Blood Cell Flux Research Articles

Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans.

What is the central question of this study? The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress. What is the main finding and its importance? The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population. African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10mm ascorbic acid or 10μm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) at a rate of 2.0μlmin-1 . Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax ) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23±4years old) subjects participated. During 39°C heating, the %CVCmax was lower in AA at the control (CA, 65±20% versus AA, 47±15%; P<0.05) and ascorbic acid sites (CA, 73±14% versus AA: 49±17%; P<0.01). At the tempol site, there were no differences between groups. This was followed by infusion of 10mm l-NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with tempol. These data suggest that: (i)cutaneous vasodilatation in response to local heating is blunted in AA relative to CA; and (ii)elevated superoxide generation attenuates nitric oxide-mediated cutaneous vasodilatation in AA.

Impact of Temporal Heterogeneity of Acute Hypoxia on the Radiation Response of Experimental Tumors.

Tumor hypoxia is a major factor inducing resistance to radiotherapy. Spatial limitation in oxygen (O2) diffusion usually leads to chronic hypoxia, whereas temporary shut-down of perfusion or fluctuations in red blood cell flux can cause acute hypoxia. Since the role of temporal heterogeneity of pO2 in acute hypoxia during radiotherapy remains unclear, this study focuses on analyzing the influence of temporal heterogeneity of tumor hypoxia upon radiotherapy by modeling the temporal variance of acute hypoxia. The computational simulation was conducted on digital 2D tumor phantoms. The O2 diffusion and consumption within the tumor tissues were calculated using the reaction-diffusion equation. A total of nine experimental tumor lines (FaDu, GL, C3H, RIF, SCCVII, KHT, MEF, MTG, HT29) were modeled according to known pO2 distributions. Each tumor line was first simulated 36 times with various temporal heterogeneities (dynamic hypoxia) and once again without temporal heterogeneity (static hypoxia). Temporal pO2 fluctuations were modeled according to known red blood cell (RBC) fluxes. All tumor phantoms were irradiated with 30 fractions of 2 Gy. Cell survival was calculated as a function of pO2 and radiation dose via linear quadratic model. The simulation results indicate that the temporal heterogeneity varies with different tumor types, and tumor line HT29 shows the most significant impact of temporal heterogeneity upon the treatment effect. The ratio between the surviving fractions without and with temporal variance ranges from 1.44 to 6.28. Given the same mean pO2, the fraction of killed tumor cells in dynamic hypoxia is higher than in static hypoxia. A temporal heterogeneity index (THI) denoting normalized average pO2 temporal variance is proposed. The results show that for similar mean tumor pO2, a strong inverse correlation between THI and the surviving fraction is observed for each tumor line. THI is highly proportional to the fraction of acute hypoxia and to the RBC flux. The proposed THI corresponds well to the fraction of acute hypoxia.

Spatio-temporal dynamics of cerebral capillary segments with stalling red blood cells

Optical coherence tomography (OCT) allows label-free imaging of red blood cell (RBC) flux within capillaries with high spatio-temporal resolution. In this study, we utilized time-series OCT-angiography to demonstrate interruptions in capillary RBC flux in mouse brain in vivo. We noticed ∼7.5% of ∼200 capillaries had at least one stall in awake mice with chronic windows during a 9-min recording. At any instant, ∼0.45% of capillaries were stalled. Average stall duration was ∼15 s but could last over 1 min. Stalls were more frequent and longer lasting in acute window preparations. Further, isoflurane anesthesia in chronic preparations caused an increase in the number of stalls. In repeated imaging, the same segments had a tendency to stall again over a period of one month. In awake animals, functional stimulation decreased the observance of stalling events. Stalling segments were located distally, away from the first couple of arteriolar-side capillary branches and their average RBC and plasma velocities were lower than nonstalling capillaries within the same region. This first systematic analysis of capillary RBC stalls in the brain, enabled by rapid and continuous volumetric imaging of capillaries with OCT-angiography, will lead to future investigations of the potential role of stalling events in cerebral pathologies.

