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Microvascular fluid exchange is primarily dependent on Starling forces and both the active and passive myogenic response of arterioles and post-capillary venules. Arterioles are classically considered resistance vessels, while venules are considered capacitance vessels with high distensibility and low tonic sympathetic stimulation at rest. However, few studies have investigated the effects of modulating interstitial hydrostatic pressure, particularly in the context of hemorrhagic shock. The objective of this study was to investigate the mechanics of arterioles and functional capillary density (FCD) during application of negative tissue interstitial pressure after 40% total blood volume hemorrhagic shock. In this study, we characterized systemic and microcirculatory hemodynamic parameters, including FCD, in hamsters instrumented with a dorsal window chamber and a custom-designed negative pressure application device via intravital microscopy. In large arterioles, application of negative pressure after hemorrhagic shock resulted in a 13 ± 11% decrease in flow compared with only a 7 ± 9% decrease in flow after hemorrhagic shock alone after 90 minutes. In post-capillary venules, however, application of negative pressure after hemorrhagic shock resulted in a 31 ± 4% decrease in flow compared with only an 8 ± 5% decrease in flow after hemorrhagic shock alone after 90 minutes. Normalized FCD was observed to significantly improve after application of negative pressure after hemorrhagic shock (0.66 ± 0.02) compared to hemorrhagic shock without application of negative pressure (0.50 ± 0.04). Our study demonstrates that application of negative pressure acutely improves FCD during hemorrhagic shock, though it does not normalize FCD. These results suggest that by increasing the hydrostatic pressure gradient between the microvasculature and interstitium, microvascular perfusion can be transiently restored in the absence of volume resuscitation. This study has significant clinical implications, particularly in negative pressure wound therapy, and offers an alternative mechanism to improve microvascular perfusion during hypovolemic shock.

Background: Non‐pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. Methods: Ocular surface microcirculation in small tissue volumes (~0.1 mm3) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. Results: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. Conclusion: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets. [ABSTRACT FROM AUTHOR]

Abstract Microvascular fluid exchange is primarily dependent on Starling forces and both the active and passive myogenic response of arterioles and post‐capillary venules. Arterioles are classically considered resistance vessels, while venules are considered capacitance vessels with high distensibility and low tonic sympathetic stimulation at rest. However, few studies have investigated the effects of modulating interstitial hydrostatic pressure, particularly in the context of hemorrhagic shock. The objective of this study was to investigate the mechanics of arterioles and functional capillary density (FCD) during application of negative tissue interstitial pressure after 40% total blood volume hemorrhagic shock. In this study, we characterized systemic and microcirculatory hemodynamic parameters, including FCD, in hamsters instrumented with a dorsal window chamber and a custom‐designed negative pressure application device via intravital microscopy. In large arterioles, application of negative pressure after hemorrhagic shock resulted in a 13 ± 11% decrease in flow compared with only a 7 ± 9% decrease in flow after hemorrhagic shock alone after 90 minutes. In post‐capillary venules, however, application of negative pressure after hemorrhagic shock resulted in a 31 ± 4% decrease in flow compared with only an 8 ± 5% decrease in flow after hemorrhagic shock alone after 90 minutes. Normalized FCD was observed to significantly improve after application of negative pressure after hemorrhagic shock (0.66 ± 0.02) compared to hemorrhagic shock without application of negative pressure (0.50 ± 0.04). Our study demonstrates that application of negative pressure acutely improves FCD during hemorrhagic shock, though it does not normalize FCD. These results suggest that by increasing the hydrostatic pressure gradient between the microvasculature and interstitium, microvascular perfusion can be transiently restored in the absence of volume resuscitation. This study has significant clinical implications, particularly in negative pressure wound therapy, and offers an alternative mechanism to improve microvascular perfusion during hypovolemic shock.

