Estimating oxygen consumption rates of arteriolar walls under physiological conditions in rat skeletal muscle

2005 ◽  
Vol 289 (1) ◽  
pp. H295-H300 ◽  
Author(s):  
Masahiro Shibata ◽  
Shigeru Ichioka ◽  
Akira Kamiya
Keyword(s):  
Vascular Tone ◽  
Consumption Rate ◽  
Vascular Wall ◽  
Surrounding Tissue ◽  
Phosphorescence Quenching ◽  
Physiological Conditions ◽  
First Order ◽  
Vascular Walls ◽  
Consumption Rates

To examine the effects of vascular tone reduction on O2 consumption of the vascular wall, we determined the O2 consumption rates of arteriolar walls under normal conditions and during vasodilation induced by topical application of papaverine. A phosphorescence quenching technique was used to quantify intra- and perivascular Po2 in rat cremaster arterioles with different branching orders. Then, the measured radial Po2 gradients and a theoretical model were used to estimate the O2 consumption rates of the arteriolar walls. The vascular O2 consumption rates of functional arterioles were >100 times greater than those observed in in vitro experiments. The vascular O2 consumption rate was highest in first-order (1A) arterioles, which are located upstream, and sequentially decreased downstream in 2A and 3A arterioles under normal conditions. During papaverine-induced vasodilation, on the other hand, the O2 consumption rates of the vascular walls decreased to similar levels, suggesting that the high O2 consumption rates of 1A arterioles under normal conditions depend in part on the workload of the vascular smooth muscle. These results strongly support the hypothesis that arteriolar walls consume a significant amount of O2 compared with the surrounding tissue. Furthermore, the reduction of vascular tone of arteriolar walls may facilitate an efficient supply of O2 to the surrounding tissue.

Abstract 238: Oxygen Regulates the Flux of Nitric Oxide Diffusion across the Vascular Wall

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Xiaoping Liu ◽  
Parthasarathy Srinivasan ◽  
Eric Collard ◽  
Paula Grajdeanu ◽  
Jay L Zweier ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oxygen Concentration ◽  
Rate Constant ◽  
Aortic Wall ◽  
Vascular Wall ◽  
Surrounding Tissue ◽  
Diffusion Distance ◽  
First Order ◽  
No Consumption ◽  
Oxygen Concentrations

Endothelium-derived nitric oxide (NO) plays an important role in maintaining vascular tone. It is known that NO may be consumed by heme proteins, superoxide and oxygen during diffusion from the endothelium to smooth muscle cells in the vascular wall. Due to the limitation of available techniques, it is unclear to what extent these consumptions can affect the diffusion distance of NO, and if the vascular NO consumption could serve as a “sensor” of oxygen concentrations in the blood vessels. In this study, rat aortas were used as an experimental model for studying NO diffusion process in the vascular system. A Clark-type NO electrode was used to directly measure the flux of NO diffusion across the vascular wall at 37 °C. A segment of aorta was isolated from a 12-week old WKY rat. After the aorta was cleaned and surrounding tissue was removed, it was longitudinally opened. A specifically-designed aorta holder was attached on the tip of the Clark-type NO electrode. The aorta holder surface and the electrode tip surface were aligned in the same plane so that the opened aorta segment could be placed flat on the electrode tip surface and pinned to the aorta holder. Using this technique, we measured the flux of NO diffusion across the aortic wall at different oxygen concentration. It was observed that the NO flux increased 6 to 10 fold when oxygen concentrations dropped from 200 μM to zero. A mathematical model describing the steady-state diffusion-reaction was used in analyzing the experimental data. It was found that the rate of NO decay is first order with respect to [O 2 ] and first order with respect to [NO], and hence of the form k[O 2 ][NO]. The rate constant k was determined as (3.8±0.4)x10 −3 μM −1 s −1 (n=6). With this rate constant, the half-life of NO in the aortic wall in the presence of 200 μM O 2 (equilibrium with room air) will be 0.9 seconds. Our results show that the flux and diffusion distance of NO in the aortic wall is largely regulated by oxygen concentration. When oxygen concentrations drop, NO diffusion distance will significantly increase. As a result, the blood vessel will dilate to a larger extent to allow more blood to be delivered to the hypoxic tissues. Therefore this vascular NO consumption appears to play the role of an oxygen sensor in the regulation of blood flow in the body.