Ten days of repeated local forearm heating does not affect cutaneous vascular function.

The aim of the present study was to determine whether 10 days of repeated local heating could induce peripheral adaptations in the cutaneous vasculature and to investigate potential mechanisms of adaptation. We also assessed maximal forearm blood flow to determine whether repeated local heating affects maximal dilator capacity. Before and after 10 days of heat training consisting of 1-h exposures of the forearm to 42°C water or 32°C water (control) in the contralateral arm (randomized and counterbalanced), we assessed hyperemia to rapid local heating of the skin (n = 14 recreationally active young subjects). In addition, sequential doses of acetylcholine (ACh, 1 and 10 mM) were infused in a subset of subjects (n = 7) via microdialysis to study potential nonthermal microvascular adaptations following 10 days of repeated forearm heat training. Skin blood flow was assessed using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as laser-Doppler red blood cell flux divided by mean arterial pressure. Maximal cutaneous vasodilation was achieved by heating the arm in a water-spray device for 45 min and assessed using venous occlusion plethysmography. Forearm vascular conductance (FVC) was calculated as forearm blood flow divided by mean arterial pressure. Repeated forearm heating did not increase plateau percent maximal CVC (CVCmax) responses to local heating (89 ± 3 vs. 89 ± 2% CVCmax, P = 0.19), 1 mM ACh (43 ± 9 vs. 53 ± 7% CVCmax, P = 0.76), or 10 mM ACh (61 ± 9 vs. 85 ± 7% CVCmax, P = 0.37, by 2-way repeated-measures ANOVA). There was a main effect of time at 10 mM ACh (P = 0.03). Maximal FVC remained unchanged (0.12 ± 0.02 vs. 0.14 ± 0.02 FVC, P = 0.30). No differences were observed in the control arm. Ten days of repeated forearm heating in recreationally active young adults did not improve the microvascular responsiveness to ACh or local heating.NEW & NOTEWORTHY We show for the first time that 10 days of repeated forearm heating is not sufficient to improve cutaneous vascular responsiveness in recreationally active young adults. In addition, this is the first study to investigate cutaneous cholinergic sensitivity and forearm blood flow following repeated local heat exposure. Our data add to the limited studies regarding repeated local heating of the cutaneous vasculature.

Micro-vascular Blood Flow During Post-Occlusive Reactive Hyperemia Assessed By Diffuse Correlation Spectroscopy

PURPOSE: The purpose of this investigation was to determine if Diffuse Correlation Spectroscopy (DCS) provides a reproducible measure of micro-vascular blood flux during post-occlusive reactive hyperemia (PORH). Previous techniques utilized to assess forearm muscle blood flow include brachial artery blood flow and Near Infrared Spectroscopy (NIRS). DCS provides a novel ability to examine red blood cell (RBC) flux within the muscle microvasculature. We hypothesized that DCS would provide a reproducible measure of muscle microvasculature RBC flux during PORH. METHODS: 7 healthy male subjects (25.9 ± 4 yrs) performed 3 trials of brachial artery PORH tests. The DCS probe was placed on the flexor digitorum superficialis m. of the cuffed arm and provided Blood Flow Index (BFI). Brachial artery blood flow was assessed using Doppler Ultrasound to provide time-averaged maximum velocity (TAMAX). Following a 10 min supine rest period baseline measurements were performed for 1 min at which time a pneumatic cuff was inflated to at least 250 mmHg for 5 minutes. Measurements continued to be made for the 5 min of occlusion and 3 min post cuff release. The subjects were given 10 min rest between trials. RESULTS: The peak TAMAX of the brachial artery for PORH1, PORH2, and PORH3 occurred at 7.3 ± 3.4, 6.0 ± 2.4, and 6.4 ± 2.7 sec respectively (p=0.397). The peak in BFI for PORH1, PORH2, and PORH3 occurred at 25.6 ± 4.5, 26.4 ± 8.3, and 22.3 ± 3.5 sec respectively (p=0.311). The time to peak for TAMAX was significantly different from the time to peak in BFI (p<0.001). CONCLUSIONS: Similar time to peak for BFI across trials indicates that the DCS provides a reproducible signal of muscle microvasculature blood flux during PORH conditions. We speculate that the significant difference between time to peak for TAMAX and BFI may be due to compliance between the brachial artery and the microvasculature.

