Dissociation between skeletal muscle microvascular Po2and hypoxia-induced microvascular inflammation

2003 ◽  
Vol 94 (6) ◽  
pp. 2323-2329 ◽  
Author(s):  
Sidharth Shah ◽  
Julie Allen ◽  
John G. Wood ◽  
Norberto C. Gonzalez
Keyword(s):  
Blood Flow ◽  
Microvascular Blood Flow ◽  
Phosphorescence Quenching ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Systemic Hypoxia ◽  
Individual Contributions ◽  
Microvascular Inflammation ◽  
Quenching Method ◽  
The Individual

Systemic hypoxia (SHx) produces microvascular inflammation in mesenteric, cremasteric, and pial microcirculations. In anesthetized rats, SHx lowers arterial blood pressure (MABP), which may alter microvascular blood flow and microvascular Po2(PmO2) and influence SHx-induced leukocyte-endothelial adherence (LEA). These experiments attempted to determine the individual contributions of the decreases in PmO2, venular blood flow and shear rate, and MABP to the hypoxia-induced increase in LEA. Cremaster microcirculation of anesthetized rats was visualized by intravital microscopy. PmO2was measured by a phosphorescence-quenching method. SHx [inspired Po2of 70 Torr for 10 min, MABP of 65 ± 3 mmHg, arterial Po2(PaO2) of 33 ± 1 Torr] and cremaster ischemia (MABP of 111 ± 7 mmHg, PaO2of 86 ± 3 Torr) produced similar PmO2: 7 ± 2 and 6 ± 2 Torr, respectively. However, LEA increased only in SHx (1.9 ± 0.9 vs. 11.2 ± 1.1 leukocytes/100 μm, control vs. SHx, P < 0.05). Phentolamine-induced hypotension (MABP of 55 ± 4 mmHg) in normoxia lowered PmO2to 26 ± 6 Torr but did not increase LEA. Cremaster equilibration with 95% N2-5% CO2during air breathing (PaO2of 80 ± 1 Torr) lowered PmO2to 6 ± 1 Torr but did not increase LEA. On the other hand, when cremaster PmO2was maintained at 60–70 Torr during SHx (PaO2of 35 ± 1 Torr), LEA increased from 2.1 ± 1.1 to 11.1 ± 1.5 leukocytes/100 μm ( P < 0.05). The results show a dissociation between PmO2and LEA and support the idea that SHx results in the release of a mediator responsible for the inflammatory response.

A model of anemic tissue perfusion after blood transfusion shows critical role of endothelial response to shear stress stimuli

2021 ◽  
Author(s):  
Weiyu Li ◽  
Amy G. Tsai ◽  
Marcos Intaglietta ◽  
Daniel M. Tartakovsky
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Blood Transfusion ◽  
Critical Role ◽  
Cardiovascular Responses ◽  
Arterial Blood Flow ◽  
Microvascular Blood Flow ◽  
No Production ◽  
Arterial Blood ◽  
Transfusion Requirements

­­ ­Although some of the cardiovascular responses to changes in hematocrit (Hct) are not fully quantified experimentally, available information is sufficient to build a mathematical model of the consequences of treating anemia by introducing RBCs into the circulation via blood transfusion. We present such a model, which describes how the treatment of normovolemic anemia with blood transfusion impacts oxygen (O2) delivery (DO2, the product of blood O2 content and arterial blood flow) by the microcirculation. Our analysis accounts for the differential response of the endothelium to the wall shear stress (WSS) stimulus, changes in nitric oxide (NO) production due to modification of blood viscosity caused by alterations of both hematocrit (Hct) and cell free layer thickness, as well as for their combined effects on microvascular blood flow and DO2. Our model shows that transfusions of 1- and 2-unit of blood have a minimal effect on DO2 if the microcirculation is unresponsive to the WSS stimulus for NO production that causes vasodilatation increasing blood flow and DO2. Conversely, in a fully WSS responsive organism, blood transfusion significantly enhances blood flow and DO2, because increased viscosity stimulates endothelial NO production causing vasodilatation. This finding suggests that evaluation of a patients' pre-transfusion endothelial WSS responsiveness should be beneficial in determining the optimal transfusion requirements for treating anemic patients.

