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

2000 ◽  
Vol 279 (2) ◽  
pp. H550-H558 ◽  
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.

scholarly journals Reduced uterine perfusion pressure decreases functional capillary density in skeletal muscle

2015 ◽  
Vol 309 (12) ◽  
pp. H2002-H2007 ◽  
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.

Insulin-mediated changes in leg blood flow are coupled to capillary density in skeletal muscle in healthy 70-year-old men

Metabolism ◽  
2001 ◽  
Vol 50 (9) ◽  
pp. 1078-1082 ◽  
Author(s):  
Anu Hedman ◽  
Per-Erik Andersson ◽  
Richard Reneland ◽  
Hans O. Lithell
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Capillary Density ◽  
Leg Blood Flow ◽  
Old Men

Periodic hemodynamics in skeletal muscle during local arterial pressure reduction

1992 ◽  
Vol 73 (3) ◽  
pp. 1077-1083 ◽  
Author(s):  
J. A. Schmidt ◽  
M. Intaglietta ◽  
P. Borgstrom
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Slow Wave ◽  
Control Period ◽  
Wave Flow ◽  
Median Frequency ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Flow Motion

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed “slow-wave flow motion”). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.

scholarly journals Reduction of Functional Capillary Density in Human Brain after Stroke

1990 ◽  
Vol 10 (3) ◽  
pp. 317-326 ◽  
Author(s):  
Albert Gjedde ◽  
Hiroto Kuwabara ◽  
Antoine M. Hakim
Keyword(s):  
Blood Flow ◽  
Brain Tissue ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Functional Density ◽  
Hemodynamic Variables ◽  
Cortical Gray Matter ◽  
Cerebral Ischemic ◽  
Reduced Density

The blood flow of brain tissue often returns to normal after an ischemic episode. As “luxury” rather than “reactive” reperfusion, this hyperemia is associated with low metabolism. It is not known to what extent the high blood flow accompanies a high, normal, or low density of capillaries. The resolution of this question may indicate whether the functional capillary density is variable and, if so, whether it is coupled to blood flow or metabolism. To answer these questions, we defined functional capillaries as capillaries that transport glucose. We then calculated the density of functional capillaries ( Dcap) and the mean time of transit of blood through the capillaries ( tcap) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cerebral ischemic stroke. Each patient was studied twice, within 36 h of the insult and 1 week later. We identified nominally “ischemic” regions in the first study as cortical gray matter regions, contiguous with the ischemic focus, in which the magnitude of blood flow did not exceed 20 ml 100 g−1 min−1. In these regions, values of metabolism and functional capillary density were proportionately low compared with normal values obtained in the contralateral hemisphere. The studies revealed a reduction of the functional density of exchange vessels in postischemic brain tissue as soon as 36 h after the insult. In “ischemic” regions, within 36 h of the insult, the net extraction of oxygen was inversely related to the capillary transit time and appeared to be limited mainly by the low functional density of the capillaries. Contrary to expectations, the reduced density persisted, even when more than adequate perfusion of the tissue returned. For these reasons, we concluded that changes of the capillary density were associated with changes of the metabolism of the tissue rather than with blood flow.

Contribution of Adenosine to the Increase in Skeletal Muscle Blood Flow Caused by Manual Acupuncture in Rats

2017 ◽  
Vol 35 (4) ◽  
pp. 284-288 ◽  
Author(s):  
Hisashi Shinbara ◽  
Satomi Nagaoka ◽  
Yasuyuki Izutani ◽  
Masamichi Okubo ◽  
Keisaku Kimura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Acupuncture Analgesia ◽  
Manual Acupuncture ◽  
Sprague Dawley ◽  
Skeletal Muscle Blood Flow ◽  
Adenosine Receptor Antagonist ◽  
Below The Knee ◽  
Green Fluorescent