Influence of Ischaemia‐Reperfusion Injury on Sensory Nerve Control of Vasodilation During a Subsequent Bout of Local Skin Heating in the Forearm

Cutaneous sensory nerves play a vital role in moderating microcirculatory blood flow by releasing vasodilatory neuropeptides in response to various stimuli including local heating. Ischaemia‐reperfusion (I‐R) injury is associated with altered sensory nerve conduction and depletion of sensory neuropeptide stores, which may contribute to an impaired vasodilatory response to local skin heating following the initial ischemic insult. In ten participants we evaluated the contribution of sensory nerves in driving the vasodilatory response to local heating in forearm skin before and after 20 minutes of ischaemia induced by inflating (220 mmHg) a standard blood pressure cuff around the arm. Red blood cell flux, an index of skin blood flow, was examined using laser‐Doppler probes with integrated local heating units. Flux values were then divided by mean arterial pressure and reported as cutaneous vascular conductance (CVC). Local heating was initiated prior to ischaemia and 20 minutes after the release of cuff occlusion at separate skin sites. At each site local temperature was controlled at 33°C and then increased (3°C min−1) to 42°C and held for ~30 min. Following this, local temperature was increased to 44°C for 20 min. Responses were compared between sites with sensory nerves blocked via local anaesthetic (EMLA) cream and untreated (UNTR) sites before and after I‐R. At UNTR sites, I‐R itself had no effect on CVC during the initial vasodilation (5%; P&gt;0.05). However, relative to the UNTR site before I‐R, EMLA reduced CVC during the initial vasodilation by 45% before ischaemia and 20% after I‐R (both P&lt;0.05). Neither I‐R nor EMLA treatment altered CVC during the secondary plateau at 42°C or at maximum heating to 44°C (all P&gt;0.05). I‐R injury caused a significant delay in vasodilatory onset of 36% (P&lt;0.05) at the UNTR site compared to delays of ~76% at EMLA sites before and after I‐R (both P&lt;0.05). The time to initial vasodilatory peak between UNTR sites was unchanged by I‐R (2%; P&gt;0.05). Conversely, it was significantly delayed by 24% (P&lt;0.05) with EMLA application before I‐R, but not after (17%; P&gt;0.05). We conclude that cutaneous sensory nerve impairment caused by 20 minutes of forearm I‐R injury significantly impairs the kinetics of the response to a rapid, non‐painful local heating stimulus, which may be associated with a higher temperature threshold for initiating vasodilation post‐ischaemia. This alteration of sensory nerve function may contribute to persistent tissue hypoxia and impaired thermoregulatory responses to local skin or whole body heating following an initial ischemic insult if temperature is not adequately controlled.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada: Discovery Grant (227912‐12, S.S. Cheung)

Label free measurement of retinal blood cell flux, velocity, hematocrit and capillary width in the living mouse eye.

Measuring blood cell dynamics within the capillaries of the living eye provides crucial information regarding the health of the microvascular network. To date, the study of single blood cell movement in this network has been obscured by optical aberrations, hindered by weak optical contrast, and often required injection of exogenous fluorescent dyes to perform measurements. Here we present a new strategy to non-invasively image single blood cells in the living mouse eye without contrast agents. Eye aberrations were corrected with an adaptive optics camera coupled with a fast, 15 kHz scanned beam orthogonal to a capillary of interest. Blood cells were imaged as they flowed past a near infrared imaging beam to which the eye is relatively insensitive. Optical contrast of cells was optimized using differential scatter of blood cells in the split-detector imaging configuration. Combined, these strategies provide label-free, non-invasive imaging of blood cells in the retina as they travel in single file in capillaries, enabling determination of cell flux, morphology, class, velocity, and rheology at the single cell level.

