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      Intermittent compression induces transitory hypoxic stimuli, upstream vasodilation and enhanced perfusion of skin capillaries, independent of age and diabetes

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          Abstract

          This study demonstrates that hand intermittent pneumatic compression evokes transitory hypoxic stimuli in distal finger skin microcirculation inducing vasodilation of arterial inflow vessels, enhanced perfusion, and maximum capillary recruitment in young and older subjects and older subjects with type 2 diabetes mellitus. Enhanced shear stress in the microcirculation did not appear to induce local skin vasodilation.

          Abstract

          The benefit of enhanced shear stress to the vascular endothelium has been well-documented in conduit arteries but is less understood in skin microcirculation. The aim of this study was to provide physiological evidence of the vascular changes in skin microcirculation induced by intermittent pneumatic compression (IPC) of 1 s cuff inflation (130 mmHg) every 20 s to the palm of the hand for 30 min. The oxygenation and hemodynamics of dorsal mid-phalangeal finger skin microcirculation were assessed by laser Doppler fluximetry and reflectance spectroscopy before, during, and after IPC in 15 young (18-39 years old) and 39 older (40–80 years old) controls and 32 older subjects with type 2 diabetes mellitus. Each individual cuff inflation induced: 1) brief surge in flux immediately after cuff deflation followed by 2) transitory reduction in blood oxygen for ∼4 s, and 3) a second increase in perfusion and oxygenation of the microcirculation peaking ∼11 s after cuff deflation in all subject groups. With no significant change in blood volume observed by reflectance spectroscopy, despite the increased shear stress at the observed site, this second peak in flux and blood oxygen suggests a delayed vasoactive response upstream inducing increased arterial influx in the microcirculation that was higher in older controls and subjects with diabetes compared to young controls ( P < 0.001, P < 0.001, respectively) and achieving maximum capillary recruitment in all subject groups. Transitory hypoxic stimuli with conducted vasodilation may be a mechanism through which IPC enhances capillary perfusion in skin microcirculation independent of age and type 2 diabetes mellitus.

          NEW & NOTEWORTHY This study demonstrates that hand intermittent pneumatic compression evokes transitory hypoxic stimuli in distal finger skin microcirculation inducing vasodilation of arterial inflow vessels, enhanced perfusion, and maximum capillary recruitment in young and older subjects and older subjects with type 2 diabetes mellitus. Enhanced shear stress in the microcirculation did not appear to induce local skin vasodilation.

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          Most cited references 67

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          Endothelial Function and Dysfunction: Testing and Clinical Relevance

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            Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.

            Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondrial content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH oxidase activity of mitochondrial electron transport chain (ETC), and activity of citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD), key enzymes of TCA cycle and beta-oxidation pathway, respectively. Frozen biopsies collected from obese or T2DM individuals in our previous studies were used to estimate activity of beta-HAD. The obtained data were complemented by data from our previous studies and statistically analyzed to compare mitochondrial content and mitochondrial enzyme profile in lean, obese, or T2DM cohort. The total activity of NADH oxidase was reduced significantly in obese or T2DM subjects. The cardiolipin content for lean or obese group was similar, and although for T2DM group cardiolipin showed a tendency to decline, it was statistically insignificant. The total activity of citrate synthase for lean and T2DM group was similar; however, it was increased significantly in the obese group. Activity of beta-HAD and mtDNA content was similar for all three groups. We conclude that the total activity of NADH oxidase in biopsy for lean group is significantly higher than corresponding activity for obese or T2DM cohort. The specific activity of NADH oxidase (per mg cardiolipin) and NADH oxidase/citrate synthase and NADH oxidase/beta-HAD ratios are reduced two- to threefold in both T2DM and obesity.
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              Hypoxic modulation of exogenous nitrite-induced vasodilation in humans.

              It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia. Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 mumol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8+/-3.4% (mean+/-SEM) at 7.84 micromol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04+/-0.09 (baseline) to 1.62+/-0.18 (nitrite; P<0.05) versus 1.07+/-0.09 (baseline) to 2.37+/-0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings. Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Journal of Applied Physiology
                Journal of Applied Physiology
                American Physiological Society
                8750-7587
                1522-1601
                April 01 2021
                April 01 2021
                : 130
                : 4
                : 1072-1084
                Affiliations
                [1 ]Diabetes and Vascular Medicine, Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, College of Medicine and Health and NIHR Exeter Clinical Research Facility, and School of Physics and Astronomy, University of Exeter, Exeter, United Kingdom
                Article
                10.1152/japplphysiol.00657.2020
                8f1a9b10-0f16-4fa4-879a-cd11b9439905
                © 2021

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