perfusion Pressure ◽

Capillary Density ◽

Functional Capillary Density ◽

Stopped Flow ◽

Sprague Dawley ◽

Capillary Perfusion ◽

Pregnant State ◽

Uterine Perfusion

The purpose of this study was to examine the functional and structural capillary density in the reduced uterine perfusion pressure (RUPP) model, which when performed during pregnancy is an established animal model of preeclampsia. We hypothesized that the RUPP model would be associated with capillary rarefaction and impaired capillary perfusion, which would be more pronounced in the pregnant state. Female Sprague-Dawley rats ( n = 32) were randomized to nonpregnancy (Nonpregnant) or breeding (Pregnant) at 12 wk of age and again to RUPP or SHAM surgeries on gestational day (GD) 14 (or equivalent age in nonpregnant rats). On GD 20 (or equivalent), capillary structure and perfusion of the extensor digitorum longus were imaged using digital intravital video microscopy. Functional videos were analyzed by a blinded observer to measure capillary density, expressed as capillaries per millimeter intersecting three staggered reference lines (200 μm). Flow was scored as the percentage of capillaries having 1) continuous, 2) intermittent, or 3) stopped flow. Total capillary density was not different between groups. There was a main effect of RUPP surgery resulting in decreased continuous flow vessels ( P < 0.01) and increased stopped flow ( P < 0.01), which was driven by differences between pregnant animals (Continuous flow: pregnant SHAM 80.1 ± 7.8% vs. pregnant RUPP 67.8 ± 11.2%, P < 0.05) (Stopped flow: pregnant SHAM 8.7 ± 3.2% vs. pregnant RUPP 17.9 ± 5.7%, P < 0.01). Our results demonstrate that the RUPP surgery is associated with a decrease in functional capillary density in skeletal muscle that is more pronounced in the pregnant state, which may contribute to the vascular pathophysiology observed in preeclampsia.

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Vasomotion in critically perfused muscle protects adjacent tissues from capillary perfusion failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.2.h550 ◽

2000 ◽

Vol 279 (2) ◽

pp. H550-H558 ◽

Cited By ~ 35

Author(s):

M. Rücker ◽

O. Strobel ◽

B. Vollmar ◽

F. Roesken ◽

M. D. Menger

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Capillary Flow ◽

Capillary Density ◽

Functional Capillary Density ◽

Sprague Dawley ◽

Capillary Perfusion ◽

Peripheral Tissues ◽

Flow Motion ◽

Stepwise Reduction

We analyzed the incidence and interaction of arteriolar vasomotion and capillary flow motion during critical perfusion conditions in neighboring peripheral tissues using intravital fluorescence microscopy. The gracilis and semitendinosus muscles and adjacent periosteum, subcutis, and skin of the left hindlimb of Sprague-Dawley rats were isolated at the femoral vessels. Critical perfusion conditions, achieved by stepwise reduction of femoral artery blood flow, induced capillary flow motion in muscle, but not in the periosteum, subcutis, and skin. Strikingly, blood flow within individual capillaries was decreased ( P < 0.05) in muscle but was not affected in the periosteum, subcutis, and skin. However, despite the flow motion-induced reduction of muscle capillary blood flow during the critical perfusion conditions, functional capillary density remained preserved in all tissues analyzed, including the skeletal muscle. Abrogation of vasomotion in the muscle arterioles by the calcium channel blocker felodipine resulted in a redistribution of blood flow within individual capillaries from cutaneous, subcutaneous, and periosteal tissues toward skeletal muscle. As a consequence, shutdown of perfusion of individual capillaries was observed that resulted in a significant reduction ( P < 0.05) of capillary density not only in the neighboring tissues but also in the muscle itself. We conclude that during critical perfusion conditions, vasomotion and flow motion in skeletal muscle preserve nutritive perfusion (functional capillary density) not only in the muscle itself but also in the neighboring tissues, which are not capable of developing this protective regulatory mechanism by themselves.

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