Objectives The purpose of this study was to model how CD variability affects tissue oxygenation under resting and exercise conditions. Additionally, we examine how CD impacts glucose and insulin transport in skeletal muscle. Methods We applied an established 3D finite difference model of oxygen transport to predict tissue oxygenation using FCD, hemodynamics, and SO2 measurements from a previous study. A 2D finite element model of glucose transport was applied to predict glucose and insulin uptake in PP and fasting conditions using the same range of CD. Results Control simulations used CD ranging from 562.5 to 781.3 capillaries/mm2, whereas prediabetic densities ranged from 375.0 to 593.8 capillaries/mm2. Mean tissue PO2 was 30.6±4.6 to 40.5±3.6 mm Hg for rest and 19.6±6.7 to 33.27±4.7 mm Hg for control and prediabetic simulations, respectively. Mean PP glucose concentrations were 5.85±1.13 mmol/L in the control group and 5.11±1.28 in the prediabetic simulations. Glucose uptake rates were 35% lower in the lowest capillary CD case compared to the high CD simulation. Conclusions Our simulations predict that CD decreases can have a substantial effect on oxygen delivery and glucose disposal across the observed physiological ranges of capillarization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation. Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development. OBJECTIVE: The goal of this study was to investigate the impact of experimental CBD treatment on early pancreatic inflammation in T1D by intravital microscopy (IVM) in NOD mice. METHODS: Seven-week-old female NOD mice were prophylactically administered daily 5 mg/kg CBD or control vehicle i.p. five times weekly for ten weeks. Animals underwent IVM following confirmation of T1D diagnosis by blood glucose testing. Leukocyte activation and functional capillary density (FCD) were quantified via IVM. RESULTS: CBD-treated NOD mice developed T1D later and showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation. CONCLUSIONS: Experimental CBD treatment reduced markers of inflammation in the microcirculation of the pancreas studied by intravital microscopy. [ABSTRACT FROM AUTHOR]

Objectives To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport. Methods A computational model was applied to capillary networks with dimensions 84 × 168 × 342 ( NI) and 70 × 157 × 268 ( NII) μm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis. Results A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3-4 fold. Conclusions These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis. [ABSTRACT FROM AUTHOR]

