Effect of peroxynitrite on plasma extravasation, microvascular blood flow and nociception in the rat

Nitric oxide (NO) has been shown to be a potent vasodilator released from endothelial cells (EC) in large blood vessels, but NO release has not been examined in the capillary bed. Because the capillary bed represents the largest source of EC, it may be the largest source of vascular NO. In the present study, we used intravital microscopy to examine the effect of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on the microvasculature of the rat extensor digitorum longus muscle. L-NAME (30 mM) applied locally to a capillary (300 micron(s) from the feeding arteriole) reduced red blood cell (RBC) velocity [VRBC; control VRBC = 238 +/- 58 (SE) micron/s; delta VRBC = -76 +/- 8%] and RBC flux (4.4 +/- 0.7 to 2.8 +/- 0.7 RBC/s) significantly in the capillary, but did not change feeding arteriole diameter (Dcon = 6.3 +/- 0.7 micron, delta D = 5 +/- 7%) or draining venule diameter (Dcon = 10.1 +/- 0.6 micron, delta D = 4 +/- 2%). Because of the VRBC change, the flux reduction was equivalent to an increased local hemoconcentration from 1.8 to 5 RBCs per 100 micron capillary length. L-NAME also caused an increase in the number of adhering leukocytes in the venule from 0.29 to 1.43 cells/100 micron. L-NAME (30 mM) applied either to arterioles or to venules did not change capillary VRBC. Bradykinin (BK) locally applied to the capillary caused significant increases in VRBC (delta VRBC = 111 +/- 23%) and in arteriolar diameter (delta D = 40 +/- 5%). This BK response was blocked by capillary pretreatment with 30 mM L-NAME (delta VRBC = -4 +/- 27%; delta D = 5 +/- 9% after BK). We concluded that NO may be released from capillary EC both basally and in response to the vasodilator BK. We hypothesize that 1) low basal levels of NO affect capillary blood flow by modulating local hemoconcentration and leukocyte adhesion, and 2) higher levels of NO (stimulated by BK) may cause a remote vasodilation to increase microvascular blood flow.

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Two-step machine learning method for the rapid analysis of microvascular flow in intravital video microscopy

Scientific Reports ◽

10.1038/s41598-021-89469-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ossama Mahmoud ◽

Mahmoud El-Sakka ◽

Barry G. H. Janssen

Keyword(s):

Machine Learning ◽

Blood Flow ◽

Human Error ◽

Image Data ◽

Video Microscopy ◽

Microvascular Blood Flow ◽

Image Processing Algorithm ◽

Step Algorithm ◽

3D Cnn

AbstractMicrovascular blood flow is crucial for tissue and organ function and is often severely affected by diseases. Therefore, investigating the microvasculature under different pathological circumstances is essential to understand the role of the microcirculation in health and sickness. Microvascular blood flow is generally investigated with Intravital Video Microscopy (IVM), and the captured images are stored on a computer for later off-line analysis. The analysis of these images is a manual and challenging process, evaluating experiments very time consuming and susceptible to human error. Since more advanced digital cameras are used in IVM, the experimental data volume will also increase significantly. This study presents a new two-step image processing algorithm that uses a trained Convolutional Neural Network (CNN) to functionally analyze IVM microscopic images without the need for manual analysis. While the first step uses a modified vessel segmentation algorithm to extract the location of vessel-like structures, the second step uses a 3D-CNN to assess whether the vessel-like structures have blood flowing in it or not. We demonstrate that our two-step algorithm can efficiently analyze IVM image data with high accuracy (83%). To our knowledge, this is the first application of machine learning for the functional analysis of microvascular blood flow in vivo.

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On the poro-elastic models for microvascular blood flow resistance: An in vitro validation

Journal of Biomechanics ◽

10.1016/j.jbiomech.2021.110241 ◽

2021 ◽

Vol 117 ◽

pp. 110241

Author(s):

Alberto Coccarelli ◽

Supratim Saha ◽

Tanjeri Purushotham ◽

K. Arul Prakash ◽

Perumal Nithiarasu

Keyword(s):

Blood Flow ◽

Flow Resistance ◽

Microvascular Blood Flow

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Age-Related Changes in Microvascular Blood Flow and Transcutaneous Oxygen Tension Under Basal and Stimulated Conditions

The Journals of Gerontology Series A ◽

10.1093/gerona/60.2.200 ◽

2005 ◽

Vol 60 (2) ◽

pp. 200-206 ◽

Cited By ~ 28

Author(s):

Rajna Ogrin ◽

Peteris Darzins ◽

Zeinab Khalil

Keyword(s):

Blood Flow ◽

Oxygen Tension ◽

Microvascular Blood Flow ◽

Transcutaneous Oxygen Tension ◽

Transcutaneous Oxygen ◽

Age Related ◽

Age Related Changes

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cGMP phosphodiesterase inhibition improves the vascular and metabolic actions of insulin in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00691.2010 ◽

2011 ◽

Vol 301 (2) ◽

pp. E342-E350 ◽

Cited By ~ 13

Author(s):

A. J. Genders ◽

E. A. Bradley ◽

S. Rattigan ◽

S. M. Richards

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Glucose Uptake ◽

Mrna Level ◽

Microvascular Perfusion ◽

Microvascular Blood Flow ◽

Whole Body ◽

Acute Administration ◽

Dependent Inhibition ◽

Promising Avenue

There is considerable support for the concept that insulin-mediated increases in microvascular blood flow to muscle impact significantly on muscle glucose uptake. Since the microvascular blood flow increases with insulin have been shown to be nitric oxide-dependent inhibition of cGMP-degrading phosphodiesterases (cGMP PDEs) is predicted to enhance insulin-mediated increases in microvascular perfusion and muscle glucose uptake. Therefore, we studied the effects of the pan-cGMP PDE inhibitor zaprinast on the metabolic and vascular actions of insulin in muscle. Hyperinsulinemic euglycemic clamps (3 mU·min−1·kg−1) were performed in anesthetized rats and changes in microvascular blood flow assessed from rates of 1-methylxanthine metabolism across the muscle bed by capillary xanthine oxidase in response to insulin and zaprinast. We also characterized cGMP PDE isoform expression in muscle by real-time PCR and immunostaining of frozen muscle sections. Zaprinast enhanced insulin-mediated microvascular perfusion by 29% and muscle glucose uptake by 89%, while whole body glucose infusion rate during insulin infusion was increased by 33% at 2 h. PDE2, -9, and -10 were the major isoforms expressed at the mRNA level in muscle, while PDE1B, -9A, -10A, and -11A proteins were expressed in blood vessels. Acute administration of the cGMP PDE inhibitor zaprinast enhances muscle microvascular blood flow and glucose uptake response to insulin. The expression of a number of cGMP PDE isoforms in skeletal muscle suggests that targeting specific cGMP PDE isoforms may provide a promising avenue for development of a novel class of therapeutics for enhancing muscle insulin sensitivity.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00524.2021 ◽

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.

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Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00234.2018 ◽

2018 ◽

Vol 315 (6) ◽

pp. E1242-E1250 ◽

Cited By ~ 1

Author(s):

Donghua Hu ◽

Ryan D. Russell ◽

Devika Remash ◽

Timothy Greenaway ◽

Stephen Rattigan ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Flow ◽

Adipose Tissue ◽

Resistance Training ◽

Blood Volume ◽

Fasting Blood Glucose ◽

Microvascular Blood Flow ◽

Oral Glucose ◽

Model Assessment

The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

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