Age-related changes in regional blood flow in the rat

1985 ◽  
Vol 249 (3) ◽  
pp. H485-H491 ◽  
Author(s):  
R. F. Tuma ◽  
G. L. Irion ◽  
U. S. Vasthare ◽  
L. A. Heinel
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Index ◽  
Regional Blood Flow ◽  
Adult Rats ◽  
Blood Flows ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Regional Blood Flows ◽  
Central Hemodynamic

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.

Activation of mast cells by systemic hypoxia, but not by local hypoxia, mediates increased leukocyte-endothelial adherence in cremaster venules

2003 ◽  
Vol 95 (6) ◽  
pp. 2495-2502 ◽  
Author(s):  
Randy Dix ◽  
Teresa Orth ◽  
Julie Allen ◽  
John G. Wood ◽  
Norberto C. Gonzalez
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Selective Reduction ◽  
Mast Cell Activation ◽  
Phosphorescence Quenching ◽  
Inflammatory Cascade ◽  
Systemic Hypoxia ◽  
Quenching Method ◽  
Short Time

Systemic hypoxia, produced by lowering inspired Po2, induces a rapid inflammation in several microcirculations, including cremaster muscle. Mast cell activation is a necessary element of this response. Selective reduction of cremaster microvascular Po2(PmO2) with normal systemic arterial Po2(PaO2; cremaster hypoxia/systemic normoxia), however, does not elicit increased leukocyte-endothelial adherence (LEA) in cremaster venules. This could be due to a short time of leukocyte exposure to the hypoxic cremaster environment. Conversely, LEA increases when PaO2is lowered, while cremaster PmO2remains high (cremaster normoxia/systemic hypoxia). An alternative explanation of these results is that a mediator released from a central site during systemic hypoxia initiates the inflammatory cascade. We hypothesized that if this is the case, cremaster mast cells would be activated during cremaster normoxia/systemic hypoxia, but not during cremaster hypoxia/systemic normoxia. The microcirculation of rat cremaster muscles was visualized by using intravital microscopy. Cremaster PmO2was measured with a phosphorescence quenching method. Cremaster hypoxia/systemic normoxia (PmO27 ± 1 Torr, PaO287 ± 2 Torr) did not increase LEA; however, topical application of the mast cell activator compound 48/80 under these conditions did increase LEA. The effect of compound 48/80 on LEA was blocked by topical cromolyn, a mast cell stabilizer. LEA increased during cremaster normoxia/systemic hypoxia, (PmO264 ± 5 Torr, PaO233 ± 2 Torr); this increase was blocked by topical cromolyn. The results suggest that mast cell stimulation occurs only when PaO2is reduced, independent of cremaster PmO2, and support the idea of a mediator that is released during systemic hypoxia and initiates the inflammatory cascade.

Microvascular hematocrit and red cell flow in resting and contracting striated muscle

1979 ◽  
Vol 237 (4) ◽  
pp. H481-H490 ◽  
Author(s):  
B. Klitzman ◽  
B. R. Duling
Keyword(s):  
Blood Flow ◽  
Oxygen Supply ◽  
Striated Muscle ◽  
Volume Fraction ◽  
Plasma Layer ◽  
Element Model ◽  
Microvascular Blood Flow ◽  
Red Cell ◽  
Total Blood ◽  
Arterial Blood

Microvascular hematocrit and its possible relation to oxygen supply were systematically examined. We studied the red cell volume fraction (hematocrit) in arterial blood and in capillaries under a variety of circumstances. Control capillary hematocrit averaged 10.4 +/- 2.0% (SE) and arteriolar (14.2 micrometer ID) hematocrit averaged 13.9 +/- 1.2% in cremaster muscles of pentobarbital-anesthetized hamsters. Carotid artery hematocrit was 53.2 +/- 0.6%. The low microvessel hematocrit could not be entirely explained by a high red cell flux through arteriovenous channels other than capillaries (shunting). Hematocrit was not only low at rest, but varied with physiological stimuli. A 1-Hz muscle contraction increased capillary hematocrit to 18.5 +/- 2.4%, and maximal vasodilation induced a rise to 39.3 +/- 9.5%. The quantitative relations between capillary red cell flux, arterial hematocrit, and total blood flow could be explained by a two-element model of microvascular blood flow that incorporated a relatively slow-moving plasma layer (1.2 micrometer). Such a model would generate a low microvessel hematocrit and might reduce the diffusion capacity of individual capillaries, but would not reduce time-averaged red cell flux or alter steady-state vascular oxygen supply.