The choice of volume expander for fluid resuscitation in hemorrhagic shock is still debated. Changes in plasma viscosity (PV) are barely investigated while PV modulates functional capillary density, microcirculation and organ function. The present study evaluated the impact of 2 strategies of fluid resuscitation in hemorrhagic shock in pigs. Ten pigs were subjected to hemorrhagic shock and randomly assigned to a low viscosity fluid regimen (Lactated Ringer's, LR) group or a high viscosity regimen (hypertonic-hydroxyethyl starch, HES) for volume resuscitation. Sublingual microcirculatory flow and tissue oxygen tension were assessed together with macro- and microcirculatory, biochemical and rheological variables at baseline, 30 minutes after hemorrhagic shock, immediately after reaching resuscitation endpoints (R-0), and 60 minutes after resuscitation (R-60). PV decreased similarly in both groups following resuscitation (from 1.36 [1.32-1.38] to 1.21 [1.21-1.23] for LR, and from 1.32 [1.31-1.32] to 1.20 [1.17-1.21] mPa.s for HES). No differences were found between the groups for other rheological variables, microcirculatory flow or tissue oxygen tension at R-0 and R-60. Despite a 6-fold difference in the volumes required to achieve blood flow endpoints, commercially available volume expanders had similar effects on rheological and microcirculatory variables, irrespective of their viscosity. Our findings are consistent with the absence of clinically relevant differences between crystalloid and colloid resuscitation of hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Purpose: To identify associations between long-term (1 year) food intake and skin nutritive microvascular function in healthy subjects. Methods: This was a cross-sectional study. A validated 88-item food-frequency questionnaire was administered to 39 healthy men aged 23.4 ± 0.5 years and body mass index 23.3 ± 2.3 kg/m, who reported food intake during the last year and underwent videocapillaroscopy exams. The main outcome was the increase in functional capillary recruitment, that is, peak capillary density after post-occlusive reactive hyperemia subtracted from basal capillary density (caps/mm). Associations between reported food intake and functional capillary recruitment were investigated. Results: Daily average estimates of intake were: total energy (3,745 ± 1,365 kcal), carbohydrates (60.1 ± 5.9 %), lipids (22.1 ± 4.4 %), proteins (17.8 ± 4.1 %), fibers (33.9 ± 18.5 g), and cholesterol (492.8 ± 209.6 mg). Positive significant correlations with capillary recruitment were found for selenium (as μg/day/1,000 kcal; rho = 0.3412, p = 0.038,) calcium (as mg/day/1,000 kcal; rho = 0.3390, p = 0.043), and percentage of total energy from dairy products (rho = 0.3660, p = 0.023). Conclusions: Long-term intakes of selenium, calcium, and dairy products were positively associated with capillary recruitment in skin nutritive microcirculation in healthy young men. The role of such dietary components is discussed and possible mechanisms for their effects should be further investigated. This evidence adds one more possible functional property of these nutrients and food items. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Lumbricus terrestris (earthworm) erythrocruorin (LtEc) is a naturally occurring extracellular hemoglobin (Hb) with high molecular weight (3.6MDa), low autoxidation rate, and limited nitric oxide (NO) dioxygenation activity. These properties make LtEc a potential candidate for use as red blood cell (RBC) substitute, i.e. Hb-based oxygen carrier (HBOC). Previous studies have shown that small amounts of LtEc can be safely transfused into mice, rats, and hamsters without eliciting major side effects. Therefore, this study was designed to understand oxygen (O2) transport to tissues and systemic/microvascular hemodynamics induced by LtEc during anemic conditions. Main methods: Hamsters fitted with dorsal window chambers were hemodiluted to 18% hematocrit (Hct) using 6g/dL dextran 70kDa (Dex70). Hemodilution was then continued to 11% Hct using 10g/dL LtEc, 6g/dL Dex70 or 10g/dL human serum albumin (HSA). Blood pressure, heart rate, blood gas parameters, microvascular hemodynamics, microvascular blood flow, functional capillary density (FCD), intravascular pO2 and perivascular pO2 were studied. Key findings: LtEc maintained blood pressure without inducing vasoconstriction while increasing microvascular perfusion and FCD relative to Dex70 and HSA. LtEc increased blood O2 carrying capacity and maintained systemic and microvascular parameters without decreasing arteriolar diameter or increasing vascular resistance with during extreme anemia. LtEc increased O2 delivery compared to conventional plasma expanders. Significance: LtEc or synthetic molecules that replicate the characteristics of LtEc could be effective O2 carriers with potential to be used in transfusion medicine to prevent tissue anoxia resulting from severe anemia. [Copyright &y& Elsevier]

We have developed a novel mapping software package to reconstruct microvascular networks in three dimensions (3-D) from in vivo video images for use in blood flow and O2 transport modeling. An intravital optical imaging system was used to collect video sequences of blood flow in microvessels at different depths in the tissue. Functional images of vessels were produced from the video sequences and were processed using automated edge tracking software to yield location and geometry data for construction of the 3-D network. The same video sequences were analyzed for hemodynamic and O2 saturation data from individual capillaries in the network. Simple user-driven commands allowed the connection of vessel segments at bifurcations, and semiautomated registration enabled the tracking of vessels across multiple focal planes and fields of view. The reconstructed networks can be rotated and manipulated in 3-D to verify vessel connections and continuity. Hemodynamic and O2 saturation measurements made in vivo can be indexed to corresponding vessels and visualized using colorized maps of the vascular geometry. Vessels in each reconstruction are saved as text-based files that can be easily imported into flow or O2 transport models with complete geometry, hemodynamic, and O2 transport conditions. The results of digital morphometric analysis of seven microvascular networks showed mean capillary diameters and overall capillary density consistent with previous findings using histology and corrosion cast techniques. The described mapping software is a valuable tool for the quantification of in vivo microvascular geometry, hemodynamics, and oxygenation, thus providing rich data sets for experiment-based computational models. [ABSTRACT FROM AUTHOR]