Thrombin Does Not Alter Vascular Hyporeactivity in Models of Endotoxin-Induced Septic Shock in Rats

1995 ◽  
Vol 88 (2) ◽  
pp. 149-157 ◽  
Author(s):  
Viviane Martin ◽  
Marie-Louise Wiesel ◽  
Anne Albert ◽  
Alain Beretz
Keyword(s):  
Nitric Oxide ◽  
Disseminated Intravascular Coagulation ◽  
Vascular Tone ◽  
Endotoxic Shock ◽  
Vascular Wall ◽  
Anticoagulant Treatment ◽  
Intravascular Coagulation ◽  
Vascular Hyporeactivity

1. Hypotension and vascular hyporesponsiveness to vasoconstrictors are observed during endotoxic shock, and are associated with increased production of nitric oxide in the vascular wall. Disseminated intravascular coagulation is another feature of septicaemia. We hypothesized that thrombin generated during disseminated intravascular coagulation might modulate the changes in vascular tone induced by endotoxin. 2. Incubation of rat aortic rings for 4 h with α-thrombin (0.003–3.0 NIH units/ml) did not change their reactivity to noradrenaline. Incubation for 4 h with lipopolysaccharide increased the EC50 for noradrenaline, whereas co-incubation of thrombin (0.5 NIH units/ml) with lipopolysaccharide did not alter this hyporeactivity to noradrenaline. 3. In vivo in rats, lipopolysaccharide caused early (1 h) and late (4–6 h) hyporeactivity to noradrenaline. In rats infused with lipopolysaccharide and heparin (1 U min−1 kg−1, 0.4 ml/h) or hirudin (2.2 mg ml−1 kg−1, 0.8 ml/h), vasopressor responses to noradrenaline were not different from those after infusion of lipopolysaccharide alone. Aortic rings taken from rats receiving both anticoagulant treatment and lipopolysaccharide had the same sensitivity to noradrenaline as those obtained from rats receiving lipopolysaccharide alone. 4. Our results suggest that, in vivo, disseminated intravascular coagulation does not modify the early and late effects of lipopolysaccharide on arterial pressure and that, in vitro, thrombin neither induces hyporeactivity to noradrenaline nor modifies lipopolysaccharide-induced hyporeactivity. We propose that thrombin generated during disseminated intravascular coagulation in rats does not play a major role in the alterations of vascular tone observed during endotoxic shock.

scholarly journals The rate of O2 loss from mesenteric arterioles is not unusually high

2011 ◽  
Vol 301 (3) ◽  
pp. H737-H745 ◽  
Author(s):  
Aleksander S. Golub ◽  
Bjorn K. Song ◽  
Roland N. Pittman
Keyword(s):  
Respiration Rate ◽  
Volume Fraction ◽  
Vascular Wall ◽  
Surrounding Tissue ◽  
Disappearance Rate ◽  
Estimation Of Parameters ◽  
Phosphorescence Quenching ◽  
Rat Mesentery ◽  
Exponential Decline ◽  
Arteriolar Wall

The O2 disappearance curve (ODC) recorded in an arteriole after the rapid arrest of blood flow reflects the complex interaction among the dissociation of O2 from hemoglobin, O2 diffusivity, and rate of respiration in the vascular wall and surrounding tissue. In this study, the analysis of experimental ODCs allowed the estimation of parameters of O2 transport and O2 consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM). The technique was used to prevent the artifact of accumulated O2 photoconsumption in stationary media. The observed ODC signatures were close to linear, in contrast to the reported exponential decline of intra-arteriolar Po2. The rate of Po2 decrease was 0.43 mmHg/s in 20-μm-diameter arterioles. The duration of the ODC was 290 s, much longer than the 12.8 s reported by other investigators. The arterioles associated with lymphatic microvessels had a higher O2 disappearance rate of 0.73 mmHg/s. The O2 flux from arterioles, calculated from the average O2 disappearance rate, was 0.21 nl O2·cm−2·s−1, two orders of magnitude lower than reported in the literature. The physical upper limit of the O2 consumption rate by the arteriolar wall, calculated from the condition that all O2 is consumed by the wall, was 452 nl O2·cm−3·s−1. From consideration of the microvascular tissue volume fraction in the rat mesentery of 6%, the estimated respiration rate of the vessel wall was ∼30 nl O2·cm−3·s−1. This result was three orders of magnitude lower than the respiration rate in rat mesenteric arterioles reported by other investigators. Our results demonstrate that O2 loss from mesenteric arterioles is small and that the O2 consumption by the arteriolar wall is not unusually large.