Evaluation of surface blood flow in intact and ruptured canine cruciate ligaments using laser Doppler flowmetry.

To evaluate the usefulness of laser Doppler flowmetry (LDF) to measure surface blood flow in canine cruciate ligaments, compare measurements in different sites of intact and partially ruptured canine cranial cruciate ligaments (CrCL) and intact caudal cruciate ligaments (CaCL), and investigate any association between surface blood flow in partially ruptured CrCL and synovitis or duration of clinical signs. Case-controlled clinical study. Sixteen dogs with partially ruptured CrCL and five dogs with intact CrCL. Blood cell flux (BCF) readings during three measurement cycles using LDF at two sites in each ligament (mid-substance and the distal portion of the CrCL, and mid-substance and the proximal portion of the CaCL) were recorded. Synovial changes were graded grossly and histologically using the Osteoarthritis Research Society International histopathology scoring system. The within-run coefficients of variation (CV) for a single BCF measurement cycle were 12.2% and 12.7% in the ruptured and intact CrCL groups, respectively. The between-run CV for three measurement cycles was 20.8% and 14.8%, respectively. The intraclass correlation coefficient (ICC, absolute agreement) was 0.66 for a single measurement cycle and 0.86 for the average of three cycles. No difference in average BCF readings was found between any two sites in either group, but BCF readings in both CrCL sites were significantly higher in the ruptured CrCL group than the intact CrCL group. No associations between BCF and synovial grades or duration of lameness were identified. Laser Doppler flowmetry can be used to assess surface blood flow in intact and partially ruptured canine cruciate ligaments with acceptable precision. Using this method, surface blood flow appears greater in partially ruptured canine CrCL than intact CrCL. Further studies are required to determine if this is a sequela of trauma or synovitis.

Optical coherence tomography in the assessment of acute changes in cutaneous vascular diameter induced by heat stress.

There are limited imaging technologies available that can accurately assess or provide surrogate markers of the in vivo cutaneous microvessel network in humans. In this study, we establish the use of optical coherence tomography (OCT) as a novel imaging technique to assess acute changes in cutaneous microvessel area density and diameter in humans. OCT speckle decorrelation images of the skin on the ventral side of the forearm up to a depth of 500 μm were obtained prior to and following 20-25 min of lower limb heating in eight healthy men [30.3 ± 7.6 (SD) yr]. Skin red blood cell flux was also collected using laser Doppler flowmetry probes immediately adjacent to the OCT skin sites, along with skin temperature. OCT speckle decorrelation images were obtained at both baseline and heating time points. Forearm skin flux increased significantly (0.20 ± 0.15 to 1.75 ± 0.38 cutaneous vascular conductance, P < 0.01), along with forearm skin temperature (32.0 ± 1.2 to 34.3 ± 1.0°C, P < 0.01). Quantitative differences in the automated calculation of vascular area densities (26 ± 9 to 49 ± 19%, P < 0.01) and individual microvessel diameters (68 ± 17 to 105 ± 25 μm, P < 0.01) were evident following the heating session. This is the first in vivo within-subject assessment of acute changes in the cutaneous microvasculature in response to heating in humans and highlights the use of OCT as an exciting new imaging approach for skin physiology and clinical research.

Effect of stump parameters on postural stability during clinical tests in transtibial and transfemoral amputees