scholarly journals Topical Menthol, Ice, Peripheral Blood Flow, and Perceived Discomfort

2013 ◽  
Vol 48 (2) ◽  
pp. 220-225 ◽  
Author(s):  
Robert Topp ◽  
Elizabeth R. Ledford ◽  
Dean E. Jacks
Keyword(s):  
Blood Flow ◽  
Radial Artery ◽  
Peripheral Blood ◽  
Arterial Blood Flow ◽  
Microvascular Blood Flow ◽  
Artery Blood Flow ◽  
Arterial Diameter ◽  
Arterial Blood ◽  
Treatment Conditions ◽  
Crushed Ice

Context Injury management commonly includes decreasing arterial blood flow to the affected site in an attempt to reduce microvascular blood flow and edema and limit the induction of inflammation. Applied separately, ice and menthol gel decrease arterial blood flow, but the combined effects of ice and menthol gel on arterial blood flow are unknown. Objectives To compare radial artery blood flow, arterial diameter, and perceived discomfort before and after the application of 1 of 4 treatment conditions. Design Experimental crossover design. Setting Clinical laboratory. Participants or Other Participants Ten healthy men, 9 healthy women (mean age = 25.68 years, mean height = 1.73 m, mean weight = 76.73 kg). Intervention(s) Four treatment conditions were randomly applied for 20 minutes to the right forearm of participants on 4 different days separated by at least 24 hours: (1) 3.5 mL menthol gel, (2) 0.5 kg of crushed ice, (3) 3.5 mL of menthol gel and 0.5 kg of crushed ice, or (4) no treatment (control). Main Outcome Measure(s) Using high-resolution ultrasound, we measured right radial artery diameter (cm) and blood flow (mL/min) every 5 minutes for 20 minutes after the treatment was applied. Discomfort with the treatment was documented using a 1-to-10 intensity scale. Results Radial artery blood flow decreased (P &lt; .05) from baseline in the ice (−20% to −24%), menthol (−17% to −24%), and ice and menthol (−36% to −39%) treatments but not in the control (3% to 9%) at 5, 10, and 15 minutes. At 20 minutes after baseline, only the ice (−27%) and combined ice and menthol (−38%) treatments exhibited reductions in blood flow (P &lt; .05). Discomfort was less with menthol than with the ice treatment at 5, 10, and 20 minutes after application (P &lt; .05). Arterial diameter and heart rate did not change. Conclusions The application of 3.5 mL of menthol was similar to the application of 0.5 kg of crushed ice in reducing peripheral blood flood. Combining crushed ice with menthol appeared to have an additive effect on reducing blood flow.

Effects of hypoxia and hypercapnia on whole body release and clearance of choline

1995 ◽  
Vol 268 (6) ◽  
pp. R1520-R1525 ◽  
Author(s):  
D. J. Jenden ◽  
O. U. Scremin
Keyword(s):  
Simple Model ◽  
Intravenous Infusion ◽  
Respiratory Acidosis ◽  
Whole Body ◽  
Body Balance ◽  
Arterial Blood ◽  
Individual Contributions ◽  
Per Se ◽  
The Individual

We have recently demonstrated an increase in arterial blood choline (Ch) concentration in normocapnic hypoxia and apnea. This could be due to enhanced release of free Ch from tissues, to decreased Ch clearance, or both. The present investigations was undertaken to determine the individual contributions of these processes to the whole body balance of Ch, using an intravenous infusion of tracer quantities of [2H4]Ch to assess the bidirectional flux between the central pool and peripheral pools. Rats were subjected to normocapnic hypoxia or hypercapnia; release and clearance of Ch were calculated using a simple model. Hypoxia caused an increase in Ch production and a decrease in Ch clearance. At severe levels of hypoxia, Ch clearance was essentially zero. Hypoxia was attended by progressive acidosis that was related to the magnitude of the hypoxic challenge. To determine the possible effects of acidosis per se on the variables measured, respiratory acidosis with normoxia was provoked by controlled administration of CO2. Under these conditions, parallel decreases in Ch production and Ch clearance were observed.