Microvascular and interstitial Po 2measurements in rat skeletal muscle by phosphorescence quenching

2001 ◽  
Vol 91 (1) ◽  
pp. 321-327 ◽  
Author(s):  
Masahiro Shibata ◽  
Shigeru Ichioka ◽  
Joji Ando ◽  
Akira Kamiya
Keyword(s):  
Skeletal Muscle ◽  
Sole Source ◽  
Surrounding Tissue ◽  
Systemic Blood ◽  
Significant Drop ◽  
Phosphorescence Quenching ◽  
Tissue Interface ◽  
Different Diameters

To clarify the transport of O2 across the microvessels in skeletal muscle, we designed an intravital laser microscope that utilizes a phosphorescence quenching technique to determine both the microvascular and tissue Po 2. After we injected the phosphorescent probe into systemic blood, phosphorescence excited by a N2-dye pulse laser was detected with a photomultiplier over a 10 μm in diameter area. In vitro and in vivo calibrations confirmed that the present method is accurate for Po 2measurements in the range of 7–90 Torr ( r= 0.958) and has a rapid response time. This method was then used to measure the Po 2 of microvessels with different diameters (40–130 μm) and of interstitial spaces in rat cremaster muscle. These measurements showed a significant drop in Po 2 in the arterioles after branching (from 74.6 to 46.6 Torr) and the presence of a large Po 2 gradient at the blood-tissue interface of arterioles (15–20 Torr). These findings suggest that capillaries are not the sole source of oxygen supply to surrounding tissue.

Pathophysiology of Thrombosis in Peripheral Artery Disease

2020 ◽  
Vol 18 (3) ◽  
pp. 204-214 ◽  
Author(s):  
Aida Habib ◽  
Giovanna Petrucci ◽  
Bianca Rocca
Keyword(s):  
Vascular Tone ◽  
Platelet Reactivity ◽  
Coagulation Factors ◽  
Peripheral Artery ◽  
Antithrombotic Agents ◽  
Pharmacological Interventions ◽  
Physiological Conditions ◽  
Vasoactive Mediators ◽  
Artery Disease

<P>Under physiological conditions, peripheral arteries release endogenous vascular-protective and antithrombotic agents. Endothelial cells actively synthesize vasoactive mediators, which regulate vascular tone and platelet reactivity thus preventing thrombosis. Atherosclerosis disrupts homeostasis and favours thrombosis by triggering pro-thrombotic responses in the vessels, platelet activation, aggregation as well as vasoconstriction, phenomena that ultimately lead to symptomatic lumen restriction or complete occlusion. <P> In the present review, we will discuss the homeostatic role of arterial vessels in releasing vascular-protective agents, such as nitric oxide and prostacyclin, the role of pro- and anti-thrombotic vascular receptors as well as the contribution of circulating platelets and coagulation factors in triggering the pro-thrombotic response(s). We will discuss the pathological consequences of disrupting the protective pathways in the arteries and the pharmacological interventions along these pathways.</P>

In-vitro Kinetic Hydrolysis Study of Metronidazole Derivatives with Carvacrol and Eugenol Using Validated RP-HPLC Method

2020 ◽  
Vol 16 ◽  
Author(s):  
M. Alarjah
Keyword(s):  
Half Life ◽  
Hplc Method ◽  
Hydrolysis Rate ◽  
First Order ◽  
First Order Kinetics ◽  
Rp Hplc ◽  
Pharmacokinetic Properties ◽  
Pseudo First Order ◽  
Kinetic Hydrolysis