Pressure ulcers are a major healthcare problem and caused by pressure and shear-forces. Although shear-force is understood to be a major contributing factor, no preventive interventions are specifically aimed at relieving the effect of shear on skin to improve skin viability.A physical model was used to apply a combined loading of 2.4 kPa pressure and 14.5 N shear-force on skin in humans. Loading was applied on the volar aspect of both forearms for 30 min in ten healthy volunteers. One arm received loading on skin with a wound dressing, the other arm (control) received loading directly on skin. The following parameters were determined before and after loading: IL-1α/Total Protein-ratio (used as a measure of skin damage); Cutaneous blood cell flux ((CBF) measure of reactive hyperaemia); Lactate concentration (measure of tissue ischemia).Three different dressings were tested on three different days. The order of dressing application, dressing arm and start of the intervention were randomized.Participants mean age was 22.5±1.6 year with a BMI of 22.3±2.4 kg/m2. IL-1α/Total Protein-ratio of the skin was significantly lower after the application of pressure and shear when the Mepilex® (P<0.01), Allevyn (P<0.05) or AquacelTM dressing (P<0.01) was used compared with the control measurement. The Mepilex® dressing was more effective in reducing post-load IL-1α/Total Protein-ratio compared to the Allevyn dressing (P<0.01).Post-load CBF was significantly lower when the Mepilex® or Aquacel dressing was used (P<0.001). Both dressings induced significantly less post-load CBF than the Allevyn dressing (P<0.01 and P<0.001, respectively).The concentration of lactate was not significantly increased after the application of pressure and shear and could not be used as a measure with this model.This is the first in vivo study to demonstrate that the effects of pressure in combination with shear on skin viability can be improved with foam dressings. In this study, the multi-layered dressings perform better than the single-layered dressing.

Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice

We employed optical coherence tomography to measure cerebral cortical capillary red blood cell (RBC) flux in mice. The results suggest that baseline-flux weakly depends on cortical depth. Furthermore, under hypercapnia, low baseline-flux capillaries exhibit greater flux increases while the higher ones saturate, resulting in RBC-flux homogenization. Power-spectrum analysis indicates that higher flux capillaries saw greater flux variability in the low-frequency range (0.01–0.1 Hz) both at baseline and during hypercapnia. These results suggest that lower baseline-flux capillaries have more reserve to deliver oxygen with increased blood flow; but higher ones more strongly impact the low-frequency fluctuations associated with BOLD fMRI measurements of resting state functional connectivity.

Acute Cheese Consumption Ameliorates Sodium-Induced Cutaneous Microvascular Dysfunction by Reducing Ascorbate-Sensitive Oxidants

In epidemiological studies, chronic dairy intake is associated with improved cardiovascular outcomes; conversely, high dietary sodium (Na) consumption impairs endothelial function through increased oxidative stress and reduced nitric oxide (NO)-dependent mechanisms. PURPOSE: To examine if the high Na in cheese has a less negative effect on microvascular dysfunction relative to equivalent Na from non-dairy sources due to the actions of milk-based macronutrients and proteins. We hypothesized that 1) acute dairy based cheese ingestion augments NO-dependent vasodilation (VD) compared to an equal amount of Na from non-dairy sources, and 2) the Na-induced decrease in NO-dependent VD is mediated by oxidant stress mechanisms. METHODS: On 5 separate visits, 14 subjects (61±2 yrs) consumed either 85 g cheddar cheese (560 mg Na), 85 g soy cheese (560 mg Na), 65 g pretzels (560 mg Na), 170 g cheddar cheese (1120 mg Na), or 130 g pretzels (1120 mg Na). Two intradermal microdialysis fibers were inserted in the forearm skin for local delivery of 1) lactated Ringer’s solution (control site) and 2) ascorbate (antioxidant site). Red blood cell flux was measured by laser-Doppler flowmetry (LDF) during local skin heating (42°C) to induce endothelial NO synthase-dependent VD. Once a plateau in cutaneous vascular conductance (CVC = LDF/MAP) occurred, 20 mM L-NAME was perfused at both sites to directly quantify NO-dependent VD. Data were expressed as a percentage of maximum (%CVCmax; 28mM SNP). RESULTS: The total vasodilatory response was not different among the five dietary treatments. NO-dependent VD was higher following dairy cheese consumption compared to a Na-equivalent in soy cheese (59±5 vs. 44±6%; p=0.03) or pretzels (560 mg Na: 59±5 vs. 45±4%; p=0.03, 1120 mg Na: 57±4 vs. 46±5%; p=0.02). Local ascorbate administration abolished these differences (no main dietary treatment effect). CONCLUSION: Na ingestion in cheese was associated with a higher NO-dependent VD compared to an equal amount of non-dairy Na, a difference that was abolished with a local non-specific antioxidant. These data suggest that macronutrients in dairy based cheese may protect against acute Na-induced microvascular dysfunction through antioxidant mechanisms. Supported by Dairy Management Inc.