Background and aim Adenosine is believed to play an important role in local acupuncture analgesia. The aim of this study was to investigate the contribution of adenosine to the increase in skeletal muscle blood flow (MBF) caused by manual acupuncture (MA). Methods Thirty-two male Sprague-Dawley rats (310–360 g) were anaesthetised and divided into four equal groups (n=8 each): Saline, Saline+MA, Theophylline, and Theophylline+MA. In the two MA groups, the sparrow-pecking MA technique was applied at 30 repetitions per min for 1 min to a depth of 15–18 mm using a stainless steel acupuncture needle (0.20×40 mm). The stimulus point was located on the right tibialis anterior (TA) muscle 7–8 mm below the knee. Animals in the two theophylline groups were intra-arterially injected with 8-(p-sulphophenyl) theophylline, a non-selective adenosine receptor antagonist, at a dose of 30 mg/kg before MA. Animals in the two saline groups received control saline. Fluorescent microspheres (15 µm in diameter, yellow-green fluorescent) were used for MBF measurement in all four groups. Results MA of the TA muscle significantly increased MBF (Saline+MA vs Saline: p=0.001; Saline+MA vs Theophylline: p=0.008). Pre-treatment with theophylline appeared to inhibit this increase (Theophylline vs Theophylline+MA; p=1.000). MBF in the Theophylline+MA group was 43% lower than in the Saline+MA group, although this was not significantly different (p=0.104). Conclusions The results suggest that adenosine leads to an increase in MBF caused by MA. Adenosine may play a role in acupuncture analgesia by washing out algesic substances. Further studies are needed in order to elucidate the precise mechanism.

scholarly journals Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance

2007 ◽  
Vol 112 (8) ◽  
pp. 429-440 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Claudia Scheuer ◽  
Rene Schramm ◽  
...  
Keyword(s):  
Capillary Flow ◽  
Age Groups ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Tissue Necrosis ◽  
Significant Difference ◽  
Ischaemic Necrosis ◽  
Increased Susceptibility ◽  
Capillary Dilation

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2±1 months), adult (10±2 months) and senescent (19±3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5±2.8 μm compared with 3.95±0.79 μm at baseline) and adult (12.1±3.1 μm compared with 3.36±0.45 μm at baseline) animals compared with senescent animals (8.5±1.7 μm compared with 3.28±0.69 μm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0±0 cm/cm2), whereas adult (11.9±13.5 cm/cm2) and, in particular, adolescent animals (58.4±33.6 cm/cm2; P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49±8% (P<0.05) and 42±8% (P<0.05) in senescent and adult animals respectively, compared with 31±6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance.

Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil

1992 ◽  
Vol 263 (3) ◽  
pp. H945-H950 ◽  
Author(s):  
S. P. Sutera ◽  
K. Chang ◽  
J. Marvel ◽  
J. R. Williamson
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Sciatic Nerve ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Citrate Buffer ◽  
Ocular Tissues ◽  
Arterial Blood ◽  
Transit Times ◽  
Sprague Dawley Rats

These studies were undertaken to investigate the relationship between regional hemodynamic and hemorheological changes in the microvasculature of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection of streptozotocin (55 mg/kg body wt). Control rats were injected with vehicle (sodium citrate buffer). A subgroup of diabetic rats was treated with an aldose reductase inhibitor (sorbinil) added to the diet in an amount to provide a daily dose of approximately 0.2 mmol.kg-1.day-1. Three weeks later all animals were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg injected intraperitoneally) for assessment of blood flow (by injection of 15 microns microspheres) and regional hematocrit (determined by isotope-dilution techniques using 51Cr-labeled red blood cells and 125I-labeled bovine serum albumin) in selected tissues. The hematocrit in arterial blood samples was identical (approximately 46%) in controls and in diabetics. Regional hematocrits were much lower than arterial hematocrits in control rats and ranged from approximately 20% in ocular tissues, sciatic nerve, diaphragm, and skin to approximately 30% in brain, skeletal muscle, heart, and fat. Hematocrits of diabetic rats were markedly increased in ocular tissues, sciatic nerve, and skin but not in brain, heart, or skeletal muscle. These increases in regional hematocrit were associated with increases in blood flow and were largely prevented by sorbinil. Diabetes induced significant decreases in the mean transit times for whole blood and erythrocytes in all tissues examined except brain, retina, and skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhagic hypotension induces arteriolar vasomotion and intermittent capillary perfusion in rat pancreas

