Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre)

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

British Journal of Pharmacology ◽

10.1038/sj.bjp.0701498 ◽

1997 ◽

Vol 122 (6) ◽

pp. 1083-1088 ◽

Cited By ~ 30

Author(s):

V. C. Ridger ◽

S. A. B. Greenacre ◽

R. L. C. Handy ◽

B. Halliwell ◽

P. K. Moore ◽

...

Keyword(s):

Blood Flow ◽

Microvascular Blood Flow ◽

Plasma Extravasation

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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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