Tempol Augments the Blunted Cutaneous Microvascular Thermal Reactivity in Healthy Young African Americans

African Americans (AA) have a higher risk for a variety of cardiovascular and metabolic diseases including hypertension, stroke, peripheral artery disease, and type 2 diabetes mellitus when compared with Caucasian Americans (CA). While this elevated risk is multifactorial impaired vascular endothelial function is a contributing factor. In this study, we hypothesized that cutaneous hyperemic response to a standard local heating protocol is reduced in young AA when compared with CA. We further hypothesized that tempol (a superoxide dismutase mimetic) would increase this cutaneous vasodilatory response to local heating in AA. Microdialysis fibers were randomly assigned to receive 1) lactated Ringer's solution (Control), 2) 10 mM ascorbic acid, or 3) 10 μM 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (Tempol) at a rate of 2.0 μl/min. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C plus sodium nitroprusside administration. Twenty‐four (12 AA, 12 CA) young (23 ± 4 years of age) and healthy (body mass index (24.3 ± 2.8 kg/m2) subjects participated in the study. At the Control site, there were no differences between groups for baseline %CVCmax during resting without heat (P = 0.275). During 33 °C, there were still no differences in %CVCmax between groups (P = 0.107); however, %CVCmax at 39 °C was lower in AA when compared with CA (P &lt; 0.001). At the ascorbic acid site, there were no differences between groups for both baseline %CVCmax during resting without heat (P = 0.549) and %CVCmax during 33 °C (P = 0.120); however, %CVCmax at 39 °C was attenuated in AA relative to CA (P &lt; 0.001). At tempol site, there were no differences between groups for all phases including baseline CVC during resting without heat (P = 0.791), %CVCmax during 33 °C (P = 0.550), and %CVCmax at 39 °C (P = 0.948). These data suggest that 1) cutaneous vasodilation in response to local heating is blunted in AA relative to CA. 2) in AA, elevated O2− generation attenuates cutaneous vasodilation when heat is directly applied to the skin.Support or Funding InformationInstitutional start‐up funds from The University of Texas at Austin

Improving the effect of shear on skin viability with wound dressings

BackgroundPressure ulcers are a major healthcare problem and caused by pressure and shear-forces. Although shear-force is understood to be a major contributing factor, no preventive interventions are specifically aimed at relieving the effect of shear on skin to improve skin viability. MethodsA physical model was used to apply a combined loading of 2.4kPa pressure and 14.5N shear-force on skin in humans. Loading was applied on the volar aspect of both forearms for 30min in ten healthy volunteers. One arm received loading on skin with a wound dressing, the other arm (control) received loading directly on skin. The following parameters were determined before and after loading: IL-1α/Total Protein-ratio (used as a measure of skin damage); Cutaneous blood cell flux ((CBF) measure of reactive hyperaemia); Lactate concentration (measure of tissue ischemia).Three different dressings were tested on three different days. The order of dressing application, dressing arm and start of the intervention were randomized. ResultsParticipants mean age was 22.5±1.6 year with a BMI of 22.3±2.4kg/m2. IL-1α/Total Protein-ratio of the skin was significantly lower after the application of pressure and shear when the Mepilex® (P<0.01), Allevyn (P<0.05) or AquacelTM dressing (P<0.01) was used compared with the control measurement. The Mepilex® dressing was more effective in reducing post-load IL-1α/Total Protein-ratio compared to the Allevyn dressing (P<0.01).Post-load CBF was significantly lower when the Mepilex® or Aquacel dressing was used (P<0.001). Both dressings induced significantly less post-load CBF than the Allevyn dressing (P<0.01 and P<0.001, respectively).The concentration of lactate was not significantly increased after the application of pressure and shear and could not be used as a measure with this model. ConclusionThis is the first in vivo study to demonstrate that the effects of pressure in combination with shear on skin viability can be improved with foam dressings. In this study, the multi-layered dressings perform better than the single-layered dressing.