1994 ◽  
Vol 267 (5) ◽  
pp. H1936-H1940 ◽  
Author(s):  
B. Vollmar ◽  
G. Preissler ◽  
M. D. Menger
Keyword(s):  
Blood Cell ◽  
Microscopic Analysis ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Intravital Fluorescence Microscopy ◽  
Capillary Perfusion ◽  
Induced Hypotension ◽  
Rat Pancreas ◽  
Hemorrhagic Hypotension ◽  
Acinar Tissue

Hemorrhage-induced intermittent capillary perfusion and its relation to arteriolar vasomotion was studied in rat pancreatic acinar tissue using intravital fluorescence microscopy. During prehemorrhage conditions, microscopic analysis of the pancreatic microcirculation displayed neither arteriolar vasomotion nor intermittency of capillary perfusion (n = 22 animals). Hemorrhage-induced hypotension of 40 mmHg provoked arteriolar vasomotion in 18 of 22 animals and 59 of 115 arterioles studied. The maximum relative amplitude of arteriolar vasomotion was 44 +/- 8% (range 12–81%), and vasomotion frequency averaged 4.73 +/- 0.11 cycles/min. Hemorrhagic hypotension was further accompanied by 1) a decrease of functional capillary density [length of red blood cell-perfused capillaries per area of tissue under investigation (cm/cm2)] from 515 +/- 3 cm-1 at baseline to 386 +/- 3 cm-1 (P < 0.05) and 2) the instantaneous occurrence of intermittency of capillary perfusion in all observation areas (N = 220) of the 22 animals studied. The frequency of intermittency of capillary perfusion (4.72 +/- 0.14 cycles/min) did not differ from the frequency of arteriolar vasomotion, which implies a causal relationship between these two hemorrhage-induced microvascular mechanisms with the probable aim to counteract the decrease of functional capillary density.

scholarly journals Therapeutic Angiogenesis by a “Dynamic Duo”: Simultaneous Expression of HGF and VEGF165 by Novel Bicistronic Plasmid Restores Blood Flow in Ischemic Skeletal Muscle

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1231
Author(s):  
Ekaterina Slobodkina ◽  
Maria Boldyreva ◽  
Maxim Karagyaur ◽  
Roman Eremichev ◽  
Natalia Alexandrushkina ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Limb Ischemia ◽  
Bidirectional Promoter ◽  
Capillary Density ◽  
Therapeutic Angiogenesis ◽  
Angiogenic Growth Factors ◽  
Umbilical Vein Endothelial Cells

Therapeutic angiogenesis is a promising strategy for relief of ischemic conditions, and gene delivery was used to stimulate blood vessels’ formation and growth. We have previously shown that intramuscular injection of a mixture containing plasmids encoding vascular endothelial growth factor (VEGF)165 and hepatocyte growth factor (HGF) leads to restoration of blood flow in mouse ischemic limb, and efficacy of combined delivery was superior to each plasmid administered alone. In this work, we evaluated different approaches for co-expression of HGF and VEGF165 genes in a panel of candidate plasmid DNAs (pDNAs) with internal ribosome entry sites (IRESs), a bidirectional promoter or two independent promoters for each gene of interest. Studies in HEK293T culture showed that all plasmids provided synthesis of HGF and VEGF165 proteins and stimulated capillary formation by human umbilical vein endothelial cells (HUVEC), indicating the biological potency of expressed factors. Tests in skeletal muscle explants showed a dramatic difference and most plasmids failed to express HGF and VEGF165 in a significant quantity. However, a bicistronic plasmid with two independent promoters (cytomegalovirus (CMV) for HGF and chicken b-actin (CAG) for VEGF165) provided expression of both grow factors in skeletal muscle at an equimolar ratio. Efficacy tests of bicistronic plasmid were performed in a mouse model of hind limb ischemia. Intramuscular administration of plasmid induced significant restoration of perfusion compared to an empty vector and saline. These findings were supported by increased CD31+ capillary density in animals that received pHGF/VEGF. Overall, our study reports a first-in-class candidate gene therapy drug to deliver two pivotal angiogenic growth factors (HGF and VEGF165) with properties that provide basis for future development of treatment for an unmet medical need—peripheral artery disease and associated limb ischemia.

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