scholarly journals High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men

2020 ◽  
Vol 318 (6) ◽  
pp. E1014-E1021 ◽  
Author(s):  
Lewan Parker ◽  
Dale J. Morrison ◽  
Andrew C. Betik ◽  
Katherine Roberts-Thomson ◽  
Gunveen Kaur ◽  
...  
Keyword(s):  
Blood Flow ◽  
Blood Glucose ◽  
High Glucose ◽  
Young Men ◽  
Arterial Blood Flow ◽  
Thigh Muscle ◽  
Microvascular Blood Flow ◽  
Arterial Blood ◽  
Glucose Ingestion ◽  
Meal Ingestion

Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF), which may contribute to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load would prevent postprandial MBF dysfunction. Ten healthy young men (age, 27 yr [24, 30], mean with lower and upper bounds of the 95% confidence interval; height, 180 cm [174, 185]; weight, 77 kg [70, 84]) ingested a high-glucose (1.1 g/kg glucose) mixed-nutrient meal (10 kcal/kg; 45% carbohydrate, 20% protein, and 35% fat) in the morning after an overnight fast. Femoral arterial blood flow was measured via Doppler ultrasound, and thigh MBF was measured via contrast-enhanced ultrasound, before meal ingestion and 1 h and 2 h postprandially. Blood glucose and plasma insulin were measured at baseline and every 15 min throughout the 2-h postprandial period. Compared with baseline, thigh muscle microvascular blood volume, velocity, and flow were significantly impaired at 60 min postprandial (−25%, −27%, and −46%, respectively; all P < 0.05) and to a greater extent at 120 min postprandial (−37%, −46%, and −64%; all P < 0.01). Heart rate and femoral arterial diameter, blood velocity, and blood flow were significantly increased at 60 min and 120 min postprandial (all P < 0.05). Higher blood glucose area under the curve was correlated with greater MBF dysfunction ( R2 = 0.742; P < 0.001). Ingestion of a high-glucose mixed-nutrient meal impairs MBF in healthy individuals for up to 2 h postprandial.

Exercise training prevents the inflammatory response to hypoxia in cremaster venules

2005 ◽  
Vol 98 (6) ◽  
pp. 2113-2118 ◽  
Author(s):  
Teresa A. Orth ◽  
Julie A. Allen ◽  
John G. Wood ◽  
Norberto C. Gonzalez
Keyword(s):  
Shear Rate ◽  
Exercise Training ◽  
Fluorescence Intensity ◽  
Intensity Ratio ◽  
Leukocyte Count ◽  
Fluorescence Intensity Ratio ◽  
Systemic Hypoxia ◽  
Microvascular Inflammation ◽  
Quenching Method ◽  
Blood Leukocyte

Systemic hypoxia produces microvascular inflammation in several tissues, including skeletal muscle. Exercise training (ET) has been shown to reduce the inflammatory component of several diseases. Alternatively, ET could influence hypoxia-induced inflammation by improving tissue oxygenation or increasing mechanical antiadhesive forces at the leukocyte-endothelial interface. The effect of 5 wk of treadmill ET on hypoxia-induced microvascular inflammation was studied in the cremaster microcirculation of rats using intravital microscopy. In untrained rats, hypoxia (arterial Po2 = 32.3 ± 2.1 Torr) increased leukocyte-endothelial adherence from 2.3 ± 0.4 to 10.2 ± 0.3 leukocytes per 100 μm of venule ( P < 0.05) and was accompanied by extravasation of FITC-labeled albumin after 4 h of hypoxia (extra-/intravascular fluorescence intensity ratio = 0.50 ± 0.07). These responses were attenuated in ET (leukocyte adherence was 1.5 ± 0.4 during normoxia and 1.8 ± 0.7 leukocytes per 100 μm venule after 10 min of hypoxia; extra-/intravascular fluorescence intensity ratio = 0.11 ± 0.02; P < 0.05 vs. untrained) despite similar reductions of arterial (32.4 ± 1.8 Torr) and microvascular Po2 (measured with an oxyphor-quenching method) in both groups. Shear rate decreased during hypoxia to similar extents in ET and untrained rats. In addition, circulating blood leukocyte count was similar in ET and untrained rats. The effects of ET on hypoxia-induced leukocyte-endothelial adherence remained up to 4 wk after discontinuing training. Thus ET attenuated hypoxia-induced inflammation despite similar effects of hypoxia on tissue Po2, venular shear rate, and circulating leukocyte count.

scholarly journals Increased hemoglobin O2 affinity protects during acute hypoxia