Temporal changes in tumor oxygenation and perfusion upon normo- and hyperbaric inspiratory hyperoxia.

Inspiratory hyperoxia under hyperbaric conditions has been shown to effectively reduce tumor hypoxia and to improve radiosensitivity. However, applying irradiation (RT) under hyperbaric conditions is technically difficult in the clinical setting since RT after decompression may be effective only if tumor pO2 remains elevated for a certain period of time. The aim of the present study was to analyze the time course of tumor oxygenation and perfusion during and after hyperbaric hyperoxia. Tumor oxygenation, red blood cell (RBC) flux for perfusion monitoring, and vascular resistance were assessed continuously in experimental rat DS-sarcomas by polarographic catheter electrodes and laser Doppler flowmetry at 1 and 2 atm (bar) of environmental pressure during breathing of pure O2 or carbogen (95 % O2 + 5 % CO2). During room air breathing, the tumor pO2 followed very rapidly within a few minutes the change of the ambient pressure during compression or decompression. With O2 breathing under hyperbaric conditions, the tumor pO2 increased more than expected based on the rise of the environmental pressure, although the time course was comparably rapid. Breathing carbogen, the tumor pO2 followed with a slight delay of the pressure change, and within 10 min after decompression the baseline values were reached again. RBC flux increased during carbogen breathing but remained almost constant with pure O2, indicating a vasodilation (decrease in vascular resistance) with carbogen but a vasoconstriction (increase in vascular resistance) with O2 during hyperbaric conditions. Since the tumor pO2 directly followed the environmental pressure, teletherapy after hyperbaric conditions does not seem to be promising as the pO2 reaches baseline values again within 5-10 min after decompression.

Early capillary flux homogenization in response to neural activation

This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery.

Simultaneously Measuring Red Blood Cell Flux in vivo for a Large Number of Retinal Capillary Vessels Using Optical Coherence Tomography

Simultaneously Measuring Red Blood Cell Flux in vivo for a Large Number of Retinal Capillary Vessels Using Optical Coherence Tomography

Post‐Occlusive Reactive Hyperemia: Effects on Skeletal Muscle Capillary Hemodynamics

Post‐occlusive reactive hyperemia (PORH) is the commonly accepted non‐invasive diagnostic test used for evaluating endothelial function in humans. In contrast to conduit brachial artery blood flow, little is known regarding capillary hemodynamics during PORH. An understanding of microcirculatory behavior post occlusion is fundamental to interpreting the PORH response. Based on previous results found in humans we tested the hypothesis that mechanically induced ischemia of the spinotrapezius muscle would increase the percentage of capillaries supporting red blood cell (RBC) flux during reperfusion. Capillary hemodynamics were measured via intravital microscopy in young male Sprague‐Dawley rats at baseline (BL), during mechanical feed artery occlusion (OCC, 1 min and 5 min) and subsequent reperfusion. Mean arterial pressure and heart rate were not altered (both P &gt; 0.05). As expected, the percentage of capillaries supporting RBC flux was reduced during 1 min OCC (BL: 90 ± 3, OCC: 2 ± 2%, P &lt; 0.05) and 5 min OCC (BL: 87 ± 3, OCC: 0 ± 0%, P &lt;0.05). At 30 s reperfusion the percentage of capillaries supporting RBC flux decreased relative to BL following 1 min OCC (BL: 90 ± 3%, reperfusion: 85 ± 3%, P &lt; 0.05) and 5 min OCC (BL: 87 ± 3, reperfusion: 29 ± 3%, P &lt; 0.05). Thus during reperfusion the percentage of capillaries supporting RBC flux neither exceeded nor even returned to BL levels up to 5 min post OCC thereby demonstrating impaired capillary function and thus blood‐myocyte O2 and substrate flux. Consequently, the PORH state in the spinotrapezius muscle of the rat differs markedly from physiological contraction‐induced hyperemia found in humans.Grants: NIH HL‐108328 NIH T32OD011169