Background: Prodrugs principle is widely used to improve the pharmacological and pharmacokinetic properties of some active drugs. Much effort was made to develop metronidazole prodrugs to enhance antibacterial activity and or to improve pharmacokinetic properties of the molecule or to lower the adverse effects of metronidazole. Objective: In this work, the pharmacokinetic properties of some of monoterpenes and eugenol pro metronidazole molecules that were developed earlier were evaluated in-vitro. The kinetic hydrolysis rate constants and half-life time estimation of the new metronidazole derivatives were calculated using the validated RP-HPLC method. Method: Chromatographic analysis was done using Zorbbax Eclipse eXtra Dense Bonding (XDB)-C18 column of dimensions (250 mm, 4.6 mm, 5 μm), at ambient column temperature. The mobile phase was a mixture of sodium dihydrogen phosphate buffer of pH 4.5 and methanol in gradient elution, at 1ml/min flow rate. The method was fully validated according to the International Council for Harmonization (ICH) guidelines. The hydrolysis process carried out in an acidic buffer pH 1.2 and in an alkaline buffer pH 7.4 in a thermostatic bath at 37ºC. Results: The results followed pseudo-first-order kinetics. All metronidazole prodrugs were stable in the acidic pH, while they were hydrolysed in the alkaline buffer within a few hours (6-8 hr). The rate constant and half-life values were calculated, and their values were found to be 0.082- 0.117 hr-1 and 5.9- 8.5 hr., respectively. Conclusion: The developed method was accurate, sensitive, and selective for the prodrugs. For most of the prodrugs, the hydrolysis followed pseudo-first-order kinetics; the method might be utilised to conduct an in-vivo study for the metronidazole derivatives with monoterpenes and eugenol.

scholarly journals Development and Evaluation of Fluoxetine Fast Dissolving Films: An Alternative for Noncompliance in Pediatric Patients

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 778
Author(s):  
Emőke-Margit Rédai ◽  
Paula Antonoaea ◽  
Nicoleta Todoran ◽  
Robert Alexandru Vlad ◽  
Magdalena Bîrsan ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Hydroxypropyl Methylcellulose ◽  
Pharmaceutical Formulations ◽  
Release Kinetic ◽  
Disintegration Time ◽  
Casting Technique ◽  
First Order ◽  
Orodispersible Films ◽  
Folding Endurance

The most used pharmaceutical formulations for children are syrups, suppositories, soft chewable capsules, and mini-tablets. Administrating them might create an administration discomfort. This study aimed to develop and evaluate orodispersible films (ODFs) for pediatric patients in which the fluoxetine (FX) is formulated in the polymeric matrix. Six FX fast dissolving films (10 mg FX/ODF), FX1, FX2, FX3, FX4, FX5, and FX6, were prepared by solvent casting technique. In the composition of the ODFs, the concentration of the hydroxypropyl methylcellulose and the concentration of the propylene glycol were varied. Each formulation of fluoxetine ODF was evaluated by determining the tensile strength, folding endurance, disintegration, behavior in the controlled humidity and temperature conditions, and adhesiveness. All the obtained results were compared with the results obtained for six ODFs prepared without FX. The disintegration time of the FX ODFs was of maximum 88 s for FX2. Via the in vitro releasing study of the FX from the ODFs it was noticed that FX1 and FX2 allow a better release of the drug 99.98 ± 3.81% and 97.67 ± 3.85% being released within 15 min. From the obtained results it was also confirmed that FX ODFs were found to follow first-order release kinetic.

scholarly journals Injectable non-leaching tissue-mimetic bottlebrush elastomers as an advanced platform for reconstructive surgery

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erfan Dashtimoghadam ◽  
Farahnaz Fahimipour ◽  
Andrew N. Keith ◽  
Foad Vashahi ◽  
Pavel Popryadukhin ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Reconstructive Surgery ◽  
Biomedical Applications ◽  
The Body ◽  
Surrounding Tissue ◽  
Curing Time ◽  
Materials Used ◽  
Significant Health

AbstractCurrent materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.

scholarly journals Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets

2021 ◽  
Vol 22 (16) ◽  
pp. 8367
Author(s):  
Hien Lau ◽  
Shiri Li ◽  
Nicole Corrales ◽  
Samuel Rodriguez ◽  
Mohammadreza Mohammadi ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Oxygen Consumption ◽  
Insulin Secretion ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
In Vitro Development ◽  
Porcine Islets ◽  
Vitro Development

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8–15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

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