2012 ◽  
Vol 303 (3) ◽  
pp. H271-H281 ◽  
Author(s):  
Ozlem Yalcin ◽  
Pedro Cabrales
Keyword(s):  
Blood Flow ◽  
Acute Hypoxia ◽  
Severe Hypoxia ◽  
Microvascular Blood Flow ◽  
Vehicle Group ◽  
Control Group ◽  
Arterial Blood ◽  
Partial Pressures ◽  
Chamber Model ◽  
Window Chamber

Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence oxygen (O2) transport and O2 utilization. Although decreasing hemoglobin (Hb) O2 affinity would favor the release of O2 to the tissues, increasing Hb O2 affinity would augment arterial O2 saturation during hypoxia. This study was designed to test the hypothesis that pharmacologically increasing the Hb O2 affinity will augment O2 transport during severe hypoxia (10 and 5% inspired O2) compared with normal Hb O2 affinity. RBC Hb O2 affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals received only the vehicle. The effects of increasing Hb O2 affinity were studied in the hamster window chamber model, in terms of systemic and microvascular hemodynamics and partial pressures of O2 (Po2). Pimonidazole binding to hypoxic areas of mice heart and brain was also studied. 5HMF decreased the Po2 at which the Hb is 50% saturated with O2 by 12.6 mmHg. During 10 and 5% O2 hypoxia, 5HMF increased arterial blood O2 saturation by 35 and 48% from the vehicle group, respectively. During 5% O2 hypoxia, blood pressure and heart rate were 58 and 30% higher for 5HMF compared with the vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. Consequently, perivascular Po2 was three times higher in the 5HMF group compared with the control group at 5% O2 hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. Therefore, increased Hb O2 affinity resulted in hemodynamics and oxygenation benefits during severe hypoxia. This acute acclimatization process may have implications in survival during severe environmental hypoxia when logistic constraints prevent chronic acclimatization.

scholarly journals Selective Electrical Stimulation of Postganglionic Cerebrovascular Parasympathetic Nerve Fibers Originating from the Sphenopalatine Ganglion Enhances Cortical Blood Flow in the Rat

1990 ◽  
Vol 10 (3) ◽  
pp. 383-391 ◽  
Author(s):  
Norihiro Suzuki ◽  
Jan Erik Hardebo ◽  
Jan Kåhrström ◽  
Christer Owman
Keyword(s):  
Blood Flow ◽  
Electrical Stimulation ◽  
Nerve Fibers ◽  
Microvascular Blood Flow ◽  
Sphenopalatine Ganglion ◽  
Flow Measurements ◽  
Parasympathetic Nerve ◽  
Cortical Blood Flow ◽  
Arterial Blood ◽  
Stimulation Of

Recently, the origins and pathways of cerebrovascular acetylcholine- and vasoactive intestinal polypeptide-containing nerves have been elucidated in detail in the rat: The sphenopalatine ganglion is the major source for postganglionic parasympathetic fibers to the vascular beds of the cerebral hemispheres. To clarify the functional role of the nerves on cerebral blood vessels in vivo, brain cortical microvascular blood flow was measured in rats during electrical stimulation of these particular postganglionic fibers. Animals were subjected to transection of the right nasociliary nerve 2 weeks before the flow measurements to eliminate activation of peptidergic sensory fibers. Relative change in microvascular blood flow was continuously recorded by a laser-Doppler flowmeter system under α-chloralose anesthesia. The postganglionic fibers were electrically stimulated just proximal to the ethmoidal foramen by a bipolar platinum electrode (5 V; 0.5 ms; 3, 10, 30, 60 Hz; as a continuous stimulation for 90 s). Stimulation at 10 Hz induced a marked increase of the cortical blood flow (CoBF) on the ipsilateral side, whereas no change was observed on the contralateral side. It reached a maximum mean value of 42.5% at 46 s, and then slightly declined during the remaining stimulation period. No significant changes were observed in the mean arterial blood pressure or blood gases during or after stimulation. Both atropine and scopolamine failed to alter this flow increase. Electrical stimulation of the postganglionic fibers at different frequencies revealed a maximal increase in the CoBF at 30 Hz in the control situation (47.2%), but at 10 Hz after scopolamine administration (51.6%). This provides the first report showing that selective postganglionic stimulation of the parasympathetic nerve fibers markedly enhances blood flow in the brain, and it supports the view that the neurogenic vasodilatation is primarily noncholinergic.

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