Exercise Mitigates Hyperhomocysteinemia Induced Vascular Dysfunction and Adverse Skeletal Muscle Remodeling

IntroHyperhomocysteinemia (HHcy) is associated with vascular and skeletal muscle dysfunction. HHcy induces MMP‐9 activity, myostatin release, systemic inflammation and may increase M1 macrophages. Previous reports suggest that exercise reduces HHcy and myostatin levels, however the effects of exercise on macrophages and myostatin during HHcy are unclear. We hypothesize that exercise decreases HHcy induced inflammation and muscular dysfunction by decreasing MMP‐9, myostatin and M1 macrophages.MethodsC57 WT, FVB, MMP‐9‐/‐, CBS‐/+ (HHcy), and CBS‐/+/MMP‐9‐/‐ (Double KO) mice were administered 4 weeks of treadmill running, swimming, or no exercise for controls. Ultrasonography and laser Doppler were used to measure wall to lumen ratio, blood flow and perfusion rate of the femoral artery. Western Blotting, IHC, Histology and PCR were used to analyze mouse tissue samples.ResultsBlood flow rates in control CBS‐/+ mice were approximately 23.9% lower than in control C57 WT mice. This rate was increased by 1.89 fold with exercise. Wall to Lumen ratio was approximately 4.14 fold higher in the CBS‐/+ control mice compared with WT, but became similar to WT after exercise. Laser Perfusion imaging demonstrated a 12.5% lower femoral artery red blood cell flux in CBS‐/+ mice when compared with WT, but was increased by 1.35 fold after exercise. Collagen staining reveals higher collagen deposition in the gastrocnemius of CBS‐/+ mice compared with WT, but was completely reversed with exercise.ConclusionsWe conclude that Exercise Mitigates HHcy Induced Vascular Dysfunction and Adverse Skeletal Muscle Remodeling.

Potassium Channels Mediate Hydrogen Sulfide‐induced Cutaneous Vasodilation in Healthy Young Adults

Preclinical models of cardiovascular disease suggest that hydrogen sulfide (H2S) is an endothelium‐derived hyperpolarizing factor that modulates vascular function via potassium (K+) channel activation. Exogenous H2S donors elicit cutaneous vasodilation in young adults; however, the specific mechanism(s) underlying H2S‐induced cutaneous vasodilation remain unclear. The aim of this study was to examinethe specific K+ channel(s) that mediate H2S‐induced vasodilation in the cutaneous circulation of healthy adults. Five microdialysis fibers were placed in the ventral forearm skin of 6 healthy adults (25 ± 3 yrs) for the local delivery of Ringers solution (control), 5 mM glybenclamide (GLY: KATP channel inhibitor), 1 mM senicapoc (SENI: KCa intermediate channel inhibitor), 50 mM tetraethylammonium (TEA: non‐specific KCa channel inhibitor) and GLY + SENI + TEA. Laser‐Doppler flowmetry was used to continuously measure red blood cell flux. After a stable baseline, 5 mM Na2S (fast‐acting H2S donor) was perfused through all fibers to elicit H2S‐induced vasodilation. Data were normalized to maximal cutaneous vascular conductance (%CVCmax = laser‐Doppler flux/ mean arterial pressure; 28 mM sodium nitroprusside) and expressed as a percentage increase from baseline. Na2S‐induced cutaneous vasodilation (Δbase 28±8 %CVCmax; P&lt;0.05). TEA (Δbase 4±3 %CVCmax) and GLY + SENI + TEA (Δbase 5±2 %CVCmax) blunted Na2S‐induced cutaneous vasodilation (both P&lt;0.05), whereas GLY (Δ base18±8 %CVCmax) or SENI alone (Δbase 22±7 %CVCmax) had no effect (both P&gt;0.05). These data suggest that exogenous H2S‐induced cutaneous vasodilation is mediated by TEA‐sensitiveKCa channels, but not by KATP or intermediate KCa channels, in healthy humans. NIH RO1 HL093238.